α‐Arylation of Cyclopentanones by Palladium/Enamine Cooperative Catalysis

Abstract

This chapter presents the procedure for α‐arylation of cyclopentanones by palladium/enamine cooperative catalysis. The procedures in Organic Syntheses are intended for use only by persons with proper training in experimental organic chemistry. Among various ketone functionalization strategies, the Buchwald–Hartwig–Miura (BHM) arylation has been a widely used approach for α‐arylation of ketones via transition metal‐catalyzed cross‐couplings with aryl halides. However, simple or less substituted cyclopentanones have been very difficult substrates for the BHM reaction, attributed to the side reaction of cyclopentanones under strong basic conditions. To address the challenge of α‐arylation of cyclopentanones, a new strategy based on the palladium/enamine cooperative catalysis was developed in 2016. Good site‐selectivity was observed with the α‐substituted cyclopentanones, favoring arylation at the less sterically hindered side. Therefore, this reaction could represent a general method for mono‐α‐arylation of cyclopentanones.