Effect of borane source on the enantioselectivity in the enantiopure oxazaborolidine‐catalyzed asymmetric borane reduction of ketones

Obtaining Enriched Compounds via a Tandem Enantioselective Reaction and Kinetic Resolution Polishing Sequence

“…In order to demonstrate the utility of this process, a prochiral ketone was reduced by the Corey–Bakshi–Shibata catalyst ( S )-MeCBS to produce an enantioenriched alcohol with moderate ee . While ( S )-MeCBS can reduce ketones to their corresponding alcohols in ee’s greater than 99%, the reaction is sensitive to slight changes in the reaction conditions . This is demonstrated from our results in Scheme where acetophenone is reduced to the enantioenriched ( R )-phenylethanol ( 1­( R ) ) by the ( S )-MeCBS catalyst.…”

“…The challenge with performing these reactions in one-pot is that the product of the enantioselective reduction is a boronate salt that will not undergo acylation (Table , entry 1). Since the addition of methanol is a common workup strategy for the CBS enantioselective reduction, methanol was added as a coupling reagent to free the alcohol 1­( R ) for the kinetic resolution. Theoretically, only 3 equiv of methanol should be required to cleave off the boron and free the alcohol for the acylation.…”