Phenylacetylene → (+/-)-(4R*,5R*)-5-((1R*)-1-hydroxy-3-phenylprop-2-ynyl)-1-methyl-4-phenyl-pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a −20° C. solution of phenylacetylene (0.29 mL, 2.69 mmol) in anhyd. THF (1 mL) was added a solution of n-BuLi (1.6M in hexane, 1.56 mL, 2.50 mmol). The reaction mixture was stirred for 2 h at −20° C., then was cooled to −78° C. A solution of (±)-(4R*,5R*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one (Intermediate Z, 389 mg, 1.92 mmol) in THF (2 mL) was added dropwise. The reaction mixture was allowed to warm to room temperature, stirred for 18 h, then treated with a saturated NH4Cl solution and extracted with CH2Cl2. The combined organic layers were washed with a saturated NaCl solution, dried (Na2SO4) and concentrated under reduced pressure. The crude product was purified by flash chromatography (90% EtOAc/hex) to give (±)-(4R*,5R*)-5-((1R*)-1-hydroxy-3-phenylprop-2-ynyl)-1-methyl-4-phenyl-pyrrolidin-2-one (230 mg, 40%) as a white solid: mp 152-153° C.; 1H NMR (CDCl3) δ 2.78-3.09 (m, 5H), 4.02 (q, J=9.0 Hz, 1H), 4.38 (dd, J=9.0 Hz, 2.0 Hz, 1H), 7.22-7.40 (m, 10H), 9.18 (d,J=2.0 Hz, 1H).

Provenance & Evidence