Ring-contraction strategy for the practical, scalable, catalytic asymmetric synthesis of versatile γ-quaternary acylcyclopentenes.

A simple protocol for the practical, scalable, catalytic asymmetric synthesis of γ-quaternary acylcyclopentenes in up to 91% overall yield and 92% ee has been developed. The reaction sequence employs a palladium-catalyzed enantioselective alkylation reaction and exploits the unusual stability of β-hydroxy cycloheptanones to achieve a general and robust method for performing two-carbon ring contractions. The resulting enantioenriched, highly-functionalized acylcyclopentenes provide a variable substituent and four additional functional group handles for chemoselective manipulation and potential application to the total synthesis of a wide array of natural products.