Regioselective Hydrosilylation of Propargylic Alcohols: An Aldol Surrogate

摘要

The aldol reaction has emerged as one of the most powerful ways to assemble complex targets with high stereochemical control in both a relative and an absolute sense. Despite the tremendous successes, deficiencies exist. As aldol adducts are prone to further reactions such as elimination, further substitution at the α-carbon becomes difficult. Asymmetric additions of methyl alkyl ketones have been very limited. Propargylic alcohols can become surrogates for aldols provided that a chemo- and regioselective introduction of a carbonyl group at the alkyne carbon β to the alcohol can be performed. The asymmetric access to propargylic alcohols makes this approach an attractive alternative to the asymmetric aldol reaction. Although the direct hydration of a propargylic alcohol is a potentially attractive solution, the difficulty of obtaining regioselectivity as well as of avoiding elimination of the hydroxy ketone product under generally acidic hydration conditions led us to another approach. As outlined in Equation 1, we chose to pursue selective incorporation of a vinyl C-Si bond, which can serve as a versatile ketone precursor.