The asymmetric α-alkylation of carbonyl compounds is a fundamental synthetic transformation. Remarkably, despite its importance, there is no general way to conduct this transformation in a catalytic asymmetric fashion. The umpolung-based alkylation of ketones and aldehydes, wherein an organometallic species adds to an electrophilic α-carbon through the intermediacy of a derived azo- or nitrosoalkene, provides an appealing approach to effecting this transformation. Not only does such an approach allow for the incorporation of functionality that cannot be introduced using enolate chemistry, but it is also well suited to catalysis and adaptable for asymmetric induction. Given the wide range of structures available as organometallic reagents (e.g., 1˚, 2˚, 3˚ alkyl, aryl, vinyl, alkynyl, etc.), this approach to catalytic asymmetric α-alkylation is also likely to prove broad in scope. Herein, we describe our recent efforts to exploit this mode of reactivity to provide a solution to the long-standing problem of developing a general, catalytic asymmetric approach to the α-alkylation of carbonyl compounds.

Umpolung approach to the asymmetric α-alkylation of aldehydes and ketones

249th National Meeting (2015)

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