Lithium tri-s-butylborohydride → (S)-N-((R)-4-(3,4-dichlorophenyl)butan-2-yl)-2-methylpropane-2-sulfinamide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (S)-2-methylpropane-2-sulfinamide (373 mg, 3.08 mmol) and 4-(3,4-dichlorophenyl)butan-2-one (700 mg, 3.22 mmol) in THF (2 mL) at rt was added tetraethoxytitanium (1.22 mL, 5.86 mmol). The reaction mixture was heated at 75° C. overnight, and allowed to cool and stay at rt for 72 h. Another equivalent of Ti(OEt)4 (1.22 mL, 5.86 mmol) and (S)-2-methylpropane-2-sulfinamide (373 mg, 3.08 mmol) were added. The reaction mixture was heated at 75° C. overnight. The THF solution of (S,E)-N-(4-(3,4-dichlorophenyl)butan-2-ylidene)-2-methylpropane-2-sulfinamide (1033 mg, 3.23 mmol) was stirred in a round-bottomed flask under argon at −40 to −50° C. L-Selectride (2016 μL, 2.016 mmol) was added dropwise. The resulting mixture was then warmed up to 0° C. during a 1.5 h period and LC-MS showed the completion of the reaction. It was cooled in dry ice and MeOH was added dropwise until gas evolution stopped. The mixture was stirred at rt for 20 min. It was filtered through Celite® and rinsed with CH2Cl2 and the filtrate was washed with brine (2×) and dried over Na2SO4, filtered and concentrated. The residue was purified on ISCO flash chromatography (0-100% hexanes/EtOAc) to give (S)-N-((R)-4-(3,4-dichlorophenyl)butan-2-yl)-2-methylpropane-2-sulfinamide (620 mg, 1.924 mmol, 59.6% yield) as slightly tan viscous oil (slow eluent) and an impure (S)-N-((S)-4-(3,4-dichlorophenyl)butan-2-yl)-2-methylpropane-2-sulfinamide. LC-MS (ESI) m/z 322.0 (M+H), RT=2.34 min (Method B).

Provenance & Evidence