Enantioselective Reduction of Prochiral Ketones with NaBH₄/Me₂SO₄/(S)-Me-CBS

Abstract

The enantioselective reduction of prochiral ketones with NaBH₄/Me₂SO₄/(S)-Me-CBS is described. Borane is generated in situ via the reaction of NaBH₄ with Me₂SO₄ in tetrahydrofuran, which is as efficient as the commercial one. Such in situ–generated borane reagent was applied to reduce prochiral ketones in the presence of chiral oxazaborolidine catalyst directly. The corresponding chiral secondary alcohols were obtained with excellent enantiomeric excesses (93–99% ee) and good to excellent yield (80–99%).

GRAPHICAL ABSTRACT

Keywords:

• Asymmetric reduction
• chiral alcohols
• chiral oxazaborolidine
• dimethyl sulfate
• sodium borohydride

Notes

^a Reaction conditions: NaBH₄/Me₂SO₄/ketone = 0.7/0.7/1.

^b Isolated yield.

^c Determined by HPLC with a chiral column (Daicel OD).

^d NaBH₄/Me₂SO₄/ketone = 0.6/0.6/1.