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CAS No. : | 821-41-0 | MDL No. : | MFCD00002981 |
Formula : | C6H12O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | UIZVMOZAXAMASY-UHFFFAOYSA-N |
M.W : | 100.16 | Pubchem ID : | 69963 |
Synonyms : |
|
Num. heavy atoms : | 7 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.67 |
Num. rotatable bonds : | 4 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 31.64 |
TPSA : | 20.23 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.95 cm/s |
Log Po/w (iLOGP) : | 1.94 |
Log Po/w (XLOGP3) : | 1.36 |
Log Po/w (WLOGP) : | 1.33 |
Log Po/w (MLOGP) : | 1.39 |
Log Po/w (SILICOS-IT) : | 1.27 |
Consensus Log Po/w : | 1.46 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.05 |
Solubility : | 8.85 mg/ml ; 0.0884 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.39 |
Solubility : | 4.11 mg/ml ; 0.041 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.29 |
Solubility : | 5.12 mg/ml ; 0.0512 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.39 |
Signal Word: | Danger | Class: | 3 |
Precautionary Statements: | P210-P403+P235 | UN#: | 1987 |
Hazard Statements: | H225 | Packing Group: | Ⅲ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | for 5 h; Cooling with ice | Reference Example 4 [Synthesis of 1-bromo-5-hexene (7)] DMF (400 ml) was added to a 500 ml-capacity three neck flask containing a stirring bar and then was stirred while the flask was placed in an ice bath. Then, PBr3 (19.3 ml, 20 mmol) was dropped into the flask. When a milky-white precipitate was generated, the mixture was further manually stirred for 1 hour. Thereafter, 1-hexene-6-ol (14) (20 g, 20 mmol) was added to the mixture, which was then stirred for 5 hours. When generation of bromide was recognized by thin-layer chromatography, an aqueous sodium hydroxide solution was added to the mixture to stop the reaction. An organic layer was extracted with hexane, dried over Na2SO4, and filtered, and the solvent was distilled off under reduced pressure. Then, the organic layer was purified by flash chromatography on silica gel (hexane). Thus, 1-bromo-5-hexene (7) (8.48 g, 5 mmol, yield: 26percent) was obtained. 1HNMR values of the 1-bromo-5-hexene (7) are shown below. 1H NMR values of 1-bromo-5-hexene (7): 1H NMR (400 MHz, CDCl3) δ = 5.78 (ddt, 1H J1 = 8.8 Hz, J2 =18.8 Hz, J3 = 25.6 Hz), 4.97 (m, 2H), 3.38 (t, 2H, J = 6.8 Hz), 2.08 (m, 2H), 1.86 (m, 2H), 1.52 (m, 2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With [bis(acetoxy)iodo]benzene; pyridine hydrochloride In dichloromethane at 20℃; for 6h; | |
65% | With aluminum (III) chloride; oxygen; vanadium(V) oxytriisopropoxide; tetra-(n-butyl)ammonium iodide In acetonitrile at 80℃; for 24h; | General procedure for vanadium-catalyzed chlorination underatmospheric molecular oxygen General procedure: In a 5 mL three-necked flask, Bu4NI (111 mg, 0.3 mmol), AlCl3(40 mg, 0.3 mmol), and VO(OiPr)3 (15 μL, 0.063 mmol) were placed. The flask was evacuated and backfilled with molecular oxygen. To the mixture, acetonitrile (1 mL) and a substrate (0.25 mmol) were added. The mixture was stirred at 80 °C under atmospheric molecular oxygen,followed by treatment with 1:1 mixture of saturated Na2S2O3 aqueous solution and saturated NaHCO3 aqueous solution, and extraction with ether. The organic layer was dried over MgSO4, filtered, and evaporated. 1,3,5-Trimethoxybenzene or 1,2,4,5-tetramethylbenzene was added as an internal standard, and 1H NMR analysis was performed to determine an NMR yield. Spectral data of the products were identical with those of commercially available and authentic samples |
56% | With manganese(II) chloride tetrahydrate; 1,1,1,2-tetrachoroethane; N,N,N,N-tetraethylammonium tetrafluoroborate In acetonitrile at 50℃; Electrolysis; Inert atmosphere; |
With sodium hypochlorite; potassium dihydrogenphosphate In water at 5℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With [bis(acetoxy)iodo]benzene; Pyridine hydrobromide In dichloromethane at 20℃; for 6h; | |
94% | With ammonium metavanadate; tetrabutylammomium bromide; trifluoroacetic acid In 1,4-dioxane at 80℃; for 12h; | |
94% | With ammonium cerium (IV) nitrate; dihydrogen peroxide; lithium bromide In water at 65 - 70℃; for 5h; |
43% | With tris(2,2'-bipyridyl)ruthenium dichloride; carbon tetrabromide In acetonitrile at 20℃; for 72h; Irradiation; | General procedure for the bromination of phenols and alkenes General procedure: To a 10 mL round bottom flask equipped with a magnetic stir bar were added phenols or alkenes (0.1 mmol), CBr4 (33 mg, 0.1 mmol), dry CH3CN (1 mL) and Ru(bpy)3Cl2 (3.8 mg, 0.005 mmol). The mixture was irradiated with blue LEDs (1 W) at room temperature open to air until the starting material disappeared completely (monitored by TLC). After the reaction was completed, the solvent was concentrated in vacuo. The residue was purified by flash column chromatography to give the final product. |
With bromine In diethyl ether at 0℃; | ||
With bromine In dichloromethane at -20℃; | ||
With bromine In diethyl ether at 20℃; | ||
With bromine In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere; | ||
70 %Spectr. | With tetrabutylammomium bromide; dihydrogen peroxide; trifluoroacetic acid In dichloromethane; water at 25℃; for 12h; Inert atmosphere; | 2. General procedure for oxidative bromination reaction General procedure: In a 10 mL two-necked flask equipped with a reflux condenser, substrate (0.25mmol) and tetrabutylammonium bromide (161.2 mg, 0.50 mmol) were placed. The flaskwas evacuated and backfilled with Ar. To the mixture, an ultrapure water (0.5 mL),trifluoroacetic acid (57.5 μL, 0.75 mmol), and 30% H2O2 (77 μL, 0.75 mmol) wereadded. The mixture was stirred at 25 °C under Ar, followed by treatment with 1:1mixture of saturated Na2S2O3 aqueous solution and saturated NaHCO3 aqueous solution,and extraction with ether. The organic layer was dried over Na2SO4, filtered, andevaporated. 1,3,5-Trimethoxybenzene or hexamethylbenzene was added as an internalstandard, and 1H NMR analysis was performed to determine a NMR yield. Spectral dataof the products were identical with those of commercially available and authenticsamples. |
With bromine In dichloromethane at 0℃; | 21.a; 54.a a. 5,6-Dibromo-hexan-1-ol To an ice bath cooled solution of 5-hexen-1-ol (11.23 g, 112.3 mmol) in about 20 ml methylene chloride was added bromine (5.80 ml plus 12 drops, 112.3+mmol) in about 20 ml methylene chloride. At the completion of the addition, the mixture is dried in vacuo to yield 29.1 g of 5,6-dibromo-hexan-1-ol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine In dichloromethane at 20℃; for 1h; | |
100% | With triethylamine In dichloromethane at -15℃; for 1h; Green chemistry; | |
100% | With triethylamine In dichloromethane at -15℃; for 1.5h; |
100% | With triethylamine In tetrahydrofuran at 0 - 20℃; for 0.5h; | 4.3. 6-Phenylhex-5-en-1-yl methanesulfonate (10a)7 General procedure: To a solution of 9a (5.85 g, 33 mmol) and Et3N (5.85 mL, 42 mmol) in THF (95 mL) was added MsCl (2.6 mL, 33.6 mmol) at 0 °C, and the mixture was stirred at room temperature for 2 h. The reaction was quenched with water (84 mL), and the separated aqueous layer was extracted with EtOAc (150 + 75 + 75 mL). The combined organic layers were washed with 10% HCl aq (50 mL), satd NaHCO3 aq (50 mL), brine (50 mL), dried over Na2SO4, and concentrated. Column chromatography (SiO2 200 g, hexane/EtOAc 4/1 to 3/2) gave 10a (7.77 g, E/Z 9/1, 93%) as a colorless oil. |
99% | With pyridine In dichloromethane for 2h; Ambient temperature; | |
99% | With triethylamine In dichloromethane for 1h; Cooling with ice; | |
99% | With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere; Cooling with ice; | Procedure C: Mesylation of alcohols General procedure: To an ice cooled 0.12 M solution of alcohol in DCM containing NEt3 (7.0 equiv) and DMAP (0.1 equiv)was added MsCl (2.4 equiv) dropwise. The solution was stirred for 30 minutes before being allowed to warm to room temperature; it was then stirred at room temperature until completion. The reaction was quenched by the slow addition of water. The layers were separated and the aqueous one was extracted three times with DCM; the combined organics were washed with aq. 1M KHSO4, sat. aq. NaHCO3 and brine before being dried over MgSO4 and concentrated under reduced pressure. The resulting crude product was then purified through column chromatography. |
99% | With dmap; triethylamine In dichloromethane at 0 - 20℃; | |
98% | With triethylamine Inert atmosphere; | |
96% | With triethylamine In dichloromethane at 0℃; Inert atmosphere; | 1-Methanesulfonyloxyhexa-5-ene (1a) To a solution of 5-hexene-1ol (2.4 mL, 20.4 mmol) and triethylamine (4.3mL) in 80 mL of dry CH2Cl2 was added dropwise methanesufonyl chloride (1.75 mL, 22.6 mmol) at 0 °C under N2 atomosphere. After completion of addition, the reaction mixture was poured into water (200 mL). The organic phase was washed with 1N HCl, saturated NaHCO3 aqueous solution, and brine in the order. The organic phase was separated , dried with MgSO4 , and evaporated to leave a residue. The resulting colorless liquid (3.51 g, 96%) was used for nexst step without further purification. |
92% | With triethylamine In ethyl acetate at -10 - 20℃; for 12h; | 8.c 8c) 86.1 g (752 mmol) of methanesulfonyl chloride are slowly added with stirring to a cold (-10° C.) solution of 62.0 g (619 mmol) of hex-5-en-1-ol and 101.44 g (1003 mmol) of triethylamine in 1000 ml of ethyl acetate in a 2 litre flask at such a rate that the internal temperature remains below 5° C. The suspension is stirred at room temperature for 12 hours. The salt, triethylammonium chloride, is filtered off and washed a number of times with ethyl acetate. The combined filtrates are evaporated to about 600 ml and washed with 75 ml of 10% hydrochloric acid, with 50 ml of saturated sodium hydrogencarbonate solution and with 50 ml of saturated sodium chloride solution. The organic phase is freed from solvent in a rotary evaporator, taken up in 500 ml of dichloromethane and dried using MgSO4. The mixture is then filtered, dichloromethane is evaporated, and the residue is subjected to fractional distillation in vacuo (boiling point: 80° C./3·10-3 mbar). 101.2 g of liquid 1-mesylhex-5-ene are obtained. The yield of 1-mesylhex-5-ene is 92%, based on hex-5-en-1-ol. The product, 1-mesylhex-5-ene, is characterised by means of the 1H-NMR spectrum.1H-NMR (CD3CN, reference substance: TMS), δ, ppm: 1.43-1.53 m (CH2), 1.67-1.77 m (CH2), 2.05-2.13 q (CH2), 3.00 s (CH3), 4.20 t (CH2); 3JH,H=6.5 Hz, 4.97 d,m (1H; cis-H, H2CCH-), 5.04 d,m (1 H; trans-H, H2CCH-), 5.84 d,d,t (1H); 3JH,H=6.8 Hz, 3JH,H=10.3 Hz, 3JH,H=17.0 Hz.This spectrum is identical to the spectrum of 1-mesylhex-5-ene described in the literature (O. Phanstiel et al., J. Med. Chem., Vol. 48, 2005, pp. 3832-3839). |
91% | With pyridine In dichloromethane at 20℃; for 24h; | |
89% | With triethylamine In dichloromethane at 0 - 25℃; for 95h; Inert atmosphere; | |
83% | With triethylamine In dichloromethane for 1h; | |
81% | With pyridine | |
72% | Stage #1: 5-Hexen-1-ol With triethylamine In N,N-dimethyl-formamide for 0.166667h; Inert atmosphere; Stage #2: methanesulfonyl chloride In N,N-dimethyl-formamide at 20℃; for 48h; Inert atmosphere; | 48 5-Hexenol (6.0 mL, 50.5 mmol) and sodium azide (17g, 252.5 mmol) were dissolved in DMF (120 mL). To this solution tiethylamine (14 mL, 151.5 mmol) was added. The reaction mixture stuffed under argon for 10 minutes. Then methanesulfonyl chloride (4.25mL, 50.Smmol) was added to the solution dropwise over 20 minutes. Stirring was continued under argon at room temperature for 2 days. The reaction mixture was decanted into iced water, which was then washed with 5 x 50 mL portions of diethyl ether. The organic layer was dried over sodium sulfate, filtered and evaporated to dryness, to afford crude compound 134 (Rf = 0.67 in 5% MeOH/DCM, 6.Og). Purification of compound 134 by column chromatography by first eluting with dichioromethane to remove impurities followed by 2%methanol/dichloromethane afforded 4.6g (72%) of a clear liquid. ‘H NMR (400 MHz, DMSOd 6): ö 5.78 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 5.16 - 4.74 (m, 2H), 2.68 - 2.14 (m, 2H), 1.64 -1.27 (m, 4H), 1.24 - 0.92 (m, 2H) |
With pyridine | ||
With pyridine | ||
With triethylamine In dichloromethane | ||
With triethylamine In dichloromethane for 2h; | ||
With triethylamine In dichloromethane for 2h; | ||
With triethylamine In dichloromethane at 0 - 20℃; for 25h; | ||
In dichloromethane at 0℃; | ||
With triethylamine In dichloromethane at 20℃; | ||
With triethylamine In dichloromethane | ||
With triethylamine In dichloromethane at 0℃; for 1h; | ||
With triethylamine In dichloromethane at -5 - 20℃; for 3h; | ||
Stage #1: 5-Hexen-1-ol With triethylamine In dichloromethane at -5℃; for 0.5h; Inert atmosphere; Stage #2: methanesulfonyl chloride In dichloromethane at -10 - -5℃; for 1h; Inert atmosphere; | ||
With triethylamine In dichloromethane | ||
With triethylamine In dichloromethane at 0 - 20℃; for 3h; | To a solution of 5-hexen-1-ol (3.50 mL, 29.0 mmol) and NEt3 (5.25 ml, 37.7 mmol) in dryCH2Cl2 (70 mL) at 0 °C was added methanesulfonyl chloride (2.45 mL, 31.9 mmol)dropwise. The resulting solution was stirred for 3 h at RT. Reaction was quenched withwater (100 mL) and extracted with CH2Cl2 (3 x 100 mL). The combined organic extracts were washed with saturated NH4Cl solution, brine, dried (MgSO4), filtered andconcentrated in vacuo to provide 5.61g of crude mesylate product.To a solution of 6-((triisopropylsilyl)oxy)hexan-1-ol S1 (13.0 g, 47.5 mmol) in dry THF(130 mL) at 0 °C was added sodium hydride (1.90 g of 60% dispersion in mineral oil, 47.5mmol) portionwise and the mixture allowed to warm to RT over 30 min. A solution of thecrude mesylate in dry THF (20 mL) was then added and the mixture heated to refluxovernight. Reaction was quenched with water (100 mL) and extracted with Et2O (3 x 100mL). The combined organic extracts were washed with brine, dried (MgSO4), filtered andconcentrated in vacuo Purification by flash column chromatography (Hexane then 4%Et2O/Hexane) provided alkene 8 (6.17 g, 91%), as a colourless oil. Further elution with50% Et2O/Hexane provided 5.68 g of unreacted 6-((triisopropylsilyl)oxy)hexan-1-ol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With toluene-4-sulfonic acid In dichloromethane for 3h; | |
95% | With pyridinium 4-toluenesulfonate In dichloromethane at 25℃; for 0.5h; Inert atmosphere; | |
93% | In dichloromethane at 20℃; for 2h; |
92% | With sulfuric acid for 3h; Ambient temperature; | |
90% | With pyridinium 4-toluenesulfonate In dichloromethane for 20h; Ambient temperature; | |
77% | With BINOL H; diphenyldisulfane In dichloromethane at 20℃; for 6h; Schlenk technique; Irradiation; Inert atmosphere; | 3. General Procedure for BINOL-Catalyzed Acetalization underVisible Light General procedure: To an oven-dried round-bottom Schlenk tube (10 mL) with a magnetic stir bar, 3,4-dihydro-2H-pyran (0.101 g, 0.6 mmol, 1.2 eq) and 3-phenyl-1-propanol(0.068 g, 0.5mmol, 1.0 equiv.), BINOL H (3.10 mg, 10 μmol, 0.01 equiv.), PhSSPh (2.20 mg, 10 μmol,0.02 equiv.) and dry dichloromethane (0.50 mL) were added and the mixture wasallowed to irradiate under purple LEDs reactor (6 W,λmax 400 nm)(followed by TLC).The pure products were purified by column chromatography (SiO2, hexane: ethylacetate=15 :1). |
58% | With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; for 2h; | |
With pyridinium 4-toluenesulfonate In dichloromethane | ||
With pyridinium 4-toluenesulfonate In dichloromethane at 20℃; for 2h; Inert atmosphere; | ||
With toluene-4-sulfonic acid | 29 First, a compound represented by the following formula (42) was synthesized using 5-hexen-1-ol, 3,4-dihydro-2H-pyran and p-toluenesulfonic acid. Furthermore, the epoxy compound represented by the following formula (43) was synthesized by oxidizing the compound represented by the formula (42) using metachloroperbenzoic acid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With air; potassium carbonate In water at 46.84℃; for 24h; | |
80% | With Oxone; 2-Iodobenzoic acid In water; acetonitrile at 70℃; for 6h; | |
76.6% | With chromic acid In water; acetone < 5 deg C; |
67% | With jones reagent In acetone for 0.5h; Ambient temperature; | |
61% | With dipyridinium dichromate In N,N-dimethyl-formamide at 20℃; for 7h; | |
60% | With chromium(VI) oxide In sulfuric acid; acetone at 5℃; for 8h; | |
54% | With sulfuric acid; chromium(VI) oxide In water; acetone at -5℃; for 12.5h; Inert atmosphere; | Hex-5-enoic acid (28) To a stirred solution of chromium trioxide (11.23 g, 112 mmol) in aqueous sulfuricacid (2M, 134 mL, 270 mmol) at -5 °C was added 5-hexen-1-ol (3.0 g, 29.5 mmol) in acetone (100 mL) over30 min. The resulting black suspension was stirred for 12 h at -5 °C. Thereafter, the reaction mixture wasdiluted with diethyl ether (100 mL) and the layers were separated. The organic layer was washed withaqueous NaOH solution (1M, 2 × 35 mL) and again the layers were separated. The combined aqueous layerswere acidified with sulfuric acid (6M, 20 mL), and then extracted with diethyl ether (3 × 25 mL). Thecombined organic layers were washed with saturated NaCl solution (15 mL), dried over Na2SO4, filtered,and concentrated under reduced pressure. The crude acid was purified by flash chromatography(petroleum ether/ethyl acetate, 7:3) to give acid 28 (1.85 g, 54%) as a colorless liquid. Rf = 0.26 (petroleumether/ethyl acetate, 8:2); 1H NMR (400 MHz, CDCl3): δ = 1.73 (tt, apparent q, J = 7.5 Hz, 2H, 3-H), 2.12 (m,2H, 4-H), 2.38 (t, J = 7.5 Hz, 2H, 2-H), 5.01-5.08 (m, 2H, 6-H), 5.77 (ddt, J = 17.0, 10.2, 6.7 Hz, 1H, 5-H); 13CNMR (100 MHz, CDCl3): δ = 23.7 (C-3), 32.9 (C-4), 33.1 (C-2), 115.2 (C-6), 137.5 (C-5), 179.3 (C-1). |
In water; acetone | 5-Hexenoic acid (1-2) 5-Hexenoic acid (1-2) A solution of 5-hexene-1-ol (Aldrich, 25 g, 0.25 mol) in acetone (1 L) was cooled to 0° C. and treated with a quantity of Jones reagent sufficient to obtain a persistent orange solution (~150 mL). The excess reagent was quenched with isopropyl alcohol and the solvents were removed in vacuo. The greenish residue was dissolved in H2 O and extracted with EtOAc. The EtOAc layer was washed with 10% KHSO4 solution, brine, dried with MgSO4, filtered and carefully evaporated in the absence of external heat to give 1-2 as a clear oil. 1 H NMR (400 MHz, CDCl3) δ5.8 (m, 1H), 5.0 (m, 2H), 2.38 (t, 2H), 2.10 (m, 2H), 1.75 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With [2-percarboxyethyl] functionalized silica In dichloromethane at 20℃; for 1h; | |
86% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; | |
85% | With 3-chloro-benzenecarboperoxoic acid In water for 2h; |
76% | With 3-chloro-benzenecarboperoxoic acid | |
76% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane at -2 - 27℃; for 16h; Inert atmosphere; | |
72% | With 3H-2,1-benzoxaselenole Se-oxide; dihydrogen peroxide; magnesium sulfate; trifluoroacetic acid In dichloromethane at 20℃; for 2h; | |
62% | With dihydrogen peroxide; sodium carbonate; dicyclohexyl-carbodiimide In methanol; water | |
50% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; | |
10% | With dihydrogen peroxide; sodium acetate In methanol; water at 20℃; for 64h; pH=4.5; | |
38.5 % Turnov. | With iodosylbenzene In benzene for 3h; | |
With iodosylbenzene; [Ni(II)2(μ-L2)2](ClO4)2 In acetonitrile for 4h; Inert atmosphere; | ||
With 3-chloro-benzenecarboperoxoic acid | ||
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 14h; | ||
With dihydrogen peroxide; C36H30FeN10(3+)*2CF3O3S(1-)*F6P(1-) In acetonitrile at 20℃; for 2h; | 4.2. Catalytic procedures All reactions were conducted in a cryostat (Julabo FP-50) with atotal reaction volume of 4.0 mL. Acetonitrile (HPLC-grade) wasapplied as solvent for all experiments. The catalyst (1.0 mol%,2.69 mmol) was added from a preformed stock solution (4.0 mg/mL in acetonitrile) according to the appropriate stoichiometry toa solution of cis-cyclooctene (100 mol%, 269 mmol) and, if applied,the respective Brnsted/Lewis acid (0.1 mol%, 26.9 mmol) in acetonitrile.The reaction was started upon addition of H2O2(150 mol%, 403.5 mmol). The reaction was aborted by adding electrolyticallyprecipitated activated MnO2 as a H2O2 decompositionagent. After filtration over activated neutral alumina, two GC sampleswere prepared for each experiment using 200 lL filtrate,500 lL external standard (p-xylene, 4.0 mg/mL in i-PrOH) and800 lL n-hexane, respectively. Control experiments without catalystand additive were performed as a reference for all reactions.Evaluation of other substrates beside cis-cyclooctene was performedusing 1H NMR spectroscopy. Reactions were carried outat 20 C in a total volume of 1.0 mL with a catalyst concentrationof 0.5 mol% in doubled absolute concentrations. A stock solutionof the respective catalyst (2.04 mg mL1 in CD3CN) was added toa preformed solution of the respective substrate (100 mol%,134.5 mmol) in deuterated acetonitrile. The reaction was startedupon addition of H2O2 (150 mol%, 201.8 mmol) and aborted after2 h by addition of MnO2. The suspension was filtered and C6H6was added as an external standard. 1H NMR spectra were recordedfor each experiment and the products were quantified by the integralratios of the respective olefin, epoxide and cis diol protons. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With lithium aluminium hydride | |
51% | Stage #1: 5-hexenoic acid With phenylsilane; potassium-t-butoxide; C22H30ClN2RuS2(1+)*Cl(1-) In tetrahydrofuran at 60℃; for 18h; Inert atmosphere; Stage #2: With water monomer; caesium fluoride In tert-butyl methyl ether at 20℃; for 3h; Inert atmosphere; | Hex-5-en-1-ol (2o): To a stirred suspension of 5-hexenoicacid (1o) (500 mg, 4.3802 mmol,1equiv.) in degassed THF (10 V) was added ARP-03 (45.8 mg, 0.0876 mmol, 2 mol%)and again degassed for 10 minutes. After 10 minutes of degassing, PhSiH3 (1.63mL, 13.1406 mmol, 3 equiv.) and t-BuOK (1 M in THF) (0.43 mL, 0.438 mmol, 10mol%) were added dropwise to reaction mixture at RT. The reaction mixture washeated to 60°C and stirred for 18 h. The reaction mixture was then evaporatedto remove volatiles, then suspended in MTBE and stirred with aq. CsF solution(10%, 10 V) for 3 h. The organic layer was then separated and concentrated invacuum to furnish the crude, which was purified by columnchromatography on silica gel (eluent: Ethyl acetate / n-hexane = 0.5 / 4.5) toafford hex-5-en-1-ol (2o) (223 mg,51%) as a colourless oil.1H NMR (400 MHz, DMSO -d6): δ5.85 - 5.70 (m, 1H), 5.10 - 4.85 (m, 1H), 4.35 (t, J = 6 Hz, 1H), 3.45 - 3.30 (m, 2H), 2.10 - 1.90 (m, 2H), 1.50 -1.30 (m, 4H).13C NMR (100 MHz, DEPT -135, CDCl3): δ 138.62 (CH), 114.44 (CH2), 62.21 (CH2), 33.44 (CH2),31.99 (CH2), 25.01 (CH2). |
With hydrogen In aq. phosphate buffer at 50℃; for 48h; Autoclave; |
With lithium aluminium hydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | In dichloromethane at -78 - 20℃; for 1h; | 1.1. To a solution of hex-5-en-1-ol (30.9 g, 309 mmol) and DMAP (41.5 g, 340 mmol, 1. 1 equiv) in CH2C12 (750 mL, 0.4 M) at-78 DEG C, was added acetic anhydride (32.1 mL, 340 mmol, 1. 1 equiv). The reaction was stirred at rt for 1 h. The product was passed through a plug of silica gel using 20 % EA/Hex to afford the desired product (42.7 g, Yield = 97 %) as a colorless oil. |
97% | With dmap In dichloromethane at -78 - 20℃; for 1h; | 1.6 Step 6: 5,6-dibromohexyl acetate To a solution of hex-5-en-1-ol (30.9 g, 309 mmol) and DMAP (41.5 g, 340 mmol, 1. 1 equiv) in CH2C12 (750 mL, 0.4 M) at-78 C, was added acetic anhydride (32.1 mL, 340 mmol, 1.1 equiv). The reaction was stirred at rt for 1 h. The product was passed through a plug of silica gel using 20 % EA/Hex to afford the desired product (42.7 g, Yield = 97 %) as a colorless oil. The compound was used directly for bromination. To a solution of hex-5-en-lyl acetate (42.7g, 300 mmol) in CH2C12 (600 mL, 0.5 M) at-78 C, was added bromine (330 mL, 330 mmol, 1.1 equiv). The reaction was stirred at-78 C for 15 min then warmed to rt. The solvent was evaporated to afford the desired product (89 g, Yield = 98 %) as a yellowish oil.'H NMR (500 MHz, acetone-d6): 8 4.38-4. 32 (m, 1H), 4.04 (t, 2H), 3.95-3. 93 (m, 1H), 3.84-3. 80 (m, 1H), 2.16-2. 10 (m, 1H), 1. 98 (s, 3H), 1.90-1. 82 (m, 1H), 1.72-1. 62 (m, 3H), 1.56-1. 48 (m, 1H). |
85% | With pyridine Ambient temperature; |
With pyridine for 4h; Heating; | ||
With pyridine | ||
In pyridine | ||
With pyridine | ||
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 8h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: hex-5-en-1-ol With N,N,N-tributyl-1-butanaminium iodide; sodium hydride In tetrahydrofuran at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: benzyl bromide In tetrahydrofuran at 20℃; Inert atmosphere; | Preparation of ((pent-4-en-1-yloxy)methyl)benzene(5c) General procedure: To a dry round bottom flask under nitrogen was added 1.4 gof 60% NaH dispersion (0.834 g NaH, 34.5 mmol, 2eq.),followed by ~200 mg of tetrabutylammonium iodide. 18 mLof dry THF was added and the reaction was cooled to 0 °Cusing an ice bath. Pent-4-en-1-ol (1.5 g, 17.4 mmol, 1 eq.)was added dropwise. The reaction was stirred at 0 °C for5 min and then benzyl bromide (3.57 g, 21 mmol, 1.2 eq.)was added. The reaction was warmed to room temperatureand stirred overnight. The reaction was quenched with sat.NH4Cl (15 mL) and then extracted 3×10 mL diethyl ether.The combined organic layers were dried over Na2SO4, filteredand concentrated onto Celite under reduced pressure.The crude material was purified by flash chromatography(silica; ethyl acetate/hexanes, 0~5%). Percent yield: 100%. |
100% | Stage #1: hex-5-en-1-ol With N,N,N-tributyl-1-butanaminium iodide; sodium hydride In tetrahydrofuran at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: benzyl bromide In tetrahydrofuran at 20℃; Inert atmosphere; | Preparation of ((pent-4-en-1-yloxy)methyl)benzene(5c) General procedure: To a dry round bottom flask under nitrogen was added 1.4 gof 60% NaH dispersion (0.834 g NaH, 34.5 mmol, 2eq.),followed by ~200 mg of tetrabutylammonium iodide. 18 mLof dry THF was added and the reaction was cooled to 0 °Cusing an ice bath. Pent-4-en-1-ol (1.5 g, 17.4 mmol, 1 eq.)was added dropwise. The reaction was stirred at 0 °C for5 min and then benzyl bromide (3.57 g, 21 mmol, 1.2 eq.)was added. The reaction was warmed to room temperatureand stirred overnight. The reaction was quenched with sat.NH4Cl (15 mL) and then extracted 3×10 mL diethyl ether.The combined organic layers were dried over Na2SO4, filteredand concentrated onto Celite under reduced pressure.The crude material was purified by flash chromatography(silica; ethyl acetate/hexanes, 0~5%). Percent yield: 100%. |
98% | Stage #1: hex-5-en-1-ol With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.0833333h; Stage #2: benzyl bromide In tetrahydrofuran; mineral oil at 20℃; for 16h; |
98% | Stage #1: hex-5-en-1-ol With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.0833333h; Stage #2: benzyl bromide In tetrahydrofuran; mineral oil at 0 - 20℃; for 16h; | |
97% | Stage #1: hex-5-en-1-ol With sodium hydride In tetrahydrofuran at 20℃; Stage #2: benzyl bromide In tetrahydrofuran at 0 - 25℃; | |
97% | In tetrahydrofuran at 20℃; | |
96% | With sodium hydride In tetrahydrofuran at 20℃; for 3h; | |
96% | With sodium hydride In tetrahydrofuran at 0 - 20℃; for 3h; Inert atmosphere; | |
95% | With N,N,N-tributyl-1-butanaminium iodide; sodium hydride In N,N-dimethyl-formamide at 20℃; for 6h; | |
95% | With N,N,N-tributyl-1-butanaminium iodide; sodium hydride | |
95% | With sodium hydride In tetrahydrofuran at 0 - 20℃; for 3h; Inert atmosphere; | |
94% | Stage #1: hex-5-en-1-ol With N,N,N-tributyl-1-butanaminium iodide; sodium hydride In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: benzyl bromide In tetrahydrofuran at 0 - 20℃; | |
93% | With sodium hydride In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere; | |
92% | Stage #1: hex-5-en-1-ol With sodium hydride In tetrahydrofuran at 0 - 20℃; for 0.166667h; Reflux; Stage #2: benzyl bromide In tetrahydrofuran at 20℃; for 0.0833333h; Reflux; | |
89% | With sodium hydride In tetrahydrofuran at 20℃; Inert atmosphere; | |
86% | With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 16h; | |
85% | Stage #1: hex-5-en-1-ol With sodium hydride; sodium iodide In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: benzyl bromide In tetrahydrofuran at 20℃; Inert atmosphere; | |
78% | Stage #1: hex-5-en-1-ol With sodium hydride In mineral oil at 0℃; for 1h; Stage #2: benzyl bromide In tetrahydrofuran; mineral oil | |
With sodium hydride | ||
With sodium hydride In tetrahydrofuran | ||
With silver(I) oxide In N,N-dimethyl-formamide | ||
With sodium hydride In N,N-dimethyl-formamide | ||
With sodium hydride In tetrahydrofuran at 0 - 20℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 1H-imidazole In N,N-dimethyl-formamide | |
100% | With 1H-imidazole In tetrahydrofuran at 20℃; | 65.i 65. i. Tert-butyl-hex-5-enyloxy-dimethyl-silane To a solution of 5-hexen-1-ol (5 g, 50 mmol) in THF (80 mL) were sequentially added TBDMSCl (8.4 g, 55 mmol) and imidazole (4.01 g, 60 mmol). The mixture was stirred at rt overnight. Water was added and the two phases separated. The aq. phase was extracted with ether and the combined org. layers were dried over MgSO4 and concentrated to give the title intermediate as a colourless liquid (11.2 g, 100% yield). 1H NMR (CDCl3) δ: 5.81 (m, 1H), 4.98 (m, 2H), 3.61 (t, J=6.2 Hz, 2H), 2.06 (q, J=7.3 Hz, 2H), 1.48 (m, 4H), 0.90 (m, 9H), 0.07 (m, 6H). |
100% | With 1H-imidazole In dichloromethane at 20℃; for 19h; | 7.1.2.i To a stirred solution of 5-hexen-l-ol 807 (5.00 mL, 41.64 mmol) in CH2CI2 (150 mL) at r.t. was added imidazole (2.86 g, 43.06 mmol) and terf-butyldimethylsilyl chloride (6.34 g, 42.06 mmol). The reaction mixture was allowed to stir at r.t. for 19 h. The mixture was then diluted with EtOAc (400 mL), washed with water (200 mL) a nd brine (200 mL), dried over anhyd rous Na2S04 and concentrated in vacuo. The crude product was purified by flash column chromatography (petroleum ether) to give the title compound 808 (8.846 g, quant.) as a colourless oil. Rf 0.90 (petroleum ether-EtOAc 9: 1); δΗ (400 MHz; CDCb) 5.81 (1H, ddt, J = 17.1, 10.1, 6.7 Hz, H-5), 5.00 (1H, dq, J = 17.2, 1.7 Hz, Ha-6), 4.94 (1H, d, J = 10.5 Hz, Hb-6), 3.61 (2H, t, J = 6.2 Hz, H-l), 2.06 (2H, q, J = 7.1 Hz, H-4), 1.59-1.50 (2H, m, H-2), 1.47- 1.39 (2H, m, H-3), 0.89 (9H, s, SiC(CHj)s), 0.05 (6H, s, Si(CH3)2); c (100 MHz; CDCb) 139.0 (CH, C-5), 114.3 (CH2, C-6), 63.1 (CH2, C-l), 33.5 (CH2, C-4), 32.3 (CH2, C-2), 26.0 (3 x CH3, SiC(CH3)3), 25.2 (CH2, C-3), 18.4 (C, SiC(CH3)3), -5.3 (2 x CH3, Si(CH3)2). Spectroscopic data was consistent with that reported in literature. |
100% | With 1H-imidazole In tetrahydrofuran at 20℃; | 65.i Example 65: (RS)-3-(2,3-dihydro-benzo[l,4]dioxin-6-yl)-5-[4-(6-methoxy-quinazolin- 4-ylamino)-butyl]-oxazolidin-2-one:; 65. i. Tert-butyl-hex-5-enyloxy-dimethyl-silane:; To a solution of 5-hexen-l-ol (5 g, 50 mmol) in THF (8O mL) were sequentially added TBDMSCl (8.4 g, 55 mmol) and imidazole (4.01 g, 60 mmol). The mixture was stirred at rt overnight. Water was added and the two phases separated. The aq. phase was extracted with ether and the combined org. layers were dried over MgSO4 and concentrated to give the title intermediate as a colourless liquid (11.2 g, 100% yield).1H NMR (CDCl3) δ: 5.81 (m, IH), 4.98 (m, 2H), 3.61 (t, J = 6.2 Hz, 2H), 2.06 (q, J = 7.3 Hz, 2H), 1.48 (m, 4H), 0.90 (m, 9H), 0.07 (m, 6H). |
100% | With 1H-imidazole In dichloromethane at 20℃; for 19h; | 2.7.2.i Step i To a stirred solution of 5-hexen-l-ol 807 (5.00 mL, 41.64 mmol) in CH2CI2 (150 mL) at r.t. was added imidazole (2.86 g, 43.06 mmol) and terf-butyldimethylsilyl chloride (6.34 g, 42.06 mmol). The reaction mixture was allowed to stir at r.t. for 19 h. The mixture was then diluted with EtOAc (400 mL), washed with water (200 mL) and brine (200 mL), dried over anhyd rous Na2S04 and concentrated in vacuo. The crude product was purified by flash column chromatography (petroleum ether) to give 808 (8.846 g, quant.) as a colourless oil . (1254) Rf 0.90 (petroleum ether-EtOAc 9: 1); δΗ (400 MHz; CDC ) 5.81 (1H, ddt, J = 17.1, 10.1, 6.7 Hz, H-5), 5.00 (1H, dq, J = 17.2, 1.7 Hz, Ha-6), 4.94 (1 H, d, J = 10.5 Hz, Hb-6), 3.61 (2H, t, J = 6.2 Hz, H-l), 2.06 (2H, q, J = 7.1 Hz, H-4), 1.59-1.50 (2H, m, H-2), 1.47- 1.39 (2H, m, H-3), 0.89 (9H, s, SiC(CH3)3), 0.05 (6H, s, Si(CH3)2); 5c (100 MHz; CDCb) 139.0 (CH, C-5), 114.3 (CH2, C-6), 63.1 (CH2, C-l), 33.5 (CH2, C-4), 32.3 (CH2, C-2), 26.0 (3 x CH3, SiC(CH3)3), 25.2 (CH2, C-3), 18.4 (C, SiC(CH3)3), -5.3 (2 x CH3, (1255) Si(CH3)2) . Spectroscopic data were consistent with those reported in literature |
100% | With 1H-imidazole In dichloromethane at 20℃; for 19h; | |
100% | With 1H-imidazole In dichloromethane at 0 - 30℃; for 5h; Inert atmosphere; | 1. t-butyl-(hex-5-en-1-yloxy)dimethylsilane (9): To a 0 oC cooled solution of 5-hexen-1-ol 8 (4.2 g, 0.042 mol, 1 eq.) in dry DCM (45 ml) was added imidazole (3.43 g, 0.0504 mol, 1.2 eq) and TBS chloride (6.93 g, 0.0462 mol, 1.1 eq) at the same temperature under nitrogen atmosphere. Reaction mass was stirred for the 5 hours (the reaction progress was monitered by TLC) at 30 oC and then ice-cold water was added to quench the reaction mass. Then it was extracted with DCM, washed with brine solution, dried over MgSO4 and filtered. All organic layers were concentrated under reduced pressure followed by silica gel column chromatography (eluent 1% to 3% ethylacetate:hexane) afforded the title compound 9 in quantitative yield (7 g) as colourless oil. FT-IR (neat): 3074, 2943, 2865, 1630, 1105, 842, 778 cm-1; 1H NMR (500 MHz, CDCl3) δ 5.81 (ddt, J = 16.9, 10.2, 6.7 Hz, 1H), 5.03-4.97 (m, 1H), 4.96-4.92 (m, 1H). 3.61 (t, 2H, J = 10 Hz), 2.09-2.03 (m, 2H), 1.56-1.50 (m, 2H), 1.46-1.39 (m, 2H), 0.89 (s, 9H), 0.05 (s, 6H). 13C-NMR (125 MHz, CDCl3) δ 138.9, 114.3, 63.0, 33.5, 32.3, 25.9, 25.1, 18.3, -5.29; ESIMS (m/z) = 237 [M+Na]+. |
99% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 23℃; | |
99% | With 1H-imidazole; dmap In dichloromethane at 0 - 20℃; Inert atmosphere; | |
98% | With 1H-imidazole In dichloromethane at 20℃; Inert atmosphere; | |
97% | With dmap; triethylamine In dichloromethane | |
96% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; | |
93% | With 1H-imidazole In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere; | 4.1. Tert-butyl (hex-5-enyloxy) dimethylsilane (4) To a cooled (0 °C) solution of 5-hexen-1-ol 3 (5 g, 50 mmol) in dry CH2Cl2 (60 mL) was added imidazole (6.8 g, 100 mmol) and tert-butyl dimethyl silyl chloride (8.25 g, 55.0 mmol) under N2 atmosphere and stirred for 3 h at r.t. After completion of the reaction, the reaction mixture was diluted with H2O and extracted into CH2Cl2 (2 × 50 mL), dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by column chromatography (Hexane: EtOAc 9.5:0.5) to obtain pure compound 4 (9.9 g, 93%) as colorless liquid. IR (neat): 2932, 2859, 1254, 1102, 836, 773 cm-1. 1H-NMR (300 MHz, CDCl3): 5.89-5.74 (m, 1 H), 5.06-4.91 (m, 2 H), 3.61 (t, J = 6.2 Hz, 2 H), 2.11-2.01 (m, 2 H), 1.60-1.36 (m, 4 H), 0.89 (s, 9 H), 0.04 (s, 6 H). 13C-NMR (75 MHz, CDCl3): 138.8, 114.3, 63.0, 33.5, 32.3, 25.9, 25.2, 18.3,-5.3. ESI -MS: 429 [M+2]+ . |
92% | With 1H-imidazole In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; | |
90% | With 1H-imidazole In tetrahydrofuran at 0 - 20℃; for 16h; | |
90% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; | |
89% | With 1H-imidazole In N,N-dimethyl-formamide | |
88% | With 1H-imidazole In dichloromethane at 20℃; for 72h; | |
88% | With 1H-imidazole In dichloromethane at 20℃; for 6h; | |
87% | With 4-penten-1-yl cyclopropane In tetrahydrofuran at 20℃; | |
78% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 30h; | |
70% | Stage #1: 5-Hexen-1-ol With pyridine; triethylamine In acetonitrile at 20℃; for 0.0833333h; Stage #2: tert-butyldimethylsilyl chloride In acetonitrile at 20 - 60℃; for 1h; | |
70% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; | |
65% | With 1H-imidazole In N,N-dimethyl-formamide for 20h; Heating; | |
With 1H-imidazole In N,N-dimethyl-formamide | ||
Stage #1: 5-Hexen-1-ol With 1H-imidazole In N,N-dimethyl-formamide at 0℃; for 0.166667h; Stage #2: tert-butyldimethylsilyl chloride In N,N-dimethyl-formamide at 0 - 23℃; for 1.66667h; Further stages.; | ||
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 5h; | ||
With 1H-imidazole In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; | ||
With 1H-imidazole |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With pyridine at 0 - 5℃; for 3h; | |
100% | With triethylamine In dichloromethane at 0 - 20℃; for 12h; | 22.a a. hex-5-enyl 4-methylbenzenesulfonate (31): Example 22: Preparation of 5-(hex-5-enylamino)-2-hydroxy-3-(undec-10-enyl)cyclohexa-2,5- diene-l,4-dione (37): a. hex-5-enyl 4-methylbenzenesulfonate (31): To a solution containing 2.0 g (20 mmol) of 5-hexen-l-ol and 3.1 mL (2.2 g, 5.5 mmol) of triethylamine in 60 mL of anh dichloromethane was added 4.2 g (22 mmol) of p-toluenesulfonyl chloride at 0 °C. The reaction mixture was allowed to warm to room temperature and stirred for 12 h. The reaction mixture was then diluted with 100 mL of dichloromethane and washed with two 30-mL portions of 10% aq NaHC03 and brine. The organic layer was dried (MgS04) and then concentrated under diminished pressure to afford a crude residue. The residue was purified by flash column chromatography on a silica gel column (24 χ 3cm). Elution with 4:1 hexanes-ethyl acetate gave compound 31 as a colorless oil: yield 5.07 g (100%); silica gel TLC iff 0.65 (1 :1 ethyl acetate-hexanes); 1H NMR (CDC13) δ 1.41 (quin, 2H, J= 15.2 and 7.60 Hz), 1.60-1.71 (m, 2H), 1.97 (q, 2H, J= 14.4 and 7.20 Hz), 2.45 (s, 3H), 4.03 (t, 2H, J= 6.40 Hz), 4.89-4.95 (m, 2H), 5.65-5.78 (m, 1H), 7.34 (d, 2H, J= 8.40 Hz) and 7.79 (d, 2H, J= 8.40 Hz); 13C NMR (CDC13) δ 21.8, 24.7, 28.3, 33.0, 70.6, 115.2, 128.0, 129.9, 133.3, 138.0 and 144.8. |
100% | With dmap; triethylamine In dichloromethane at 20℃; | 41.1 Step 1: Hex-5-en-1-yl 4-methylbenzenesulfonate: To a 100 mL RBF was added hex-5-en-1-ol (2 g, 19.97 mmol), triethylamine (5.57 ml, 39.9 mmol) and 4- methylbenzenesulfonyl chloride (5.71 g, 30.0 mmol) in DCM (39.9 ml). The mixture was treated with DMAP (0.244 g, 1.997 mmol). The reaction was stirred at room temperature until the reaction was determined to be complete by KMn04 stain. The mixture was evaported to dryness, loaded onto a 40g silica column and purified by MPLC using a 0% to 10% ethyl acetate to hexanes gradient. Fractions containing the desired product were collected and concentrated in vacuo to yield the title compound (5.078 g, 100% yield). LCMS Tr = 0.99 m, MS ESI m/z = 255.2 (M+H) (Method 3). |
98% | With dmap; triethylamine In dichloromethane at 0 - 20℃; for 13h; Inert atmosphere; | |
98% | With dmap; triethylamine In dichloromethane at 0 - 20℃; for 13h; Cooling with ice; | |
98% | With dmap; triethylamine In dichloromethane at 20℃; for 1h; Inert atmosphere; | |
97% | With dmap; triethylamine In dichloromethane at 0 - 25℃; for 17h; | |
95% | With triethylamine In dichloromethane at 0 - 20℃; | |
95% | With pyridine In dichloromethane at 0℃; for 1h; Sonication; | |
93% | With pyridine In dichloromethane for 12h; Ambient temperature; | |
91% | With triethylamine In dichloromethane at 20℃; | |
90% | With dmap; triethylamine In dichloromethane at 20℃; | |
88% | With pyridine; potassium iodide at 0℃; for 4h; | |
85% | With pyridine In dichloromethane at 0℃; | |
83% | With potassium carbonate; 1-hexadecyl-1H-imidazole In water at 25℃; for 4h; | |
83% | With triethylamine In dichloromethane at 0 - 20℃; for 5h; | |
80% | With pyridine In dichloromethane at 0 - 20℃; for 24h; | |
76% | With pyridine | |
66.3% | With pyridine at 0℃; for 4h; | 4.2.3. Hex-5-en-1-yl 4-methylbenzenesulfonate A solution of 5-hexen-1-ol (12.51 g, 0.125 mmol) in distilled pyridine (20 mL, 0.248 mol) in a round bottom flask was cooled with an ice-bath and then p -toluenesulfonate chloride (21.65 g, 0.114 mol) was added. After stirring the mixture at 0 °C for 4 hours, iced water/concentrated HCl (45 mL, 4:1 v/v ) was added to the mixture. 90 mL diethyl ether was added and the organic upper phase was separated. The organic phase was dried over anhy- drous MgSO 4 . The mixture was filtered and the diethyl ether was removed by rotary evaporator. The product was purified by sil- ica column chromatography, using n-hexane/ethyl acetate (4:1, v/v ) eluent to obtain a colourless liquid (19.22 g, 75.6 mmol, 66.3%). 1 H NMR (600 MHz, δin TMS): 1.41 (tt, 2H, J = 9.6, 6.6 Hz, C H 2 CH 2 OTs), 1.65 (m, 2H, = CHCH 2 C H 2 ), 2.00 (qd, 2H, 7.3, 1.4 Hz, = CH C H 2 ), 2.45 (s, 3H, Me), 4.03 (t, 2H, J = 6.5 Hz, C H 2 OTs), 4.95 (m, 2H, CH = C H 2 ), 5.72 (ddt, 1H, J = 16.9, 10.1, 6.7 Hz, C H = CH2), 7.34 (d, 2H, J = 8.1 Hz, 3,3’-Ar), 7.79 (d, 2H, J = 8.2 Hz, 2,2’-Ar); 13 C{ 1 H} NMR (151 MHz, δin NMR): 21.6 (s, Me), 24.8 (s, = CHCH 2 C H 2 ), 28.2 (s, C H 2 CH 2 OTs), 32.9 (s, = CH C H 2 ), 70.4 (s, C H 2 OTs), 115.1 (s, CH = C H 2 ), 127.9 (s, 2,2’-Ar), 129.8 (s, 3,3’-Ar), 133.3 (s, 4- Ar), 137.9 (s, C H = CH 2 ), 144.7 (s, 1-Ar). |
66% | With dmap; triethylamine In dichloromethane at 0 - 20℃; | |
64% | With pyridine In dichloromethane at 0 - 26℃; for 1h; Inert atmosphere; | |
60% | With dmap; triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; | |
55% | With potassium hydroxide In dichloromethane at 20℃; for 24h; Inert atmosphere; | Intermediate 117a: Hex-5-en-1-yl 4-methylbenzenesulfonate Intermediate 117a: Hex-5-en-1-yl 4-methylbenzenesulfonate p-Toluenesulfonyl chloride (1.6 g, 8.4 mmol) was added to powdered potassium hydroxide (1.6 g, 24 mmol) and 5-hexen-1-ol (1.0 mL, 8.3 mmol) in DCM at 20° C. over a period of nitrogen. The resulting suspension was stirred at 20° C. for 1 day. The reaction mixture was filtered through celite, rinsing with DCM (100 mL). The filtrate was evaporated to dryness to afford a colourless oil. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in heptane to afford the title compound (1.16 g, 55%) as a colourless oil. 1H NMR (400 MHz, CDCl3, 30° C.) 1.44 (2H, p), 1.64-1.73 (2H, m), 2.03 (2H, q), 2.47 (3H, s), 4.06 (2H, t), 4.92-5.05 (2H, m), 5.74 (1H, ddt), 7.37 (2H, d), 7.81 (2H, d). |
51% | With pyridine | |
51% | With pyridine for 72h; Cooling; | |
20.2 g | With pyridine at 0℃; for 4h; | |
With pyridine | ||
With pyridine | ||
With pyridine at 0℃; for 3.5h; | ||
With dmap; triethylamine In dichloromethane at 0 - 20℃; | ||
With pyridine at 0℃; for 3h; | To a solution of TsCl (6.46 g, 34 mmol) in pyridine (26 mL) was addedhex-5-en-1-ol (2.4 mL, 20 mmol) at 0 °C and the resulting mixture was stirred at that temperaturefor 3 h. The resulting mixture was quenched by addition of 1N HCl. The organic layer wasseparated, and the aqueous layer was extracted with Et2O (30 mL x 4). The combined organiclayer was washed with 1N HCl and brine, dried over Na2SO4 and concentrated under reduced pressure to afford a crude material (4.98 g). To a suspension of LiCl (1.66 g, 39 mmol) in acetone(5 mL) was added a solution of the crude material in acetone (35 mL). The resulting mixture wasstirred at 50 °C for 3 h. Another portion of LiCl (1.66 g, 39 mmol) was added, and stirring wascontinued for another 30 min at 75 °C. After cooling to room temperature, the reaction mixturewas filtered through a pad of Celite and concentrated under reduced pressure. Silica gelchromatography afforded the title compound as a colorless oil (242 mg, 10%). The 1H NMRspectra of the compound showed good agreement with the literature data.13 | |
With triethylamine In dichloromethane at 20℃; Inert atmosphere; Schlenk technique; | ||
With dmap; triethylamine In dichloromethane at 0 - 20℃; | ||
With triethylamine In dichloromethane at 0 - 20℃; for 10h; | ||
With triethylamine In dichloromethane at 0 - 20℃; for 5h; Inert atmosphere; | ||
With pyridine; dmap In dichloromethane at 0 - 20℃; for 25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With 2,6-dimethylpyridine; 4-methoxy-benzaldehyde In acetonitrile at 25℃; for 23h; Schlenk technique; Inert atmosphere; Sealed tube; Irradiation; | |
93% | With triethyl borane for 1.5h; | |
91% | With 2,2'-azobis(isobutyronitrile) at 80℃; |
91% | With 2,2'-azobis(isobutyronitrile) at 65℃; for 12h; Inert atmosphere; Sealed tube; | 45.1 Step-1: 7,7, 8, 8, 9, 9, 10, 10, 11, 11, 12, 12, 12-Tridecafluoro-5-iodododecan-1-ol A mixture of 1,1.1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-6-iodohexane (50 g, 112 mol), hex- 5- en-1-ol (1 23 g, 112 mmol) and AIBN (1.841 g, 11.21 mmol) was heated at 85 °C in a sealed glass tube filled with nitrogen gas for 12 h while gentle stirring. TLC showed presence of new compound. The crude reaction mixture was purified by silica gel chromatography to afford 7, 7, 8, 8, 9, 9, 10, 10, 11, 11, 12, 12, 12-tridecafluoro-5-iodododecan-1- ol (56 g, 103 mmol, 91 % yleld). 1H NMR (400 MHz, CDC): d 4.37-4.33 (m, 1 H), 366- 3.41 (m, 2H), 3.41 (br, 1H), 2.96-2.78 (m, 2H), 1.89-1.83 (, 2H), 1.67-1.50 (, 4H) |
91% | With 2,2'-azobis(isobutyronitrile) at 65℃; for 12h; Inert atmosphere; Sealed tube; | 45.1 Step-1: 7,7, 8, 8, 9, 9, 10, 10, 11, 11, 12, 12, 12-Tridecafluoro-5-iodododecan-1-ol A mixture of 1,1.1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-6-iodohexane (50 g, 112 mol), hex- 5- en-1-ol (1 23 g, 112 mmol) and AIBN (1.841 g, 11.21 mmol) was heated at 85 °C in a sealed glass tube filled with nitrogen gas for 12 h while gentle stirring. TLC showed presence of new compound. The crude reaction mixture was purified by silica gel chromatography to afford 7, 7, 8, 8, 9, 9, 10, 10, 11, 11, 12, 12, 12-tridecafluoro-5-iodododecan-1- ol (56 g, 103 mmol, 91 % yleld). 1H NMR (400 MHz, CDC): d 4.37-4.33 (m, 1 H), 366- 3.41 (m, 2H), 3.41 (br, 1H), 2.96-2.78 (m, 2H), 1.89-1.83 (, 2H), 1.67-1.50 (, 4H) |
89% | With 2,6-dimethylpyridine In acetonitrile at 20℃; for 12h; Irradiation; Inert atmosphere; Sealed tube; | |
87% | With o-phenylenebis(diphenylphosphine); cobalt(II) bromide; zinc In water; acetone at 20℃; for 3h; Inert atmosphere; stereoselective reaction; | |
81% | With C30H26N6Ru(2+)*2Cl(1-); sodium L-ascorbate In methanol; acetonitrile for 0.5h; Inert atmosphere; Irradiation; | |
80% | With potassium carbonate In N,N-dimethyl-formamide for 24h; Schlenk technique; Inert atmosphere; Irradiation; | |
80% | With pyrrolidine; Diphenylacetaldehyde In dichloromethane at 20℃; for 16h; Inert atmosphere; Irradiation; | |
54% | With 2',4',5',7'-tetrabromofluorescein; sodium thiosulfate In water; acetonitrile at 20℃; for 1h; Inert atmosphere; Irradiation; | |
35% | With 2,6-diiodo-4,4-difluoro-1,3,5,7-tetramethyl-8-phenyl-4-bora-3a,4a-diaza-s-indacene; sodium L-ascorbate; lithium bromide In water; N,N-dimethyl-formamide at 20℃; for 20h; Inert atmosphere; Schlenk technique; Irradiation; | |
35% | With 7-(diethylamino)-3-(thiophen-2-yl)-2H-chromen-2-one In ethanol; water at 20℃; for 36h; Schlenk technique; Inert atmosphere; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With titanium silicate; dihydrogen peroxide In acetone at 59.9℃; | |
70% | With dihydrogen peroxide In water at 60℃; for 6h; | |
54% | With (CF3CO2)ReO3; trifluoroacetic anhydride In dichloromethane at 20℃; |
90 % Chromat. | With molecular sieve; dihydrogen peroxide In acetone at 59.85℃; for 6h; | |
Multi-step reaction with 2 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0 - 20 °C 2: 1,1-dibromomethane; hexabromobenzene / 140 h / 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 1H-imidazole In dichloromethane at 0 - 20℃; for 5h; | |
99% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; | |
99% | With 1H-imidazole In dichloromethane at 23℃; for 2h; |
98% | Stage #1: 5-Hexen-1-ol With 1H-imidazole In dichloromethane at 0℃; for 0.166667h; Stage #2: tert-butylchlorodiphenylsilane In dichloromethane at 0 - 20℃; for 17h; | |
97% | With tetra-(n-butyl)ammonium iodide; sodium hydride In tetrahydrofuran at 0℃; Inert atmosphere; | |
97% | Stage #1: 5-Hexen-1-ol With sodium hydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #2: tert-butylchlorodiphenylsilane With tetra-(n-butyl)ammonium iodide In tetrahydrofuran Inert atmosphere; | |
94% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 0.666667h; | |
85% | With sodium hydride In N,N-dimethyl-formamide at 20℃; for 5h; Inert atmosphere; | |
81% | With 1H-imidazole In tetrahydrofuran at 0℃; for 16h; Inert atmosphere; | |
4.05 g | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 2h; | |
With 1H-imidazole In dichloromethane at 0 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | |
92% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | |
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran; toluene at 20℃; for 3h; |
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 24h; Inert atmosphere; | 4.3 Preparation of various alkenes starting material. Synthesis of hex-5-en-1-yl benzoate (3a) To a flame-dried 250mL two-neck flask containing a magnetic stirring bar were added 51 4-dimethylaminopyridine (DMAP, 488mg, 4mmol), 52 N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDCI, 7.67g, 40mmol), 53 benzoic acid (2.74g, 24mmol) and 54 5-hexen-1-ol (2.00g, 20mmol) in 100mL 55 CH2Cl2 under N2 atmosphere at 0 . The reaction mixture was stirred at room temperature for 24h. After that, the organic phase was filtered through a pad of celite and concentrated. The resulting residue was purified by silica gel column chromatography (EA/PE=1:20 v/v) to give a colorless 56 liquid. (4.08g, yield 87%) hex-5-en-1-yl benzoate (3a) [27]: Obtained as colorless liquid in 87% yield by silica gel flash column chromatography eluted with EA/PE=1:20 v/v. 1H NMR (400MHz, CDCl3) δ 8.07 - 8.02 (m, 2H), 7.59 - 7.52 (m, 1H), 7.44 (dd, J=10.6, 4.7Hz, 2H), 5.82 (ddt, J=16.9, 10.2, 6.7Hz, 1H), 5.08 - 4.95 (m, 2H), 4.33 (t, J=6.6Hz, 2H), 2.18 - 2.10 (m, 2H), 1.83 - 1.75 (m, 2H), 1.61 - 1.51 (m, 2H). 13C NMR (100MHz, CDCl3) δ 166.5, 138.3, 132.8, 130.4, 129.5, 128.3, 114.8, 64.8, 33.3, 28.1, 25.3. GC-MS (EI): m/z=204.0 (M+). |
With toluene-4-sulfonic acid In toluene Heating; | ||
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With tris(para-trifluoromethyl)phenyl phosphine In 1,1,2,2-tetrachloroethane at 70℃; | |
88% | With ytterbium(III) triflate at 120℃; Inert atmosphere; Ionic liquid; | |
88% | With 1-ethyl-3-methylimidazolium triflate; ytterbium(III) triflate at 120℃; Inert atmosphere; regioselective reaction; |
62% | With 3-butyl-1-(butyl-4-sulfobutyl)imidazolium trifluoromethanesulfonate In benzene at 80℃; for 71h; Inert atmosphere; | |
85 %Chromat. | With [Nd(acetonitrile)9][AlCl4]3*acetonitrile In 1,2-dichloro-ethane at 83℃; for 24h; Inert atmosphere; Schlenk technique; regioselective reaction; | 4.3. Typical procedure for hydroalkoxylation of unactivated alkenols (product 2b as an example) General procedure: Into a 10 mL of Schlenk tube under dried argon were added II (0.0265 g, 0.025 mmol), DCE (2.0 mL) and 4-pentenol (0.10 mL, 1.0 mmol). The resulting mixture was stirred at 83 °C for 24 h. The reaction was cooled to room temperature and the catalyst was removed by filtration through a short pad of silica gel. Product 2b was obtained by silica-gel column chromatography with pentane/diethyl ether or petroleum ether/ethyl acetate as an eluent. The GC yield of 90% was determined with nonane as internal standard. |
74 %Spectr. | With 1,1,2,2-tetramethyl-1,2-ethanediamino-N,N'-bis(3,5-di-tert-butylsalicylidene)-cobalt(II); 2-Iodobenzoic acid; phenylsilane; 1-fluoro-2,4,6-trimethylpyridin-1-ium tetrafluoroborate In d(4)-methanol at 20℃; for 18h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: 5-Hexen-1-ol With triethylamine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: 4,4'-dimethoxytrityl chloride In dichloromethane at 0 - 20℃; for 4h; Inert atmosphere; | 26; 48 5-Hexenol (6.OmL, 50.5 mmol) was dissolved in dichloromethane (120 mL). To this solution triethylamine (14 mL, 151.5 mmol) was added. The reaction mixture stined under argon for 30 minutes at 0°C. Then DMTr-Cl (18 g, 53.0 mmol) was added to the solution at 0 °C. The mixture stirred under vacuum followed by argon, and stirring was continued under argon at room temperature for 4 hours. The reaction mixture was washed with water twice followed by saturated sodium chloride. The organic layer was dried over sodium sulfate, filtered and evaporated to dryness to afford compound 127 (Rf = 0.85 in 25% EtOAc in Hexane) (18.9 g, 95%) as a yellow oil. ‘H NMR (400 MHz, DMSO-d6): ö 7.42 - 7.03 (m, 7H), 7.01 - 6.74 (m, 6H), 5.85-5.63 (m, 1H), 5.05-4.77 (m, 2H), 3.93-3.47 (m, 6H), 2.93 (dd, J= 21.1, 14.7 Hz, 2H), 2.49 (dd, J= 3.5, 1.7 Hz, 2H), 1.66- 1.47 (m, 4H). |
With pyridine at 0℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 2h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: 5-Hexen-1-ol; 1-Phenyl-1H-tetrazole-5-thiol With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 3h; Stage #2: With ammonium molybdate; dihydrogen peroxide In tetrahydrofuran; ethanol at 20℃; | |
78% | Stage #1: 5-Hexen-1-ol; 1-Phenyl-1H-tetrazole-5-thiol With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 3h; Stage #2: With dihydrogen peroxide In water at 20℃; | 5-(Hex-5-en-1-ylsulfonyl)-1-phenyl-1H-tetrazole: To a solution of 5-hexen-1-ol (85) (135 μL, 1.18 mmol, 1.00 eq), phenyltetrazole thiol (240 mg, 1.35 mmol, 1.15 eq) andPPh3 (353 mg, 1.35 mmol, 1.15 eq) in THF (6 mL) was added DEAD (212 μL, 1.35 mmol,1.15 eq) dropwise at rt. The orange colour of the drops discharged upon contact with themixture until the very last drops and a slight warming was observed. The resulting paleyellow solution was stirred for 3 h. Then EtOH (10 mL) was added and the reaction wascooled to 0 °C. Afterwards a previously prepared solution of ammonium molybdatetetrahydrate (229 mg, 0.185 mmol, 16 mol%) in aqueous H2O2 (30%, 1.86 mL) was addedvia pipette. The cooling was removed after a few minutes and the mixture was stirred atrt overnight. Then it was diluted with water (40 mL) and dichloromethane. The layerswere separated and the aqueous phase was extracted with CH2Cl2 (3×20 mL). Thecombined organic extracts were washed with brine and concentrated under reducedpressure. The dark orange crude was purified by column chromatography (hex:EtOAc5:1) to afford the title compound 86 (269 mg, 78%) as a pale yellow oil.TLC (hex:EtOAc 5:1): Rf = 0.301H-NMR (CDCl3, 400.1 MHz): δ = 7.72-7.67 (m, 2H), 7.65-7.57 (m, 3H), 5.77 (tdd, J = 6.7 Hz,J = 10.2 Hz, J = 16.9 Hz, 1H), 5.09-4.96 (m, 2H), 3.75 (mc, 2H), 2.13 (mc, 2H), 1.98 (mc, 2H),1.61 (mc, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | In toluene; xylene at 20℃; | |
With platinum-containing catalyst |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 440 °C / Leiten ueber Glaswolle 2: ethanolic KOH-solution |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine In dichloromethane at 0 - 20℃; for 21h; | 8.1 Synthesis of hex-5-enyl 4-nitrobenzoate Example 8 Synthesis of (5S,6R)-5,6-bis(nitrooxy)heptyl 3-methyl-3-(2,4,5-trimethyl-3,6- dioxocyclohexa-l,4-dienyl)butanoate ((5S,6R)-isomer of Compound 8) Step 1 : Synthesis of hex-5-enyl 4-nitrobenzoate At 0°C, a solution of 5-hexen-l-ol (19.4 mL; 161.54 mmol) in dichloromethane (513 mL), was added with p-nitrobenzoyl chloride (35.97 g, 193.85 mmol) followed by a solution of triethylamine (27.0 mL, 193.85 mmol) in dichloromethane (150 mL) dropwise. The mixture was stirred at ambient temperature for 21 hours, then washed with water, 1M aqueous HCl, brine. The organic layer was dried (Na2S04) and the solvent removed under reduced pressure. The residue was purified by flash chromatography (Biotage System, two SNAP Cartridge silica 340 g, eluent: n-hexane/ethyl acetate 90/10 to n-hexane/ethyl acetate 50/50 during 12 CV) to give the title compound as a yellow oil (40.00 g, 99%). 1H NMR (300 MHz, CDC13) δ 8.30 (dt, J = 9.0, 3.0 Hz, 2H), 8.22 (dt, J = 9.0, 3.0 Hz, 2H), 5.83 (1H, ddt, J = 16.9, 10.2, 6.7 Hz), 4.95-5.11 (2H, m), 4.39 (2H, t, J = 6.6 Hz), 2.15 (2H, m), 1.84 (2H, m)1.50-1.66 (2H, m). |
99% | With triethylamine In dichloromethane at 0 - 20℃; for 21h; | 8.1 Step 1 : Synthesis of hex-5-enyl 4-nitrobenzoate Example 8 Synthesis of (5S,6R)-5,6-bis(nitrooxy)heptyl 3-methyl-3-(2,4,5-trimethyl-3,6- dioxocyclohexa-l, Step 1 : Synthesis of hex-5-enyl 4-nitrobenzoate At 0°C, a solution of 5-hexen-l-ol (19.4 mL; 161.54 mmol) in dichloromethane (513 mL), was added with p-nitrobenzoyl chloride (35.97 g, 193.85 mmol) followed by a solution of triethylamine (27.0 mL, 193.85 mmol) in dichloromethane (150 mL) dropwise. The mixture was stirred at ambient temperature for 21 hours, then washed with water, 1M aqueous HCl, brine. The organic layer was dried (Na2S04) and the solvent removed under reduced pressure. The residue was purified by flash chromatography (Biotage System, two SNAP Cartridge silica 340 g, eluent: n-hexane/ethyl acetate 90/10 to n-hexane/ethyl acetate 50/50 during 12 CV) to give the title compound as a yellow oil (40.00 g, 99%). 1H NMR (300 MHz, CDC13) δ 8.30 (dt, J = 9.0, 3.0 Hz, 2H), 8.22 (dt, J = 9.0, 3.0 Hz, 2H), 5.83 (1H, ddt, J = 16.9, 10.2, 6.7 Hz), 4.95-5.11 (2H, m), 4.39 (2H, t, J = 6.6 Hz), 2.15 (2H, m), 1.84 (2H, m)1.50-1.66 (2H, m). |
99% | With triethylamine In dichloromethane at 0 - 20℃; for 21h; | 7.1 Synthesis of hex-5-enyl 4-nitrobenzoate At 0°C, a solution of 5-hexen-l-ol (19.4 mL; 161.54 mmol) in dichloromethane (513 mL), was added with p-nitrobenzoyl chloride (35.97 g, 193.85 mmol) followed by a solution of triethylamine (27.0 mL, 193.85 mmol) in dichloromethane (150 mL) dropwise. The mixture was stirred at ambient temperature for 21 hours, then washed with water, 1M aqueous HCl, brine. The organic layer was dried (Na2S04) and the solvent removed under reduced pressure. The residue was purified by flash chromatography (Biotage System, two SNAP Cartridge silica 340 g, eluent: n-hexane/ethyl acetate 90/10 to n-hexane/ethyl acetate 50/50 during 12 CV) to give the title compound as a yellow oil (40.00 g, 99%). 1H NMR (300 MHz, CDC13) δ 8.30 (dt, J = 9.0, 3.0 Hz, 2H), 8.22 (dt, J = 9.0, 3.0 Hz, 2H), 5.83 (1H, ddt, J = 16.9, 10.2, 6.7 Hz), 4.95-5.11 (2H, m), 4.39 (2H, t, J = 6.6 Hz), 2.15 (2H, m), 1.84 (2H, m) 1.50-1.66 (2H, m). |
96% | With triethylamine In dichloromethane at 0 - 20℃; for 4h; | 1.1 Step 1Hex-5-enyl 4-nitrobenzoateTriethylamine (9.1 mL, 66 mmole, 1 eq) was added to a stirred solution of hex-5-enol (6.6 g, 66 mmole) and 4-nitrobenzoyl chloride (12.3 g, 66 mmole, 1 eq.) in dichloromethane (100 mL) at 00C. The reaction was stirred at room temperature for 4 h and extracted with water, HCl IM, water and brine. The solvent was removed under reduced pressure to give a crude oil which was treated with n-hexane to give a solid that was filtered off. The mother liquor was evaporated to give hex-5-enyl 4- nitrobenzoate as yellow oil (15.8 g, 96%). |
82% | With triethylamine In dichloromethane at 20℃; for 4h; | 7.1 Step 1 : Synthesis of Hex-5-enyl-4-nitrobenzoate To a stirred solution of hex-5-enol (21.25 g, 200 mmol) and 4-nitrobenzoyl chloride (37.11 g, 200 mmol) in dichloromethane (300 mL) at 0°C, triethylamine (28 mL, 200 mmol) was added. The reaction was stirred at RT for 4 h and washed with water, HCl 1M, water and brine. The solvent was removed under reduced pressure to give a crude oil which was treated with n-hexane to give a solid that was filtered off. The mother liquor was evaporated to give the title compound as yellow oil (41 g, 82 %). MS: m/z = 250 [M+H]+ TLC: DCM 100 % Rf = 0.4 |
82% | With triethylamine In dichloromethane at 0 - 20℃; for 4h; | 2.1 Step 1: Synthesis of Hex-5-enyl-4-nitrobenzoate To a stirred solution of hex-5-enol (21.25 g, 200 mmol) and 4-nitrobenzoyl chloride (37.11 g, 200 mmol) in DCM (300 mL) at 0° C., triethylamine (28 mL, 200 mmol) was added. The reaction was stirred at room temperature for 4 h and washed with water, HCl 1M, water and brine. The solvent was removed under reduced pressure to give a crude oil which was treated with n-hexane to give a solid that was filtered off. The mother liquor was evaporated to give the title compound as yellow oil (41 g, 82%). MS: m/z=250 [M+H]+TLC: DCM 100% Rf=0.4 |
82% | With triethylamine In dichloromethane at 0 - 20℃; for 4h; | 1.1 Step 1: Synthesis of Hex-5-enyl-4-nitrobenzoate To a stirred solution of hex-5-enol (21.25 g, 200 mmol) and 4-nitrobenzoyl chloride(37.11 g, 200 mmol) in dichloromethane (300 mL) at 0°C, triethylamine (28 mL, 200 mmol) was added. The reaction was stirred at RT for 4 h and then washed with water, HC1 1M, water and brine. The solvent was removed under reduced pressure to give a crude oil which was treated with n-hexane to give a solid that was filtered off. The mother liquor was evaporated to give the title compound as yellow oil (41 g, 82%).MS: m/z = 250 [M+H]+TLC: DCM 100% Rf = 0.4 |
70% | With dmap; dmap; triethylamine In dichloromethane at 0 - 20℃; for 2h; | 4.1. To a solution of hex-5-en-1-ol (20.0 g, 200 mmol) in CH2C12 (350 mL, 0.57 M) at 0 DEG C was added triethylamine (33.7 mL, 240 mmol, 1.2 equiv), DMAP (1.22 g, 10 mmol, 0.05 equiv) and then 4-nitrobenzoyl chloride (39 g, 210 mmol, 1.05 equiv. ). The reaction was stirred at rt for 2 h. The reaction mixture was quenched with a saturated NH4C1 solution and extracted 3 times with CH2C12. The combined organic layers were washed with brine, dried over Na2S04, filtered and evaporated. The product was purified by combi-flash 2x120 g silica gel cartridge using gradient (0-5 % in 5 min, 5-25 % in 30 min, 25-40 % EA/Hex in 10 min) to afford the desired product (35 g, Yield = 70 %) as a yellowish oil. 1H NMR (500 MHz, Acetone): δ 8.36 (d, 2 H), 8.26 (d, 2 H), 5.87-5. 79 (m, 1H), 5.03 (d, 1 H), 4.94 (d, 1 H), 4.38 (t, 2 H), 2.14 (m, 2 H), 1. 84-1. 78 (m, 2 H), 1.60-1. 54 (m, 2 H). |
70% | With dmap; triethylamine In dichloromethane at 0 - 20℃; for 2h; | 2.1 EXAMPLE 2 (5R)-5, 6-bis (nitrooxy) hexyl (2Z)-4- (acetyloxy)-3- [4- (methylsulfonyl) phenyl] -2-phenylbut-2- enoate Step 1: hex-5-en-1-yl 4-nitrobenzoate To a solution of hex-5-en-1-ol (20.0 g, 200 mmol) in CHzCI2 (350 mL, 0.57 M) at 0 C was added triethylamine (33.7 mL, 240 mmol, 1.2 equiv), DMAP (1.22 g, 10 mmol, 0.05 equiv) and then 4-Nitrobenzoyl chloride (39 g, 210 mmol, 1.05 equiv. ). The reaction was stirred at rt for 2 h. The reaction mixture was quenched with a saturated NH4Cl solution and extracted 3 times with CH2C12. The combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated. The product was purified by combi-flash 2x120 g silica gel cartridge using gradient (0-5 % in 5 min, 5-25 % in 30 min, 25-40 % EA/Hex in 10 min) to afford the desired product (35 g, Yield = 70 %) as a yellowish oil. 1H NMR (500 MHz, acetone-d6): 8 8.36 (d, 2H), 8. 26 (d, 2H), 5.87-5. 79 (m, 1H), 5.03 (d, 1H), 4.94 (d, 1H), 4. 38 (t, 2H), 2.14 (m, 2H), 1. 84-1. 78 (m, 2H), 1.60-1. 54 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.5 g (13%) | With potassium carbonate; In dichloromethane; triethylamine; N,N-dimethyl-formamide; | EXAMPLE 3 A mixture of 5-hexen-1-ol (5 g) and 8-azaspiro[4.5]decane-7,9-dione (14 ml) in triethylamine (150 ml) was cooled on an ice bath. Methane-sulfonyl chloride (8.6 g) in triethylamine (50 ml) was added dropwise and the mixture was stirred at room temperature for 1 hour. The mixture was filtered off and the filtrate evaporated. Dichloromethane (7.7 g), potassium carbonate (7.6 g) and N,N-dimethylformamide (100 ml) were added to the residue and the mixture was stirred at 160 C. overnight. The mixture was filtered off and the filtrate evaporated. The residue was purified by short open column chromatography over silica gel (eluent: CH2 Cl2 /CH3 OH 100/0 to 98/2). The pure fractions were collected and evaporated, yielding 1.5 g (13%) of 8-(5-hexenyl)-8-azaspiro[4.5]decane-7,9-dione (interm. 8). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With triethylamine; In dichloromethane; at 20℃; | Synthesis of O-rhex-S-envD-O-fsuccinimidvDcarbonate (8); A mixture of hex-5-enol (5.00 g, 49.9 mmol), disuccinimidyl carbonate (13.08 g, 51.1 mmol) and triethylamine (6.50 g, 64.2 mmol) in CH2CI2 (50 mL) was stirred at RT overnight. After completion, the reaction mixture was poured on ice, the organic layer was washed with water, dried (Na2SO4), filtered and evaporated to afford 10.25 g (85%) of 8 as a colourless oil. m/z = 242 (M+H)+; 1H NMR (CDCl3): 5.82-5.73 (m, IH), 5.07-4.96 (m, 2H), 4.33 (t, J= 6.3 Hz, 6.6 Hz, 2H), 2.85 (s, 4H), 2.15-2.06 (m, 2H), 1.82-1.72 (m, 2H), 1.56-1.47 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate; 1-n-butyl-3-methylimidazolim bromide; triethylamine; p-toluenesulfonyl chloride at 80℃; for 6h; Green chemistry; regioselective reaction; | General procedure for the one-pot N-alkylationof nucleobases via alcohols in ionic liquids General procedure: In a double-necked round-bottom flask (100 mL) wasadded a mixture consisting of nucleobase (0.01 mol),alcohol (0.012 mol), TsCl (2.86 g, 0.015), TEA (1.01 g,0.01 mol) and K2CO3 (1.38 g, 0.010 mol) in bmim[Br](10 mL). The flask was immersed in an oil bath, kept at80 °C and stirred for the time when TLC indicated no furtherprogress in the conversion (Tables 4, 5, 6). The mixturewas then diluted with water (200 mL) and extracted withEtOAc (3 × 50 mL). The organic layer was dried (Na2SO4)and evaporated to afford the crude product which was purifiedby traditional column chromatography on silica geleluting with proper solvents. |
83% | With potassium carbonate; triethylamine In N,N-dimethyl-formamide for 5h; Heating; | |
82% | With tetrachloromethane; tetra-(n-butyl)ammonium iodide; potassium carbonate; triphenylphosphine In N,N-dimethyl-formamide for 6h; Reflux; |
78% | With iodine; potassium carbonate; triethylamine; triphenylphosphine In N,N-dimethyl-formamide for 15h; Reflux; | General procedure for one-pot N-alkylation of nucleobases via alcohols using TPP/I2 General procedure: In a double-necked round bottom flask (100 mL) equipped with a condenser was added a mixture, consisting of alcohol (1 mmol),TPP (1 mmol), I2 (1 mmol) Et3N (1 mmol), K2CO3 (1 mmol), and thedesire nucleo base (1 mmol) in anhydrous DMF (5 mL).33 The mixture was heated at reflux. Heating was continued until TLC indicated no further improvement in the conversion (Table 5). The solvent was evaporated under vacuum and the remaining foam was dissolved in CHCl3 (100 mL) and subsequently washed with water (2100 mL). The organic layer was dried (Na2SO4) and evaporated. The crude product was purified by short column chromatography on silica gel eluting with proper solvents. |
75% | Stage #1: 5-Hexen-1-ol With phosphorus pentoxide; potassium iodide In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: adenine With potassium carbonate; triethylamine In N,N-dimethyl-formamide for 9h; Reflux; regioselective reaction; | 4.2 General procedure for synthesis of N-alkyl nucleobases via alcohols using P2O5/KI General procedure: To a double-necked round bottom flask (100mL), equipped with a condenser, it was added a mixture of KI (1.5mmol), P2O5 (1.5mmol) and the desired alcohol (1mmol) in DMF (5mL). The reaction mixture was stirred at r.t. for 30min. Next, the considered nucleobase (1mmol), K2CO3 (1mmol) and Et3N (1mmol) were added and the reaction mixture was heated to reflux for a further 6.5-10.5h (until TLC indicated no further progress in reaction, Table5). The solvent was then evaporated at reduced pressure, and the remaining foam was dissolved in chloroform (150mL) and washed with water (2×150mL). The organic layer was dried on Na2SO4 (1g) and evaporated. The product was purified using short column chromatography on silica gel eluting with proper solvents. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 20℃; for 1h; | N-Allyl-N-(hex-5-enyl)-2-nitrobenzenesulfonamide (8d) DEAD (6.5 mL, 15 mmol) was added to a stirred solution of 5-hexen-1-ol (1.2 mL, 10 mmol), N-allyl-2-nitrobenzenesulfonamide (2.42 g, 10 mmol) and triphenylphosphine (3.93 g, 15 mmol) in THF (30mL) at 0 C. The reaction mixture was warmed to room temperature and was stirred for 1 h.Concentration followed by column chromatography (hexane/AcOEt 4/1) gave 8d as a colorless oil(3.45 g, quant). |
98% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Example 4 Preparation of 5-hexenyl 5-aminolevulinate hydro chloride To 1 ml of thionyl chloride (SOCl2) were added 3 drops of N,N-dimethylformamide (DMF) with stirring. Following the addition of <strong>[5451-09-2]5-aminolevulinic acid hydrochloride</strong> (ALA.HCl, 200 mg, 1.19 mmol), the solution was stirred for 12 hours at room temperature. Concentration in a vacuum was conducted before the addition of 5-hexenol. Then, the reaction mixture was stirred for 1.5 hours at room temperature, followed by purification by silica gel chromatography to afford 5-hexenyl 5-aminolevulinate hydrochloride at a yield of 89%. 1H NMR (300 MHz, DMSO-d6): delta8.33 (s, 3H), 5.85~5.71 (m, 1H), 5.04~4.92 (m, 2H), 3.99 (t, J=6.5 Hz, 2H), 3.93 (s, 2H), 2.78 (t, J=6.6 Hz, 2H), 2.53 (t, J=6.6 Hz, 2H), 2.02 (q, J=7 Hz, 2H), 1.56 (quintet, J=6.7 Hz, 2H), 1.38 (quintet, J=5.1 Hz, 2H); 13C NMR (75 MHz, DMSO-d6): delta 202.66, 172.05, 138.41, 115.02, 63.92, 46.52, 34.26, 32.69, 27.56, 27.08, 24.55. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With triethanolamine; 4,5-dichloro-1-phenylpyridazin-6-one; sodium tris(acetoxy)borohydride; | Step 5: methyl N-hex-5-en-1-yl-3-methyl-L-valinate 99 Hex-5-enal 98 (obtained from hex-5-en-1-ol via a PCC oxidation) (0.95 eq.) was added at RT to a 0.11 M solution of (2S)-1-methoxy-3,3-dimethyl-1-oxobutan-2-aminium chloride (1.0 eq.) and TEA (1.0 eq.) in DCE. Sodium triacetoxyborohydride (1.0 eq.) was added in one portion and the reaction mixture was stirred at RT overnight. The reaction mixture was diluted with DCM/saturated aqueous NaHCO3. The phases were separated; the organic layer was washed with brine, dried (Na2SO4) and filtered though a short path of silica gel (PE:EtOAc=9:1) to afford the title compound 99 as a pale yellow liquid (72%). 1H NMR (300 MHz, CDCl3, 300 K) delta 5.89-5.71 (m, 1H), 5.07-4.88 (m, 2H), 3.71 (s, 3H), 2.88 (s, 1H), 2.62-2.48 (m, 1H), 2.45-2.31 (m, 1H), 2.13-1.98 (m, 2H), 1.67-1.54 (m, 1H), 1.53-1.35 (m, 4H), 0.95 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 23℃; | |
96% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 23℃; for 3.5h; | 1 To a stirred solution of 3-methoxy phenol (1.24 g, 10 mmol), 5-hexen-l-ol, 4a (1.4 mL, 12 mmol) and Ph3P (3.14g, 12 mmol) in THF (20 mL) at 0 0C was added diisopropylazodicarboxylate (2.3 mL, 12 mmol) dropwise. After stirring the solution for 30 min at 0 0C the reaction mixture was warmed to 23 0C and stirred for 3 h. The reaction mixture was concentrated in vacuo and the residue was subjected to column chromatography (98:2 hexanes:EtOAc) to yield 1.98 g of 5a (96% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 1.58-1.66 (m, 2H), 1.80-1.88 (m, 2H), 2.15-2.20 (m, 2H), 3.82 (s, 3H), 3.98 (t, J = 6.4 Hz, 2H), 5.02-5.12 (m, 2H), 5.83-5.92 (m, IH), 6.52-6.56 (m, 3H), 7.19-7.24 (m, IH); 13C NMR (100 MHz, CDCl3): δ 25.3, 28.7, 33.4, 55.1, 67.6, 100.9, 106.0, 106.6, 114.7, 129.8, 138.5, 160.3, 160.8; FT-IR (film, NaCl) vmax = 3075, 2939, 1599, 1493, 1287, 1200, 1152, 1046 cm"1; CI LRMS m/z (ion): 207.25 (M + H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine; In dichloromethane; at 20℃; for 18h; | F3) Synthesis of 5,6-Diazido-hexan-1-ol(i) Hex-5-enyl-1-acetateTo an anhydrous solution of hex-5-en-1-ol (15.0 g, 0.15 mol) in dichloromethane (250 ml) was added acetyl chloride (11.3 ml, 0.20 mol), Triethylamine (20.8 ml, 0.15 ml) was then added and the reaction mixture was stirred at room temperature (18 h) followed by the addition of water (50 ml). The organic layer was separated, the aqueous layer extracted with dichloromethane (2×50 ml) and the combined organic extracts were washed with saturated brine solution (3×100 ml). The organic layer was finally washed with water (3×100 ml) and dried over anhydrous magnesium sulphate. On removal of the drying agent by filtration under gravity, the solvent was removed in vacuo to afford hex-5-enyl-1-acetate as a colourless oil, in near quantitative yield (21.0 g, 99%).deltaH (CDCl3): 1.32 (2H, m) [H3]; 1.53 (2H, m) [H4]; 1.94-1.97 (5H, m) [CH3CO, H2], 3.94 (2H, t, J 6.4 Hz) [H1]; 4.88 (2H, m) [H6]; 5.68 (1H, m) [H5].deltaC (CDCl3): 20.89 [CH3CO]; 25.17 [C3]; 28.02 [C4]; 33.28 [C2]; 64.31 [C1]; 114.78 [C6]; 138.25 [C5]; 171.01 [CO]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With silicon carbide In chlorobenzene at 200℃; for 1h; Microwave irradiation; regioselective reaction; | Procedure for olefin bis-functionalization General procedure: To a chlorobenzene solution (500 µL) of olefin 1a (102 mg, 0.5 mmol) in a 2 mL Pyrex vessel were added ethyl ester 2a (347 µL, 2.5 mmol) and SiC (100 mg). The vessel was sealed, and the reaction mixture was irradiated with microwaves at high absorption level. After being stirred at 200 °C for 1 h, the mixture was filtered through a Celite pad (ether) to remove SiC. The filtrate was concentrated, and the residue was purified with a flash chromatography (SiO2; hexane/ether = 100:1-10:1) to give compound 3aa in 88% yield (173 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tris(2,2'-bipyridyl)ruthenium dichloride; Bromotrichloromethane; sodium L-ascorbate In methanol at 20℃; for 3h; Inert atmosphere; Irradiation; | 2 General procedure for photoredox-initiated thiol-ene click (TEC) reactions General procedure: A 5mL round-bottom flask equipped with a magnetic stir bar and rubber septum was charged with the starting olefin (1mmol, 1.0 equiv) and thiol (3.0mmol, 3 equiv) coupling partners, and sodium ascorbate (0.03mmol, 3mol%). The reaction components were dissolved in MeOH (0.4M). The metal complex Ru(bpy)3Cl2 (0.01mmol, 1mol%) was finally added, and the resultant mixture was degassed by sparging with argon for 15min in the dark. Finally, while stirring at room temperature under an argon atmosphere, BrCCl3 (0.05mmol, 5mol%) was added and the reaction vessel was surrounded by blue LEDs (2W). Powering on of this light source signified reaction commencement. Reactions were typically run for 3h, at, which point the LEDs were powered off and the MeOH removed by rotary evaporation. The reaction mixture was then dissolved in a 7:3 hexanes/ethyl acetate mixture and filtered through a plug of Celite. The crude filtrate was concentrated in vacuo and purified by flash chromatography over SiO2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With (S)-2-{bis[3,5-bis(trifluoromethyl)phenyl][(trimethylsilanyl)oxy]methyl}pyrrolidine; dipotassium hydrogenphosphate; 1,2,3-trimethoxybenzene; dicarbonyl(acetylacotonato)rhodium(I); hydrogen; (2-oxo-1,2-dihydro-6-pyridyl)diphenylphosphine In chloroform at 45℃; for 24h; Autoclave; Inert atmosphere; enantioselective reaction; | Ethyl (2S,3R)-2-tert-Butoxycarbonylamino-3-formyl-8-hydroxyoctanoate(4e) General procedure: Domino Hydroformylation-anti-Mannich Reaction; GeneralProcedureA steel autoclave, equipped with a gas inlet, was charged withK2HPO4 (188 mg, 1.08 mmol, 3.0 equiv) and dried for 15 min underhigh vacuum. Under an inert atmosphere, CHCl3 (0.24 M, 1.35 mL)and a solution of [Rh(CO)2acac] (50 or 100 μL of a stock solutioncontaining 1.8 mg in 400 μL CHCl3) and 6-DPPon (100 or 200 μLof a stock solution containing 5.0 mg in 400 μL CHCl3) were addedsuccessively, followed by addition of the olefin (0.54 mmol, 1.5equiv), organocatalyst 1 (43 mg, 80 μmol, 0.20 equiv), 1,3,5-trimethoxybenzene(9.1 mg, 54 μmol, 0.15 equiv) and α-amido sulfone2 (0.36 mmol, 1.0 equiv). The reaction mixture was saturatedwith synthesis gas (CO/H2, 1:1) by applying three cycles of carefulevacuating and refilling. The autoclave was pressurized with 20 barCO/H2 (1:1) and the mixture was stirred for 24 h at 45 °C. Aftercooling to r.t. and depressurization, the turbid mixture was dilutedwith CH2Cl2, filtered through a plug of silica, and washed withCH2Cl2-Et2O (1:1). The solvent was removed in vacuo and the residuewas purified by flash column chromatography (cyclohexane-EtOAc) to give amino carbonyl compound 4a-l. The enantiomericexcess was determined by chiral HPLC analysis (UV detector);compounds that were not UV active were converted into the correspondingO-benzyloxime and then reduced (see the Supporting Information); Ethyl (2S,3R)-2-tert-Butoxycarbonylamino-3-formyl-8-hydroxyoctanoate(4e)Prepared according to the general procedure with hex-5-en-1-ol(84 μL, 61 mg, 0.54 mmol, 1.5 equiv) and α-amido sulfone 2a(129 mg, 0.360 mmol, 1.0 equiv). Purification was achieved byflash column chromatography (cyclohexane-EtOAc, 5:1).Yield: 99 mg (0.30 mmol, 83%); colorless oil; [α]D22 +26.5(c = 1.30, CHCl3).1H NMR (400 MHz, CDCl3): δ = 1.22 (t, 3JMe-CH2 = 7.2 Hz, 3 H,CH3), 1.42 (s, 3 H, t-Bu), 1.55 (mc, 4 H, CH2), 1.65-1.84 (m, 4 H,CH2), 3.05 (mc, 0.8 H, CH), 2.75* (mc, 0.2 H, CH), 3.60-3.66 (m,2 H, CH2), 4.17 (q, 3JCH2-CH3 = 7.2 Hz, 2 H, CH2), 4.56 (dd, 3JCH-CH =3.7 Hz, 3JCH-NH = 9.4 Hz, 0.8 H, CH), 4.67* (mc, 0.2 H, CH), 5.27(d, 3JNH-CH = 9.2 Hz, 1 H, NH), 9.58 (s, 0.8 H, CHAldehyde), 9.64* (d,3JCH-CH = 1.5 Hz, 0.2 H, CHAldehyde). * = diastereomer.13C NMR (100 MHz, CDCl3): δ = 14.1 (CH3, 1C), 25.0 (CH2, 1C),25.7 (CH2, 1C), 28.3 (CH3, t-Bu, 3C), 30.3 (CH2, 1C), 32.2 (CH2,1C), 46.3 (CH, 1C), 52.1 (CH, 1C), 53.9 (CH, 1C), 61.9 (CH2, 1C),62.6 (CH2-ester, 1C), 171.3 (C, 1C), 202.4 [C(O), 1C], 205.2 [C(O),1C].MS (APCI, +ve): m/z = 232.1 (96), 257.8 (82), 331.8 (100) [M]+,348.8 (72), 654.0 (60).Anal. Calcd for C16H29NO6: C, 57.99; H, 8.82; N, 4.23. Found: C,57.90; H, 8.87; N, 4.06 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With trimethylsilyl trifluoropmethanesulfonate at 20℃; for 2.58333h; Molecular sieve; | |
Stage #1: hex-5-en-1-ol; acetic acid (3aR,5R,6R,7R,7aR)-6-acetoxy-5-acetoxymethyl-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazol-7-yl ester In 1,2-dichloro-ethane at 20℃; for 0.5h; Molecular sieve; Stage #2: With trimethylsilyl trifluoropmethanesulfonate In 1,2-dichloro-ethane at 20℃; Inert atmosphere; Cooling with ice; | 1.1-1c (1-1c) Synthesis of GAL-4 GAL-3 (26.9 g, 81.7 mmol) obtained in step (1-1b)Dissolve in 136ml of anhydrous 1,2-dichloroethane, add 30g of dry molecular sieve powder,Then add 9.0g 5-hexen-1-ol (CAS number: 821-41-0, purchased from Adamas-beta company, 89.9mmol),Stir at room temperature for 30 minutes, add 9.08 g TMSOTf (40.9 mmol) under the protection of ice bath and nitrogen, and stir and react overnight at room temperature.Filter to remove molecular sieve powder, add 300ml dichloroethane to dilute the filtrate, filter with diatomaceous earth,Then add 500ml saturated sodium bicarbonate aqueous solution and stir for 10 minutes to wash, separate the organic phase, and extract the water phase once with 300ml dichloroethane.The organic phases were combined and washed with 300ml saturated sodium bicarbonate aqueous solution and 300ml saturated brine respectively. The organic phase was separated, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain yellow sugar thin product GAL-441.3g, which was directly without purification. Proceed to the next oxidation reaction. | |
With trimethylsilyl trifluoropmethanesulfonate In 1,2-dichloro-ethane at 20℃; Molecular sieve; Inert atmosphere; | 1.1-1c (1-1c) Synthesis of GAL-4 Dissolve the GAL-3 (26.9g, 81.7mmol) obtained in step (1-1b) in 136ml of anhydrous 1,2-dichloroethane, add 30g of dry molecular sieve powder, and then add 9.0g of 5-hexene -1-ol (CAS number: 821-41-0, purchased from Adamas-beta company, 89.9mmol), stirred at room temperature for 30 minutes, added 9.08g TMSOTf (40.9mmol) under ice bath and nitrogen protection, and stirred at room temperature for reaction overnight. The molecular sieve powder was removed by filtration. The filtrate was diluted with 300ml of dichloroethane, filtered with diatomaceous earth, and then added with 500ml of saturated sodium bicarbonate aqueous solution and stirred for 10 minutes to wash, and the organic phase was separated. The aqueous phase was extracted once with 300ml of dichloroethane. The organic phases were combined and washed with 300ml saturated sodium bicarbonate aqueous solution and 300ml saturated brine respectively. The organic phase was separated, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain yellow sugar thin product GAL-441.3g. It was directly without purification. Proceed to the next oxidation reaction. |
Stage #1: hex-5-en-1-ol; acetic acid (3aR,5R,6R,7R,7aR)-6-acetoxy-5-acetoxymethyl-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazol-7-yl ester In 1,2-dichloro-ethane at 20℃; for 0.5h; Molecular sieve; Stage #2: With trimethylsilyl trifluoropmethanesulfonate In 1,2-dichloro-ethane at 20℃; Molecular sieve; Cooling with ice; Inert atmosphere; | 1.1-1-1; 1.1-1-1c (1-1-1c) Synthesis of GAL-4 Dissolve the GAL-3 (26.9g, 81.7mmol) obtained in step (1-1-1b) in 136ml of anhydrous 1,2-dichloroethane, Add 30 g of dry molecular sieve powder, and then add 9.0 g of 5-hexen-1-ol (CAS No. 821-41-0, purchased from Adamas-beta, 89.9 mmol), and stir at room temperature for 30 minutes, Add 9.08 g TMSOTf (40.9 mmol) under ice bath and nitrogen protection, and stir and react overnight at room temperature. Filter to remove molecular sieve powder, add 300ml of dichloromethane to the filtrate to dilute, filter with diatomaceous earth, then add 500ml of saturated sodium bicarbonate aqueous solution and stir for 10 minutes to wash. Separate the organic phase, extract the aqueous phase with 300ml of dichloroethane once, combine the organic phases and wash with 300ml of saturated aqueous sodium bicarbonate solution and 300ml of saturated brine, respectively. Separate the organic phase, dry with anhydrous sodium sulfate, and evaporate the solvent under reduced pressure to obtain a yellow sugar thin product GAL-441.3g, and proceed directly to the next oxidation reaction without purification. | |
In dichloromethane Molecular sieve; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With p-phenylpyridine In dichloromethane at 20℃; for 20h; Inert atmosphere; UV-irradiation; | General Procedure for ATRA General procedure: A Pyrex test tube(12.5 cm × 1.6 cm) containing a mixture of alkene 1 (1.75equivalent (equiv), 0.175 mmol), α-bromo carbonyl 2 (1.0 equiv,0.1 mmol) and 4-phenylpyridine (0.05 equiv, 0.005 mmol) indichloromethane (0.5 mL) was degassed via FPT cycling forthree times and backfilled with Ar. The tube was placedapprox. 0.5 cm from 3W 380 nm LED. The resulting solutionwas stirred at ambient temperature for 20 h. The residue wasconcentrated in vacuo. The resulting mixture was purified byflash column chromatography on silica gel to give product 3. |
80% | With bismuth(III) oxide In dimethyl sulfoxide at 20℃; for 24h; Sealed tube; Inert atmosphere; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | To a solution of the 5-hexene-1-ol (1.84 g, 18.0 mmol) in dimethylformamide (40 mL), was added at room temperature NaH (60% dispersion in oil, 0.72 g, 18 mmol) in two portions. After stirring the reaction mixture at room temperature for 30 minutes, a solution of 2,4- dimethylbenzyl methanesulfonate (2.57 g) in dimethylformamide (20 mL) was added dropwise. The reaction mixture was thereafter stirred at room temperature for an additional18 hours. Water was then added (100 mL) and the reaction mixture was stirred for 5 minutes before extraction with ethyl acetate (100 mL) was performed. The organic phases were washed with brine (2x100 mL), dried over anhydrous sodium sulfate and concentrated at reduced pressure. The title compound was purified by column chromatography (hexane to hexane/ethyl acetate 95:5) and was isolated in 1.68 g (61%) yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | Stage #1: 3-Hydroxy-2-naphthoic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 20℃; Inert atmosphere; Stage #2: 5-Hexen-1-ol With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 20℃; for 24h; Inert atmosphere; | General Procedure for the Synthesis of Alkenyl 3-Hydroxy-2-naphthoates (3a-3h) from Primary Alcohols General procedure: N,N'-Carbonyldiimidazole (CDI, 80 mmol) was added to a solution of 3-hydroxy-2-naphthoic acid (80 mmol) in DMF (70 mL) for 10-15 min while stirring at 20°C in an argon atmosphere. The reaction occurred with evolution of CO2. After the whole amount of CDI was added, the stirring of the reaction mixture (solution I) was continued for another 1 h. A mixture of alkenol (53.1 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 79.7 mmol) was stirred in DMF (60 mL) (solution II) under the same conditions as indicated above. Then solution II was added to solution I at 20°C; the resulting reaction mixture was stirred for 24 h at the same temperature. The reaction mixture was diluted with diethyl ether (150 mL) and washed in sequence with a 10% HCl solution (4 × 50 mL), H2O (3 × 50 mL) until neutral pH of the medium, and then with a saturated NaHCO3 solution (3 × 50 mL) and H2O (3 × 50 mL)until neutral pH of the medium. The organic layer was dried over MgSO4. The solvent was removed at reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With dmap; triethylamine In dichloromethane at 20℃; for 3h; Cooling with ice; | 13 5-Hexene-1-ol (30.1 g, 0.3 mol) was dissolved in 100 ml of methylene chloride, 33.4 g (0.33 mol) of triethylamine, N, N-dimethylaminopyridine 1.8 g (0.015 mol) was added, and this solution was cooled with ice. Next, to the ice-cooled solution, a methylene chloride solution in which 31.4 g (0.3 mol) of methacrylic acid chloride was dissolved in methylene chloride (50 ml) was added dropwise. The solution obtained after completion of the dropwise addition was stirred at room temperature for 3 hours and then added dropwise to distilled water And the mixture was further extracted three times with methylene chloride. The solvent was removed from the methylene chloride layer obtained by the extraction using a rotary evaporator to obtain a residue. Further, the obtained residue was dissolved in 100 ml of toluene. The obtained toluene solution was washed three times with 0.5 N hydrochloric acid solution, then washed with saturated brine solution three times and dried with magnesium sulfate solution. After drying, the magnesium sulfate solution was filtered off, the filtrate was concentrated with a rotary evaporator, and the concentrate was vacuum dried further to obtain 46.4 g (yield 92%) of 5-hexen-1-yl methacrylate |
92% | With dmap; triethylamine In dichloromethane at 20℃; for 3h; Cooling with ice; | 5-Hexene-1-ol (30.1 g, 0.3 mol) was dissolved in 100 ml of methylene chloride,33.4 g (0.33 mol) of triethylamine,A solution prepared by adding 1.8 g (0.015 mol) of N, N-dimethylaminopyridine was prepared,Further, this solution was ice-cooled.next,To the ice-cooled solution,A methylene chloride solution in which 31.4 g (0.3 mol) of methacrylic acid chloride was dissolved in methylene chloride (50 ml) was added dropwise.After completion of the dropwise addition,After stirring at room temperature for 3 hours,100 ml of distilled water was added,It was further extracted three times with methylene chloride.The solvent was removed from the methylene chloride layer obtained by the extraction using a rotary evaporator to obtain a residue.further,The obtained residue was dissolved in 100 ml of toluene.The obtained toluene solution was washed three times with 0.5 N hydrochloric acid solution,Washed three times with saturated saline solution,And dried with magnesium sulfate solution.After drying, magnesium sulfate solution was filtered off,The filtrate was concentrated on a rotary evaporator,The concentrate was further dried under vacuum,46.4 g (yield 92%) of 5-hexen-1-yl methacrylate was obtained. |
91% | With dmap; triethylamine In dichloromethane at 20℃; |
With triethylamine In tetrahydrofuran at 0 - 20℃; | 3 Example 3 - Hex-5-en-1-yl methacrylate The synthesis of hex-5-en-l-yl methacrylate was performed in accordance with a published procedure, see DOI: 10.1021/ma00174a057 and DOI: 10.1021/ma0714619. The reaction yielded 23.2 mmol crude hex-5-en-l-yl methacrylate (76% of theory) as a viscous yellow oil, which was used without purification for the next step. The recorded NMR spectra was found to agree with the data reported in the literature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 22℃; for 12h; | General procedure: A solution of alkynol/enol (10 mmol, 1.0 equiv) in CH2Cl2 (10 mL) was slowlyadded via cannula to a solution of dicyclohexylcarbodiimide (DCC) (12 mmol, 1.2 equiv),4-dimethylaminopyridine (DMAP) (1 mmol, 0.1 equiv) and carboxylic acid (10.5 mmol, 1.05 equiv)in CH2Cl2 (100 mL) at 22 C. After stirring for 12 h at the same temperature, the reaction mixturewas filtrated, and the filtrate was concentrated. The residue was subsequently purified by silica gelflash chromatography to provide compounds 1 or 6b. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | 3.06 g (20 mmol) of phosphorus oxychloride and 40 mL of dichloromethane were placed in an eggplant flask (300 mL), and the mixture was stirred at 0 C. 20 mL of a mixed dichloromethane solution of 200 mg (2 mmol) of 5-hexen-1-ol and 158 mg (2 mmol) of pyridine was slowly added dropwise and the mixture was stirred at 0 C. for 1 hour and at room temperature for 1 hour. Excess of phosphorus oxychloride and dichloromethane were distilled off and dried under reduced pressure. To the obtained crude phosphoric acid chloride was added 40 mL of pyridine, and the mixture was stirred at 0 C. 2.76 g (10 mmol) of Corinthsirat was added while thoroughly stirring, and the mixture was stirred at room temperature for 24 hours. Water (20 mL) was added to the reaction solution, and the mixture was further stirred at room temperature for 6 hours. Pyridine and water were distilled off, and the objective substance was purified by performing silica gel column (methanol: chloroform = 100: 100 ? 0) twice. Colorless solid Yield 34% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: 5-Hexen-1-ol With pentafluorophenylboronic acid; oxalic acid In nitromethane at 20℃; for 0.0833333h; Stage #2: 1-(2-methoxyphenyl)ethanol In nitromethane at 20℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With pyridine; In dichloromethane; at 0 - 20℃; for 24h;Inert atmosphere; | General procedure: To a 250 mL flame dried Schlenk flask, 1.0 equiv (2.95 g, 10 mmol)of 4,4?-oxybis (benzoyl chloride) dissolved in 80 mL of dry CH2Cl2 was added with stirring under nitrogen atmosphere. The solution was cooled to 0 C and then 2.1 equiv of the 10-undecen-1-ol (3.58 g, 21 mmol) and 2.1 equiv of pyridine (1.66 g, 21 mmol) were slowly added to the solution via syringe. The mixture was allowed to warm to room temperature for 24 h and quenched with addition of 1M HCl (100 mL) and deionized water (100 mL). The organic layer was dried over anhydrous Mg2SO4, filtered, concentrated in vacuum, and purified by column chromatography using n-hexane/ethyl acetate (7/1) as an eluent to yield a white solid. (yield=83%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; (S,S)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane In toluene at 100℃; for 2h; | Preparation of 4-(4,5-diphenyl-2,3-dihydroselenophen-3-yl)butan-1-ol In toluene solvent (1 mL)[Rh (COD) Cl] 2 (4.93 mg, 0.01 mmol) and (S,S)-DIOP (12.0 mg, 0.024 mmol), 4,5-diphenyl-1,2,3-selenadiazole (57.04 mg, 0.2 mmol ), hex-5-en-1-ol) 0.072 mL, 0.6 mmol) and then reacted at 100 oC for 2 hours. After the reaction is completed, the solvent is removed using an evaporator. The column (Ether: DCM: Hexane = 1: 2: 3) was then run to obtain the desired compound, 4-(4,5-Diphenyl-2,3-dihydroselenophen-3-yl)butan-1-ol. (65.1 mg, 91%) was obtained. |
91% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; (S,S)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane In toluene at 100℃; for 2h; | Preparation of 4-(4,5-diphenyl-2,3-dihydroselenophen-3-yl)butan-1-ol [Rh(COD)Cl]2 (4.93 mg, 0.01 mmol) and (S,S)-DIOP (12.0 mg, 0.024 mmol) in toluene solvent (1 mL),4,5-diphenyl-1,2,3-selenadiazole (57.04 mg, 0.2 mmol),After adding hex-5-en-1-ol 0.072 mL, 0.6 mmol), react at 100 °C for 2 hours. After completion of the reaction, the solvent is removed using an evaporator. Then, proceed to the column (Ether: DCM: Hexane = 1: 2: 3) to obtain the desired compound, 4-(4,5-Diphenyl-2,3-dihydroselenophen-3-yl)butan-1-ol (65.1 mg, 91 %). |
91% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; (S,S)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane In toluene at 100℃; for 2h; | 2 Preparation of 4-(4,5-Diphenyl-2,3-dihydroselenophen-3-yl)butan-1-ol [Rh(COD)Cl]2(4.93 mg, 0.01 mmol) and (S,S)-DIOP in toluene solvent (1 mL)(12.0 mg, 0.024 mmol), 4,5-diphenyl-1,2,3-selenadiazole(57.04 mg, 0.2 mmol), hex-5-en-1-ol) 0.072 mL, 0.6 mmol) was added, and then reacted at 100oC for 2 hours.After completion of the reaction, the solvent is removed using an evaporator. And the column(Ether: DCM: Hexane = 1: 2: 3)4-(4,5-Diphenyl-2,3-dihydroselenophen-3-yl)butan-1-ol(65.1 mg, 91%) could be obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22.2% | With triethylamine In dichloromethane at 0 - 20℃; | 3-Bromopropionyl chloride (5.00 g, 29.0 mmol) was added dropwise to a solution of 5-hexen-1-ol (2.70 g, 27.0 mmol) and triethylamine (4.00 mL, 28.6 mmol) in dichloromethane (100 mL) at 0 °C. After the addition was completed, the mixture was stirred at room temperature overnight. The organic phase was washed with H2O (50 mL) and then dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the crude product was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate (petroleum ether/ethyl acetate = 250:1 and then 200:1) as the eluent to furnish the product hex-5-en-1-yl 3-bromopropanoate as a colorless liquid (1.41 g, 22.2% yield). 1H NMR (500 MHz, CDCl3) δ 5.79 (ddt, J = 16.9, 10.2, 6.7 Hz, 1H), 5.05-4.95 (m,2H), 4.14 (t, J = 6.6 Hz, 2H), 3.58 (t, J = 6.8 Hz, 2H), 2.92 (t, J = 6.8 Hz, 2H), 2.13-2.05 (m,2H), 1.66 (dt, J = 14.9, 6.7 Hz, 2H), 1.47 (dq, J = 15.1, 7.6 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.9% | With phosphotungstic acid; dodecatungstosilic acid In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 16h; | 3 Example 2 Equipped with a thermometer, reflux condenser, Add 87.5 grams of 2-bromo-2,2-difluoroacetic acid, 43 grams of 5-hexen-1-ol, 8.75 grams of phosphotungstic acid, 8.75 grams of silicotungstic acid and 500 grams of xylene, The reaction was refluxed at 140°C until no water was released, and the reaction time was 16 hours. After the reaction is completed, the solvent is distilled to recover, and then the fraction under the condition of 159160/40mmHg is collected by vacuum distillation. Obtain 2-bromo-2,2-difluoroacetic acid allylhexyl ester 124.5 g, yield 96.9%, purity 99.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With iron(III)-acetylacetonate; phenylsilane In ethanol; ethylene glycol at 35℃; for 12h; Schlenk technique; Inert atmosphere; | 4.2. General Procedures of Iron-Catalyzed SOMOphilic Alkynylation General procedure: Flame-dried 10 mL Schlenk tube filled with N2, acetylenic sulfones 2 (0.2 mmol, 1.0 equiv) and Fe(acac)3 (21.2 mg, 0.06 mmol, 30 mol%) were added under N2, evacuated and purged with N2 three times. Afterwards, PhSiH3 (43.2 mg, 0.4 mmol, 2 equiv), nonactivted alkenes 1 (33.1 mg, 0.3 mmol, 1.5 equiv) and ethanol (0.8 mL) and ethylene glycol (0.2 mL) were added via syringe. The formed mixture was stirred at 35 °C under N2 for 12 h, as monitored by TLC. The solution was then cooled to room temperature, and the solution was diluted with ethyl acetate and transferred to a round bottom flask. The concentrated residue was purified by column chromatography using ethyl acetate/petroleum ether as an eluent to afford the corresponding products and 3 and 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With iron(III)-acetylacetonate; phenylsilane In ethanol; ethylene glycol at 35℃; for 12h; Schlenk technique; Inert atmosphere; | 4.2. General Procedures of Iron-Catalyzed SOMOphilic Alkynylation General procedure: Flame-dried 10 mL Schlenk tube filled with N2, acetylenic sulfones 2 (0.2 mmol, 1.0 equiv) and Fe(acac)3 (21.2 mg, 0.06 mmol, 30 mol%) were added under N2, evacuated and purged with N2 three times. Afterwards, PhSiH3 (43.2 mg, 0.4 mmol, 2 equiv), nonactivted alkenes 1 (33.1 mg, 0.3 mmol, 1.5 equiv) and ethanol (0.8 mL) and ethylene glycol (0.2 mL) were added via syringe. The formed mixture was stirred at 35 °C under N2 for 12 h, as monitored by TLC. The solution was then cooled to room temperature, and the solution was diluted with ethyl acetate and transferred to a round bottom flask. The concentrated residue was purified by column chromatography using ethyl acetate/petroleum ether as an eluent to afford the corresponding products and 3 and 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 16.5h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With bis(3,5-di-(tert-butyl)-2-hydroxyazobenzolato)nickel(II); potassium-t-butoxide In toluene at 120℃; for 24h; Inert atmosphere; |
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