Investigation of α‐Silylalcohols as Chiral Umpolung Carbanion Surrogates Through Stereospecific 1,2‐Brook Rearrangement

We report the investigation of the enantiospecific trapping of chiral α‐silyl secondary alcohols through stereospecific 1,2‐Brook rearrangement of the lithium alkoxide. The reaction proceeds through a chiral polarity‐reversed carbanion intermediate that can be trapped faster than racemization in many cases. Weinreb amides were applied as electrophiles to access enantioenriched α‐hydroxyketones in good yields and variable enantiopurities. Substituent effect studies showed that product enantiopurity was a function of the rate of electrophilic trapping of the intermediate chiral carbanion, with faster trapping rates affording higher chirality transfer. The chiral α‐silyl secondary alcohols were conveniently accessed in high enantiopurity using Noyori asymmetric transfer hydrogenation (ATH) with low catalyst loading (0.5 mol% Ru).