Structure of 143825-84-7
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| CAS No. : | 143825-84-7 |
| Formula : | C14H19BO2 |
| M.W : | 230.11 |
| SMILES Code : | C=C(B1OC(C)(C)C(C)(C)O1)C2=CC=CC=C2 |
| English Name : | 4,4,5,5-Tetramethyl-2-(1-phenylvinyl)-1,3,2-dioxaborolane |
| MDL No. : | MFCD06659923 |
| InChI Key : | RMGBWPMWUZSIMH-UHFFFAOYSA-N |
| Pubchem ID : | 11031671 |
| Num. heavy atoms | 17 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.43 |
| Num. rotatable bonds | 2 |
| Num. H-bond acceptors | 2.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 72.32 |
| TPSA ? Topological Polar Surface Area: Calculated from |
18.46 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.94 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.33 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.19 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.4 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.37 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-3.88 |
| Solubility | 0.0305 mg/ml ; 0.000132 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-4.03 |
| Solubility | 0.0216 mg/ml ; 0.0000939 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.45 |
| Solubility | 0.00816 mg/ml ; 0.0000355 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
Yes |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.91 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<2.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.8 |
* 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 |
|---|---|---|
| 88% | With triphenylphosphine In toluene mixt. in toluene stirred at 50°C for 5 h; treated (H2O) at room temp.; extd. (benzene); washed with brine; dried (MgSO4); purified by chromy. on silica gel or by distn. (vac.); | |
| 53.2% | With bis-triphenylphosphine-palladium(II) chloride; sodium phenoxide; triphenylphosphine; potassium bromide In toluene at 70℃; for 16h; Inert atmosphere; | 1-4 General procedure: Add sodium phenolate PhONa (95.13g) to the mixture of (1-bromovinyl)benzene, which is raw material 1 (100g, 0.548mol) and biborate, which is raw material 2 (153.11g, 0.603mol), and toluene solvent (1L). , 0.82mol), KBr (97.52g, 0.82mol), triphenylphosphine PPh3 (4.31g, 16.44mmol) and dichlorobis(triphenylphosphino)palladium Pd(PPh3)2Cl2 (7.68g, 10.96mmol). Stir for 16 hours under the protection of inert gas at 70°C. TLC (petroleum ether: ethyl acetate = 15:1) showed that the raw material 1 ((1-bromovinyl)benzene) was consumed and new compounds were formed. After the reaction mixture was filtered, the filtrate was concentrated under reduced pressure to remove the solvent. The concentrated solution was diluted with water and extracted with ethyl acetate solvent. The extracted organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to obtain a crude product. Then dilute the crude product with petroleum ether and ethyl acetate, stir for several hours, filter, collect the filtrate and concentrate to obtain a solid. The solid was recrystallized with petroleum ether at 0°C to obtain the final product, which was a yellow solid (64.28 g, 0.279 mol, yield 51.1%). |
| 88 % Chromat. | With potassium phenolate; triphenylphosphine In toluene at 50℃; for 5h; |
| 88 % Chromat. | With potassium phenolate; triphenylphosphine In toluene at 50℃; for 5h; | |
| With C6H5OK In toluene mixt. of alkene, B compound, base, Pd catalyst and PPh3 was stirred at 50°C for 5 h; Kugelrohr distn. or chromy. on silica gel; 88% GC yield; | ||
| With bis-triphenylphosphine-palladium(II) chloride; potassium phenolate; triphenylphosphine In toluene at 50℃; | ||
| With bis-triphenylphosphine-palladium(II) chloride; potassium phenolate; triphenylphosphine In toluene at 50℃; for 5h; Inert atmosphere; | 92.1 Step 1. 4.4.5.5-tetramethyl-2-(1-phenylethenyl)-1 ,3.2-dioxaborolane Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen was added (l-bromoethenyl)benzene (800 mg, 4.370 mmol, 1.00 equiv), 4,4,5,5-tetramethyl-2-(tetramethyl-1 ,3,2-dioxaborolan-2-yl)- 1 ,3,2-dioxaborolane (1.23 g, 4.840 mmol, 1.11 equiv), potassium phenolate (870 mg, 6.580 mmol, 1.51 equiv), Pd(PPh3)2Cl2 (92 mg, 0.080 mmol, 0.02 equiv), PPhi3 (69 mg, 0.260 mmol, 0.06 equiv) and toluene (15 ml_). The resulting mixture was stirred for 5 h at 50 °C in an oil bath and then concentrated under vacuum. The residue was dissolved in ethyl acetate and washed with water (10 ml_) and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (5:95) to yield 4,4,5,5-tetramethyl-2-(1-phenylethenyl)-1 ,3,2-dioxaborolane as brown oil. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 99% | With triphenylphosphine In toluene mixt. in toluene stirred at 50°C for 4 h; treated (H2O) at room temp.; extd. (benzene); washed with brine; dried (MgSO4); purified by chromy. on silica gel or by distn. (vac.); | |
| 99 % Chromat. | With potassium phenolate; triphenylphosphine In toluene at 50℃; for 4h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With triethylamine In tetrahydrofuran at 25℃; for 14h; Title compound not separated from byproducts.; | ||
| With Ru(at)TBAB at 85℃; for 23h; Inert atmosphere; stereoselective reaction; | 2.3. General procedure for phenylacetylene hydroboration Pinacolborane (1.0 mmol) and then phenylacetylene (1.0 mmol)were added under argon to the M(at)OS (0.1 mol%) contained in a15 mL reaction tube. The mixture was stirred at 85°C for 23 h.The reaction mixture was then diluted in dichloromethane andfiltrated over a pad of silica. After washing twice with 10 mLof dichloromethane the filtrate was concentrated under vacuumto give the corresponding vinylborane as a mixture of isomers.Product distribution was determined by GC/MS. Conversion isdetermined using the relative areas in GC/MS and according tomesitylene as internal standard. The spectral data were in agree-ment with those reported in the literature. | |
| With [Rh(CO)(2-pyridyldiphenylphosphine)(2-iodo-3,4,5,6-tetrafluorophenyldiphenylphosphine)]BARF In dichloromethane-d2 at 20℃; for 24h; Inert atmosphere; Overall yield = 88 %Spectr.; |
| With PhboxmiCo(CH2SiMe3) In hexane; toluene at 20℃; for 15h; Overall yield = 64 percent; regioselective reaction; | ||
| 28 %Chromat. | With C78H66N10(4+)*4F6P(1-); cobalt(II) chloride; sodium t-butanolate In tetrahydrofuran at 20℃; for 16h; Inert atmosphere; Schlenk technique; Glovebox; | |
| 1: 78 %Chromat. 2: 8 %Chromat. | With potassium <i>tert</i>-butylate In dimethyl sulfoxide at 25℃; Inert atmosphere; Glovebox; Schlenk technique; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With C32H12BF24(1-)*C33H43IrN2OP(1+); hydrogen In dichloromethane at 20℃; for 18h; optical yield given as %ee; enantioselective reaction; | ||
| With C32H12BF24(1-)*C35H38IrN2PS(1+); hydrogen In dichloromethane at 20℃; for 18h; optical yield given as %ee; enantioselective reaction; | ||
| Multi-step reaction with 2 steps 1: Rh/C; hydrogen / toluene / 4 h / 20 °C 2: phosphite dehydrogenase; recombinant phenylacetone monooxygenase from Thermobifida fusca; NADPH / dimethyl sulfoxide / 5 h / 30 °C / pH 7.5 / Tris/HCl buffer; Enzymatic reaction |
| Multi-step reaction with 2 steps 1: Rh/C; hydrogen / toluene / 4 h / 20 °C 2: phosphite dehydrogenase; recombinant phenylacetone monooxygenase from Thermobifida fusca; NADPH / dimethyl sulfoxide / 3 h / 30 °C / pH 9 / Tris/HCl buffer; Enzymatic reaction | ||
| With C32H12BF24(1-)*C36H57IrN2OP(1+); hydrogen In dichloromethane at -20℃; for 4h; Autoclave; optical yield given as %ee; enantioselective reaction; | ||
| Multi-step reaction with 2 steps 1: Rh/C; hydrogen / toluene 2: phosphite dehydrogenase; phosphite; recombinant Thermobifida fusca phenylacetone monooxygenase M446G mutant; oxygen; NADPH / dimethyl sulfoxide / 4 h / 30 °C / pH 7.5 / aq. buffer; Enzymatic reaction | ||
| Multi-step reaction with 2 steps 1: Rh/C; hydrogen / toluene 2: phosphite dehydrogenase; phosphite; recombinant Thermobifida fusca phenylacetone monooxygenase; oxygen; NADPH / dimethyl sulfoxide / 5 h / 30 °C / pH 7.5 / aq. buffer; Enzymatic reaction | ||
| 88 % ee | With C49H45IrN2O3P(1+)*C32H12BF24(1-); hydrogen In dichloromethane at 20℃; for 4h; | |
| 74 % ee | With C50H59IrO4PS(1+)*C32H12BF24(1-); hydrogen In dichloromethane for 4h; Autoclave; enantioselective reaction; | |
| 82 % ee | With C42H63IrO3PS(1+)*C32H12BF24(1-); hydrogen In dichloromethane Autoclave; High pressure; | |
| 58 % ee | With C34H41IrOPS(1+)*C32H12BF24; hydrogen In dichloromethane Autoclave; High pressure; | |
| 86 % ee | With C47H56IrNO4PSi2(1+)*C32H12BF24(1-); hydrogen In dichloromethane at 20℃; for 4h; Autoclave; enantioselective reaction; | |
| 25 % ee | With C49H52IrNO4PSi2(1+)*C32H12BF24(1-); hydrogen In dichloromethane at 20℃; for 4h; Autoclave; enantioselective reaction; | |
| 60 % ee | With [Ir(COD)2]BArF; C39H50NO7PSi2; hydrogen In dichloromethane at 20℃; for 4h; Schlenk technique; Autoclave; enantioselective reaction; | |
| 49 % ee | With bis(norbornadiene)rhodium(l)tetrafluoroborate; ZhaoPhos; hydrogen In dichloromethane at 30℃; for 6h; Autoclave; Overall yield = 76 %; Overall yield = 17.6 mg; enantioselective reaction; | |
| 44 % ee | With C32H12BF24(1-)*C43H59IrO3PS(1+); hydrogen In dichloromethane at 20℃; for 16h; Autoclave; Schlenk technique; | |
| 74 % ee | With C32H12BF24(1-)*C31H37IrOPS(1+); hydrogen In dichloromethane at 20℃; for 16h; Autoclave; Schlenk technique; | |
| 80 % ee | With C23H43IrN2OP(1+)*C32H12BF24(1-); hydrogen In dichloromethane at 23℃; enantioselective reaction; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 58% | With potassium carbonate In 1,4-dioxane at 100℃; for 3h; Inert atmosphere; | 81 Example 81 (4R,6R,7S)-4,7-dfftert-butyldimethylsilyloxy)-2-(1-phenylvinyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-4,6-carbolactone (7). A Shlenck tube was charged with iodide VII of example 37 (190 mg, 0.34 mmol), Pd(PPh3)4 (40 mg, 0.03 mmol) and dry dioxane (3.4 mL). Anhydrous K2CO3 (0.92 mL, 1.01 mmol, 1.1 M) and 1-phenylvinylboronic acid pinacol ester (116 mg, 0.50 mmol) was then added and the resultant solution was deoxygenated and heated at 100° C. for 3 h. After cooling to room temperature, the reaction mixture was filtered through a plug of Celite and the precipitate was washed with hexane. The filtrate and the washings were concentrated and the obtained residue was purified by columm chromatography, previously neutralized with 5% triethylamine-hexanes, eluting with diethyl ether-hexanes (5:95) to yield thiophene 7 (105 mg, 58%) as a light yellow oil. [α]D20=-46.6° (c1.9, in CHCl3). 1H NMR (250 MHz, CDCl3) δ 6.88-6.85 (m, 5H, 5*ArH), 6.86 (s, 1H, H-2), 5.56 (s, 1H), 5.26 (s, 1H), 4.86 (d, J=3.2 Hz, 1H, H-7), 4.67 (dd, J=5.6 and 3.2 Hz, 1H, H-6), 2.61 (d, J=10.9 Hz, 1H, H-5ax), 2.51 (dd, J=10.9 and 5.8 Hz, 1H, H-5eq), 0.94 (s, 9H, C(CH3)3), 0.89 (s, 9H, C(CH3)3), 0.23 (s, 3H, CH3), 0.21 (s, 3H, CH3), 0.20 (s, 3H, CH3) and 0.11 (s, 3H, CH,) ppm. 13C NMR (63 MHz, CDCl3) δ 175.1 (C), 145.3 (C), 143.1 (C), 141.7 (C), 140.2 (C), 134.0 (C), 128.2 (2*CH), 128.1 (3*CH), 122.4 (CH), 114.0 (CH2), 77.2 (CH), 75.3 (C), 66.3 (CH), 37.8 (CH2), 25.7 (C(CH3)3), 25.5 (C(CH3)3), 18.1 (C(CH3)3), 18.0 (C(CH3)3), -3.0 (CH3), -3.2 (CH3), -4.6 (CH3) and -4.6 (CH3) ppm. IR (film) 1803 (C=O) cm-. MS (ESI) m/z (%) 543 (MH+). HRMS calcd for C29H43O4SSi2 (MH+): 543.2415; found, 543.2412. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 75% | With diethylzinc In dichloromethane | |
| 92 % | Stage #1: diiodomethane With diethylzinc In dichloromethane; toluene at 0℃; Inert atmosphere; Stage #2: 4,4,5,5-tetramethyl-2-(1-phenylvinyl)-1,3,2-dioxaborolane In dichloromethane; toluene at 0℃; Inert atmosphere; | 17.1 17.1 Synthesis of compound L017-1 At room temperature, diiodomethane (5.9g, 21.72mmol) was added to dichloromethane (40mL), cooled to 0°C, and after stirring for 5 minutes under a nitrogen atmosphere, a toluene solution of diethylzinc (10.8mL, 10.8mmol, 1M toluene solution), the reaction solution was stirred at 0°C for 0.5 hours.Then, a solution of L017-a (1 g, 4.35 mmol) in dichloromethane (10 mL) was slowly added dropwise, and the reaction solution was continued to stir at 0°C for 0.5 hours, and then the temperature was raised to room temperature and stirred for 16 hours.Add saturated aqueous ammonium chloride solution (50 mL) to the reaction solution to quench, and stir for 3 to 5 minutes.Extract with dichloromethane (50 mL×3), wash the combined organic phases with saturated brine (50 mL), dry over anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure.The residue was purified by silica gel column chromatography to obtain compound L017-1 (979 mg, yield 92%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | With caesium carbonate In 1,4-dioxane; water at 80℃; for 6h; Inert atmosphere; | Intermediate 25; 3,4-bis(BenzyIoxy)-6-(l-phenylethenyl)pyridazine General procedure: Intermediate 25; 3,4-bis(BenzyIoxy)-6-(l-phenylethenyl)pyridazine A mixture of 3,4-bis(benzyloxy)-6-chloropyridazine (Intermediate 1: 3 g. 9.18 mmol), dioxane (32.1 ml) and water (9.64 ml) was degassed and to this was added mono(bis(di- tert-butyl(4-(dimethylamino)phenyl)phosphonio)palladium(IV)) dichloride (0.195 g, 0.275 mmol), cesium carbonate (10.14 g, 31.1 mmol) and 4,4,5>5-tetramefhyl-2-(l- phenylethenyl)-l,3,2-dioxaborolane (3 g, 13.04 mmol). The mixture was heated to 80 °C for 6 hours and upon cooling was partitioned between dichloromethane and water.The organic portion was dried (MgS ), filtered and concentrated to give an orange oil. The crude oil was purified by silica chromatography eluting with 0-60 % ethyl acetate in petrol to afford 3,4-bis(benzyloxy)-6-(l-phenylethenyl)pyridazine as a brown oil (yield = 91 %). Ή NMR (400 MHz, CHCl3-d) δ 7.54 - 7.66 (m, 2 H), 7.24 - 7.44 (m, 13 H), 6.72 (s, 1H), 6.02 (s, 1H), 5.70 (s, 2H), 5.63 (s, 1H), 5. 1 (s, 2H). MS ES+: 395. |
| 91% | With bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II); caesium carbonate In 1,4-dioxane; water at 80℃; for 6h; | Intermediate 25: 3,4-bis(Benzyloxy)-6-(1-phenylethenyl)pyridazine Intermediate 25: 3,4-bis(Benzyloxy)-6-(1-phenylethenyl)pyridazine[0310][0311]A mixture of 3,4-bis(benzyloxy)-6-chloropyridazine (Intermediate 1: 3 g, 9.18 mmol), dioxane (32.1 ml) and water (9.64 ml) was degassed and to this was added mono(bis(di-tert-butyl(4-(dimethylamino)phenyl)phosphonio)palladium(IV))dichloride (0.195 g, 0.275 mmol), cesium carbonate (10.14 g, 31.1 mmol) and 4,4,5,5-tetramethyl-2-(1-phenylethenyl)-1,3,2-dioxaborolane (3 g, 13.04 mmol). The mixture was heated to 80° C. for 6 hours and upon cooling was partitioned between dichloromethane and water. The organic portion was dried (MgSO4), filtered and concentrated to give an orange oil. The crude oil was purified by silica chromatography eluting with 0-60% ethyl acetate in petrol to afford 3,4-bis(benzyloxy)-6-(1-phenylethenyl)pyridazine as a brown oil (yield=91%).[0312]1H NMR (400 MHz, CHCl3-d) δ 7.54-7.66 (m, 2H), 7.24-7.44 (m, 13H), 6.72 (s, 1H), 6.02 (s, 1H), 5.70 (s, 2H), 5.63 (s, 1H), 5.11 (s, 2H).[0313]MS ES+: 395. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 90℃; for 18h; Inert atmosphere; | 78.2; 88.2 Tert-butyl 2-methyl-4-(l-phenylvinyl)benzoate. Tert-butyl 2-methyl-4-(l-phenylvinyl)benzoate. To a solution of tert-butyl 4- bromo-2-methylbenzoate (2 g, 7 mmol) in dioxane/water (50 mL, 4: 1) was added styrylboronic acid pinacol ester (1.64 g, 7 mmol), tetrakis(triphenylphosphine)palladium (0.7 mmol, 0.904 g), sodium carbonate (21 mmol, 2.3 g). The mixture was stirred at 90 °C under nitrogen gas atmosphere for 18 hours. LC-MS showed the start material has been consumed. Then evaporated the solvent and purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 30: 1) to give tert-butyl 2-methyl-4-(l-phenylvinyl)benzoate (1.8 g, 91%). 1H-NMR (300 MHz, CD3OD) δ 7.80 (d, J = 8.1 Hz, 1H), 7.32-7.19 (m, 5H), 7.18 (s, 2H), 5.49 (t, J = 3.3 Hz, 2H), 2.56 (s, 3H), 1.60 (s, 9H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 89% | With tetrabutylammonium acetate In neat (no solvent) at 90℃; for 20h; Inert atmosphere; Schlenk technique; | |
| 81% | With copper(I) thiophene-2-carboxylate; Xantphos; sodium t-butanolate In toluene at 20℃; for 24h; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 77% | With bis(tri-t-butylphosphine)palladium(0); diisopropylamine In toluene at 80℃; for 24h; Inert atmosphere; | Compound 6a General procedure: 1,8-Diiodoanthracene (4, 3.00 g, 6.98mmol) was dissolved in a mixture of degassed toluene (70 mL)and diisopropylamine (3.92 mL, 27.9mmol). To the solution were added 5a (3.58 mL, 20.9mmol) and [Pd(PtBu3)2] (357 mg, 0.699mmol). The reaction mixture was heated at 80 °C for 24 h under Ar. After the mixture was filtered through Celite, the filtrate was evaporated. The crude product was purified by chromatography on silica gel with toluene/CH2Cl2 1:1 eluent to give the desired compound as black oil. Yield 2.89 g (86%) |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 67% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In N,N-dimethyl-formamide at 80℃; for 18h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 57% | With water; potassium carbonate In dichloromethane at 100℃; for 12h; Sealed tube; Inert atmosphere; | 2.5 Example 5 Preparation of 1-phenyl-2-phenylethyleneboronic acid pinacol ester Weighed diphenyl iodonium triflate (0.5 mmol, 215 mg), potassium carbonate (0.5 mmol, 69 mg)In a 25 mL sealed tube, a magnetic charge was added, and after replacing the air in the sealed tube three times with high-purity nitrogen, 1-phenyl-1-vinylboronic acid pinacol ester (1 mmol, 230 mg) was added to the sealed tube under nitrogen protection. 2.5 mL of dichloromethane, deionized water (20 mmol, 333 μl)The tube was tightly sealed, transferred to an oil bath at 100 ° C and stirred for 12 h. TLC detection and tracking reaction, after the reaction is over, willThe tube was cooled to room temperature. Add 5 mL of distilled water to the system to quench the reaction, stir; extract 3 times with 5 mL of dichloromethane, and combineThe machine phase was dried over magnesium sulfate, and the solvent was removed by a rotary evaporator to obtain a crude product; the crude product was loaded on silica gel, eluentAfter purification by column chromatography using a volume ratio of petroleum ether: ethyl acetate = 50:1The pure 1-phenyl-2-phenylethylene boronic acid pinacol ester was obtained as a white solid, and the isolated yield was 57%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 50% | With potassium phosphate; palladium diacetate; tricyclohexylphosphine In toluene at 100℃; | 72 Synthesis of (S)-N-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethyl)-3-(1-phenylvinyl)isonicotinamide Example 72 Synthesis of (S)-N-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethyl)-3-(1-phenylvinyl)isonicotinamide Compound 122a. To a solution of methyl 3-bromoisonicotinate (1.0 g, 4.6 mmol, 1.0 equiv) in toluene (10 mL) was added 4,4,5,5-tetramethyl-2-(1-phenylvinyl)-1,3,2-dioxaborolane (1.06 g, 4.6 mmol, 1.0 equiv), K3O4P (1.96 g, 9.2 mmol, 2.0 equiv) followed by the addition of Palladium(II) acetate (0.104 g, 0.46 mmol. 0.1 equiv), and Tricyclohexylphosphine (0.130 g, 0.46 mmol. 0.1 equiv) The resulting reaction mixture was heated at 100° C. for overnight. Product formation was confirmed by LCMS. After completion of reaction, the mixture was diluted with water (200 mL) and extracted with ethyl acetate (150 mL*2). Combined organic extracts were washed with water (20 mL*2), dried over anhydrous Na2SO4 and concentrated. The crude product obtained was purified by flash chromatography (0-20% ethyl acetate in hexane as an eluent) to obtain methyl 3-(1-phenylvinyl)isonicotinate (0.560 g, 50% Yield) as brown semi solid. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96% | With [Cu(OH)(IPr)] In neat (no solvent) at 20℃; for 24h; Inert atmosphere; Schlenk technique; Glovebox; | |
| 86% | With C48H108Cl2Co2N8P6U2 In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Sealed tube; regioselective reaction; | General procedures for the hydroboration of alkynes catalyzed by complex 3 General procedure: In an argon-filled glove box, to a 10 mL vial equipped with a stir bar, the alkyne (0.1 mmol)and HBpin (16.0 μL, 0.11 mmol, 1.1 equiv) were added followed by complex 3 (4.2 mg,0.0025 mmol, 2.5 mol%). Then anhydrous THF (1.5 mL) was added. The vial was sealedwith a rubber septum, removed from the glove box and the reaction was stirred for 24 h atroom temperature. Additional water was added into the reaction mixture, and the mixturewas extracted with EtOAc. The organic layer was concentrated to give the crude product.CH2Br2 (3.5 μL) was added as an internal standard for NMR analysis. The product waspurified by chromatography on silica gel for each substrate. |
| 86% | With C48H108Cl2Co2N8P6U2 In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Sealed tube; regioselective reaction; | General procedures for the hydroboration of alkynes catalyzed by complex 3 General procedure: In an argon-filled glove box, to a 10 mL vial equipped with a stir bar, the alkyne (0.1 mmol)and HBpin (16.0 μL, 0.11 mmol, 1.1 equiv) were added followed by complex 3 (4.2 mg,0.0025 mmol, 2.5 mol%). Then anhydrous THF (1.5 mL) was added. The vial was sealedwith a rubber septum, removed from the glove box and the reaction was stirred for 24 h atroom temperature. Additional water was added into the reaction mixture, and the mixturewas extracted with EtOAc. The organic layer was concentrated to give the crude product.CH2Br2 (3.5 μL) was added as an internal standard for NMR analysis. The product waspurified by chromatography on silica gel for each substrate. 4,4,5,5-Tetramethyl-2-(1-phenylvinyl)-1,3,2-dioxaborolane (7a) Prepared according to the general procedure using 4.2 mg (0.0025 mmol)of complex 3, 16.0 μL (0.882 g/mL, 0.11 mmol) of HBpin, 11.0 μL (0.93 g/mL,0.1 mmol) of phenylacetylene (6a) and 1.5 mL of THF. The crude mixturewas purified by flash column chromatography (PE/EtOAc 50/1 as the eluent)to give 7a (18.5 mg, 86% yield) as a yellow oil. 1H NMR (CDCl3, 500 MHz): δ 7.52-7.50 (m,2H), 7.36-7.33 (m, 2H), 7.28-7.25 (m, 1H), 6.11-6.08 (m, 2H), 1,35 (s, 12H); 11B{1H} NMR(CDCl3, 160 MHz): δ 30.7(s); 13C{1H} NMR (CDCl3, 127 MHz): δ 141.4, 130.9, 128.2, 127.2,127.0, 83.8, 24.8 (Carbon attached to boron not observed due to quadrupolar relaxation).The NMR spectra were consistent with the spectra reported in the literature.4 |
| 72% | With potassium acetate; C27H25BrCoF3N3O2 In di-isopropyl ether at 40℃; for 36h; Inert atmosphere; Glovebox; Sealed tube; | |
| 60% | Stage #1: phenylacetylene With Ni(tmhd)2; (1,2-dimethoxyethane)dichloronickel(II); 4'-([1,1'-biphenyl]-4-yl)-2,2':6',2''-terpyridine In tetrahydrofuran at 20℃; for 0.0166667h; Inert atmosphere; Glovebox; Stage #2: pinacolborane In tetrahydrofuran at 60℃; for 2h; Inert atmosphere; Sealed tube; | 3 Example 3: Synthesis of 4,4,5,5-tetramethyl-2-(1-phenylvinyl)-1,3,2-dioxaborolane In a glass vial 4 mL under nitrogen gas, Ni(dpm)2 (8.5 mg, 5.0 mol%)), 4'-([1,'1-biphenyl]-4-yl)-2,2':6',2''-terpyridine (L1, 14 mg, 9.0 mol%), NiCl2dme (0.9 mg, 1.0 mol%), anhydrous THF (2.0 mL, 0.20 M), and phenylacetylene, (60 mg, 0.60 mmol, 1.5 equiv) was added, and the reaction mixture was stirred at room temperature for 1 min. Then, HBpin (59 μL, 0.40 mmol, 1.0 equiv) was added to the vial. After sealing, the vial was taken out of the glove box and stirred at 60 °C for 2 h. The mixture was purified by flash column chromatography on silica (hexane:EtOAc = 50:1) to give the title compound as a pale yellow oil (55 mg, 60%). |
