Wacker Oxidation of Methylenecyclobutanes: Scope and Selectivity in an Unusual Setting

Methylenecyclobutanes undergo Wacker oxidation towards cyclopentanones under mild reaction conditions. A semi-pinacol-type rearrangement is proposed to be responsible for the intermediary 1,2-shift, which not only explains the formation of the products, but also rationalizes the reaction outcomes in terms of site-, regio- and enantioselectivity.

Abstract

Methylenecyclobutanes are found to undergo Wacker oxidation via a semi-pinacol-type rearrangement. Key to a successful process is the use of tert-butyl nitrite as oxidant, which not only enables efficient catalyst turn-over but also ensures high Markovnikov-selectivity under mild conditions. Thus, cyclopentanones (26 examples) can be accessed in an overall good yield and excellent selectivity (up to 97 % yield, generally >99 : 1 ketone:aldehyde ratio). Stereochemical analysis of the reaction sequence reveals migration aptitudes in line with related 1,2-shifts. By introducing a pyox ligand to palladium, prochiral methylenecyclobutanes can be desymmetrized, thus realizing the first enantioselective Wacker oxidation.

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