An efficient direct phosphinylation and alkylation of ketones to construct C–P and C–C bonds: access to α,α-disubstituted γ-ketophosphine oxides†

Abstract

The first example of an acid-promoted difunctionalization of ketones to construct C–P and C–C bonds via a phospha-aldol-elimination is described under metal- and solvent-free conditions. The cascade α-phosphorylation and α-alkylation sequence directly converts ketones to α,α-disubstituted γ-ketone phosphine oxides, thereby providing a new strategy for the synthesis of the α,α-disubstituted γ-ketone phosphine oxide anticholinesterase skeleton in moderate to excellent yields with water as the only by-product. Detailed mechanistic experiments verified that the reaction proceeds via a TfOH-induced carbocationic intermediate formed after the α-phosphorylation of ketones.