Chlorotrimethylsilane → HCID 89499943, compound

Participants

Reaction Steps

Cp2ZrHCl (206 mg, 0.80 mmol, 2.0 eq.) was added to a stirred, room temperature, solution of 5-bromo-1-pentene (0.12 mL, 1.0 mmol, 2.5 eq.) in CH2Cl2 (0.40 mL) under an argon atmosphere. After stirring for about 15 min, the resulting clear yellow solution was transferred via syringe over about 1 min to a clear colourless stirred solution of CuOTf-ligand complex (30.0 mg, 0.040 mmol, 0.10 eq.) in Et2O (2.0 mL) under an argon atmosphere. The resulting dark mixture was allowed to stir for an additional 10 min before 1,4-androstadiene-3,17-dione (114.0 mg, 0.40 mmol, 1.0 eq.) and TMSCl (0.26 mL, 2.00 mmol, 5.0 eq.) were added sequentially dropwise via syringe. Stirring at room temperature was continued arbitrarily for 15 h before the reaction was quenched by the addition of Et2O (ca 3 mL) and NH4Cl (1 M aq., ca 1.5 mL). The mixture was partitioned between the aqueous and Et2O layers and the former phase was extracted with Et2O (3×10 mL). The combined organic phase was washed with NaHCO3 (sat. aq., ca 10 mL), dried (Na2SO4), filtered and concentrated in vacuo to give an oil. Flash column chromatography of the yellow residue (10:30:60 EtOAc/DCM/petrol; SiO2) gave major diastereomer (3) (+)-1α-(5-Bromopentyl)-4-androstene-3,17-dione (107 mg, 0.24 mmol, 60%) and minor diastereomer (3a) (+)-1α-(5-Bromopentyl)-4-androstene-3,17-dione (14 mg, 0.032 mmol, 8%). Diastereomeric ratio (4.8:1) was determined by integration of 1H NMR spectra.

Provenance & Evidence