Catalytic, Enantioselective Vinylogous Mukaiyama Aldol Reaction of Furan-Based Dienoxy Silanes: A Chemodivergent Approach to γ-Valerolactone Flavan-3-ol Metabolites and δ-Lactone Analogues

The asymmetric synthesis of a set of hydroxyphenyl gamma-valerolactones was achieved starting from 2-silyloxyfuran and alkoxy-substituted benzaldehydes as common precursors. Key synthesis steps included an enantioselective vinylogous Mukaiyama aldol reaction and a Barton-McCombie deoxygenation. Five enantioenriched gamma-valerolactone targets were obtained in 5-6 steps, 18-63% overall yields and 82-98% ee, paving the way for the straightforward entry to this class of biologically effective and poorly available flavan-3-ol metabolites. In parallel, an unprecedented one-pot reductive ring expansion process was fortuitously discovered, yielding racemic delta-lactone analogues from phenolic butanolide precursors.