Structure of 83947-56-2
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Gruszczyński, Marcin ; Lewandowski, Dariusz ; Kuciński, Krzysztof ; Kubicki, Maciej ; Hreczycho, Grzegorz ;
Abstract: Nickel catalysis provides opportunities to modulate reaction pathways through changes in the coordination environment, yet strategies to deliberately redirect nickel reactivity remain limited. Here we show that ligand exchange at nickel allows a single catalytic system to produce different products from the same alkyne substrates. Aminophosphine-supported nickel catalysts promote selective hydroboration in the presence of pinacolborane, which functions both as a boron source and a reaction activator. The addition of TEMPO forms a distinct ligand-coordinated nickel species that suppresses hydroboration and directs the reaction toward enyne formation. Our further studies identify TEMPO coordination as a key step that directs the catalytic cycle, illustrating how simple additives can influence reaction outcomes. These results offer a straightforward strategy to access divergent reactivity in nickel catalysis and provide insight into the factors controlling catalytic pathway selection.
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Keywords: Alkynes ; Nickel catalysis ; Ligand effects ; Hydroboration ; Enynes
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| CAS No. : | 83947-56-2 |
| Formula : | C14H19BO2 |
| M.W : | 230.11 |
| SMILES Code : | CC1(C)C(C)(C)OB(/C=C/C2=CC=CC=C2)O1 |
| English Name : | E-Phenylethenylboronic acid, pinacol ester |
| MDL No. : | MFCD03453666 |
| InChI Key : | ARAINKADEARZLZ-ZHACJKMWSA-N |
| Pubchem ID : | 5708413 |
| 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 |
3.55 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.22 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.19 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.39 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.27 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-3.63 |
| Solubility | 0.0537 mg/ml ; 0.000233 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-3.62 |
| Solubility | 0.0549 mg/ml ; 0.000238 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.09 |
| Solubility | 0.0186 mg/ml ; 0.0000807 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 |
-5.18 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) |
3.0 |
* 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 |
|---|---|---|
| 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 |
|---|---|---|
| 71% | With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; water In tetrahydrofuran at 18℃; for 24h; Inert atmosphere; Sealed tube; chemoselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 69% | With potassium phosphate; palladium diacetate; DavePhos In tetrahydrofuran; water at 90℃; for 16h; chemoselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 48% | With isonicotinate tert-butyl ester at 110℃; for 15h; Schlenk technique; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 73% | With palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate In N,N-dimethyl-formamide at 90℃; for 24h; Inert atmosphere; | General Procedure I: Cross-Coupling Protocol General procedure: To an oven-dried, 25 mL round-bottomed flask, containing a magnetic stir-bar was added Pd(OAc)2 (0.05 equiv), t-Bu3PHBF4 (0.10 equiv), and K2CO3 (1.2 equiv). (E)-2-phenylethenylboronic acid pinacol ester (1.2 equiv) was weighed, dissolved in DMF ([0.2] with respect to the aromatic bromide), and then added to the solid reagents. The flask was capped witha septum, purged with argon for 10 min, and the aromatic bromide (1.0 equiv) was added by syringe. The flask was then placed in a preheated oil bath (90 °C) and allowed to stir under aballoon of argon. The reaction was determined to be complete by TLC and GC-MS analysis of a crude reaction aliquot. The reaction was then cooled to rt, poured into a separatory funnel containing H2O (10 mL), and extracted with EtOAc (3 × 10 mL). The three separate organic extracts were then sequentially washed with H2O (2 × 10 mL) and brine (20 mL). The organic extracts were combined, dried over Na2SO4 until flocculent, and filtered. Concentration of the filtrate and purification by flash chromatography (silica gel) provided the desired product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 76% | With palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate In N,N-dimethyl-formamide at 90℃; for 20h; Inert atmosphere; | General Procedure I: Cross-Coupling Protocol General procedure: To an oven-dried, 25 mL round-bottomed flask, containing a magnetic stir-bar was added Pd(OAc)2 (0.05 equiv), t-Bu3PHBF4 (0.10 equiv), and K2CO3 (1.2 equiv). (E)-2-phenylethenylboronic acid pinacol ester (1.2 equiv) was weighed, dissolved in DMF ([0.2] with respect to the aromatic bromide), and then added to the solid reagents. The flask was capped witha septum, purged with argon for 10 min, and the aromatic bromide (1.0 equiv) was added by syringe. The flask was then placed in a preheated oil bath (90 °C) and allowed to stir under aballoon of argon. The reaction was determined to be complete by TLC and GC-MS analysis of a crude reaction aliquot. The reaction was then cooled to rt, poured into a separatory funnel containing H2O (10 mL), and extracted with EtOAc (3 × 10 mL). The three separate organic extracts were then sequentially washed with H2O (2 × 10 mL) and brine (20 mL). The organic extracts were combined, dried over Na2SO4 until flocculent, and filtered. Concentration of the filtrate and purification by flash chromatography (silica gel) provided the desired product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 67 %Chromat. | With bis(cyclopentadienyl)dihydrozirconium In toluene at 130℃; Inert atmosphere; Glovebox; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 79 %Chromat. | With bis(cyclopentadienyl)dihydrozirconium In toluene at 130℃; Inert atmosphere; Glovebox; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 72 %Chromat. | With bis(cyclopentadienyl)dihydrozirconium In toluene at 130℃; Inert atmosphere; Glovebox; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 20 %Chromat. | With bis(cyclopentadienyl)dihydrozirconium In toluene at 130℃; Inert atmosphere; Glovebox; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 100% | With trans-bis(triphenylphosphine)palladium dichloride; potassium carbonate In 1,4-dioxane; water at 100℃; Inert atmosphere; | S-14.1 Step 1 : Synthesis of (E)-6-styrylquinoline-4-carboxylic acid. To a solution of 6- bromoqumolme-4-carboxyiic acid (0.2 g, 0.8 mmol, 1.0 equiv) and (E)-2-styryl)-4,4,5,5- tetramethyl-l,3,2-dioxaborolane (0.22 g, 0.96 mmol, 1.2 equiv) in dioxane (10 ml) and water (2 ml) was added in K2CO3 (0.169 g, 1 .6 mmol, 2.0 equiv) and the mixture was purged with N2 gas for 10 min, followed by the addition of Pd(PPh2)Ck (0.028 g, 0.04 mmol. 0.05 equiv). The resulting reaction mixture was heated at 100° C for overnight. Product formation was confirmed by LCMS After the completion of reaction the reaction mixture was diluted with water (30 mL) and washed with ethyl acetate (50 mL x 2). Aqueous layer was separated and dried over lyophiiizer to obtain (E)-6-styrylquinoline-4-carboxylic acid (0.300 g, Quant. Yield) as a yellow solid. LCMS 276.0 [M+H]+ |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 78 % | Stage #1: 4,4,5,5-tetramethyl-2-((E)-styryl)-[1,3,2]dioxaborolane With hydrogenchloride; sodium periodate; water In tetrahydrofuran at 20℃; Stage #2: formaldehyd; diphenylmethylpiperazine at 90℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: 1-(tert-butyloxycarbonyl)-5-methoxyindole With n-butyllithium In tetrahydrofuran; pentane at 0 - 20℃; Inert atmosphere; Stage #2: 4,4,5,5-tetramethyl-2-((E)-styryl)-[1,3,2]dioxaborolane In tetrahydrofuran; pentane at -78 - 20℃; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With copper diacetate; sodium hydride In toluene at 110℃; Sealed tube; Molecular sieve; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 2-methyltetrahydrofuran; water at 75℃; Inert atmosphere; | Synthesis of the Compound of the Invention 2,5-Dibromo-4-iodopyridine (15 g, 1 Eq, 41.4 mmol) was dissolved in 2-MeTHF (150 mL), (E)-4,4,5,5-tetramethyl-2-styryl-1,3,2-dioxaborolane (10.6 g, 1.114 Eq, 46.1 mmol), water (100 mL, 1.5 mol, 3.6 Eq, 150 mmol), K3PO4 (1.5 M) and Pd(dppf)Cl2.DCM (1.64 g, 0.05 Eq, 2.1 mmol) were added to the mixture degassed with nitrogen gas, and heated to 75°C for 20 hours. After cooling to room temperature, the reaction mixture was filtered and transferred to a separatory funnel. The organic layer was drained and the aqueous layer was re-extracted with 2-MeTHF (250 mL). The combined organic layers were then dried over anhydrous Mg2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel using 5-20% MTBE/iso-hexane as eluent to give (E)-2,5-dibromo-4-styrylpyridine (12.2 g, 29 mmol, 70%, 80% purity). |

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