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

Abstract Herein, an efficient and expedient method was developed for α‐alkylation of aromatic ketones with secondary alcohols to produce β ‐disubstituted ketones using phosphine‐free pincer ruthenium complexes as the catalyst. Single α ‐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 H 2 O as the only byproduct, making the process environmentally benign and atom efficient.