Phosphine-Free Pincer Ruthenium-Catalyzed α-Alkylation of Ketones with Secondary Alcohols to form β-Branched Ketones

Herein, an efficient and expedient method was developed for alpha-alkylation of aromatic ketones with secondary alcohols to produce beta-disubstituted ketones using phosphine-free pincer ruthenium complexes as the catalyst. Single alpha-alkylated ketone is produced in high yields even in reactions where a mixture of products is possible. Interestingly, challenging substrates such as unsubstituted and nonhindered acetophenone compounds are effectively alkylated under the reaction conditions. The scope of the reaction can span with a verities of aliphatic, cyclic, and acyclic secondary alcohols. Functionalization of a cholesterol molecule is also possible under the reaction conditions. Substitution on cyclohexyl ring afforded products as a mixture of diastereoisomers, wherein the major isomer is found as 1,4-cis conformation of the cyclohexyl ring. Origin of the cis stereoselectivity in the alkylation process was explored by DFT calculation study. Mechanistic studies reveal that the dehydrogenation of alcohols follows a proton shuttle-type of TS, involvement of cross-aldol condensation and borrowing hydrogen catalysis. Notably, this selective, catalytic C-C bond forming reaction proceeds with low catalyst load, catalytic amount of base under air and produces H2O as the only byproduct, making the process environmentally benign and atom efficient.