Stereoselective protonation of 2-methyl-1-tetralone lithium enolate catalyzed by salan-type diamines

Asymmetric protonation of ketone enolates is a convenient alternative to asymmetric alkylation of enolates that allows to convert racemic ketones into their optically active form. Here, we have reported an efficient enantioselective protonation of 2-methyl-1-tetralone lithium enolate catalyzed by salan-type diamines. A broad series of salan-type catalysts were synthesized, including several previously unknown, and subsequently tested in the title reaction. For the first time, a chiral amine used as organocatalyst has shown better results than as stoichiometric protonating agent. Application of only 10 mol% of salan allows to obtain the title ketone with high yield and enantiomeric excess up to 75%. The DFT calculations of the structure of the catalyst and its complex with lithium enolate were conducted, which makes it possible to propose a likely reaction mechanism. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

An efficient enantioselective protonation of 2-methyl-1-tetralone lithium enolate catalyzed by salan-type diamines is reported in this study. A broad series of salan-type catalysts were synthesized and tested in the reaction, with a chiral amine organocatalyst showing better results than a stoichiometric protonating agent for the first time. The use of only 10 mol% of salan allows for high yield and enantiomeric excess up to 75% in obtaining the title ketone.