One-Pot, Modular Approach to Functionalized Ketones via Nucleophilic Addition of Alkyllithium Reagents to Benzamides and Pd-Catalyzed α-Arylation

Article abstract of DOI:10.1021/acscatal.6b00134

An efficient, in situ sequential 1,2-addition of alkyllithium reagents to benzamides followed by α-arylation of the resulting alkyl ketones is reported. The use of Pd[P(t-Bu)₃]₂, as catalyst for the α-arylation reaction, allows access to a wide variety of functionalized benzyl ketones in a modular way. The decomposition of the tetrahedral intermediate originated from the 1,2-addition liberates in situ a lithium amide, therefore avoiding the need of an external base for the α-arylation. The method affords good overall yields with a variety of alkyl lithium reagents, benzamides, and aryl bromides, bearing a range of functional groups with complete selectivity toward the monoarylated products.