Formic Acid → (4R)-4-[(1S)-1-hydroxyethyl]-1-[(1R)-1-(4-methoxyphenyl)ethyl]pyrrolidin-2-one

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Reaction Steps

In a vial under N2, [Rh(C5Me5)Cl2]2 (62 mg, 0.10 mmol) and (1R,2R)-(−)-N-p-Tosyl-1,2-diphenylethylenediamine (87 mg, 0.24 mmol) were taken up in MeCN (1 mL). Triethylamine (0.1 mL, 0.7 mmol) was added and the resulting mixture was stirred 40 min prior to use. Meanwhile, a solution of (R)-4-acetyl-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.03 (1.06 g, 4.06 mmol) and triethylamine (3 mL, 21.3 mmol) in MeCN (20 mL) was cooled to an internal temperature of −10° C. under Ar in a jacketed 3-neck flask equipped with a thermocouple. Formic acid (0.525 mL, 13.9 mmol) was added during the cooling ramp once the internal temperature reached 0° C. Once the internal temperature reached −10° C., the aforementioned catalyst mixture was added in one portion, washing with additional MeCN (3×1 mL). The resulting orange solution was stirred for 48 h at −10° C. and was then warmed to r.t. Hydrochloric acid (3 M, 7.5 mL, 22.5 mmol) was added followed by dilution with EtOAc (50 mL) and brine (30 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (50 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated onto 10 g silica gel. The product was purified by silica gel chromatography (35% to 50% acetone in hexanes) to afford (R)-4-((S)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.05.

Provenance & Evidence