Tin-free Radical Allylation of α-Acetoxy Alkyl Xanthates. Routes to Homoallyl Alcohols and α,β-Unsaturated Ketones

Abstract

Radical allylations are most frequently used intermolecular radical carbon-carbon bond forming reactions and provide an easy access to introduce allyl groups into organic molecules under mild conditions. Allylating agents normally utilize simple allyl and 2-substituted allyl stannanes along with the corresponding sulfides and sulfones. Contrary to the radical allylations, radical-mediated aldol reactions have not been well developed due to the very high π-bond strength of C=O bonds. Thus, several indirect approaches for aldol-type products have been reported to date. We studied the possibility of indirect radicalmediated aldol reactions using α-acetoxy alkyl radicals along with reagent equivalents of the α-ketone acceptor synthon. In this regard, 2-acetoxy and 2-benzoyloxy substituted allyl sulfones seemed to be promising for our purpose. The combination of these new allylating agents together with the α-acetoxy alkyl radical precursors would provide α,β-unsaturated ketones after hydrolysis of the acetates and the following dehydration. Among several α-alkoxy alkyl radical precursors, αbromoalkyl acetate 1 seemed to be most attractive and promising to introduce an acetate group at the β-position of an alkenyl bond. Previously, radical allylation of 1 with allyl stannane was known to give a homoallyl acetate. Furthermore, chiral α-alkoxy alkyl radicals were generated from decarboxylation of α-alkoxy substituted Barton esters. The α-bromoalkyl acetate 1 was readily prepared by the addition of acetyl bromide to an aldehyde in the presence of zinc chloride in methylene chloride at 0 C (eq. 1).