Concise enantioselective synthesis of δ,δ-disubstituted δ-valerolactones

Abstract

Efficient access to enantioenriched δ,δ-disubstituted δ-valerolactones is described. A soft Lewis acid/hard Brønsted base cooperative catalyst allowed for direct catalytic asymmetric γ-addition of allyl cyanide to ketones, producing tertiary homoallylic alcohols with a Z-configured α,β-unsaturated nitrile. Electrophilic activation of the nitrile functionality triggered 6-exo-dig cyclization, and subsequent N-acylation gave rise to the δ-valerolactone skeleton via CN bond cleavage.