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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.

The key transformation is the palladium-catalyzed asymmetric decarboxylative alkylation of seven-membered β-ketoesters (I) to form quaternary vinylogous esters (II).

Enantioselective decarboxylative internal allylation of esters (I) followed by hydride reduction and base-promoted ring contraction of the intermediate cyclic β-hydroxy ketones affords densely functionalized chiral acylcyclopentenes.

Formation and growth of the title nanocrystals in high-temperature, high-pressure aqueous KOH solutions of Fe(NO3)3 and Bi(NO3)3 is monitored by in situ synchrotron powder XRD.