Method for Catalytic Enantioselective Alkylation of Aldehydes Using Grignard Reagents as Alkyl Sources

Abstract

Alkyltitanium reagents, generated in situ from Grignard reagents and ClTi(O Pr), can be employed without further manipulation in the enantioselective alkylation of aldehyde by the catalysis of a chiral titanium complex derived from DTBP-H-BINOL. The reaction is performed with good stoichiometry [1.5 equiv each of Grignard reagents and ClTi(O Pr)] at a low catalyst loading (2 mol %), affording a variety of chiral secondary alcohols in high enantioselectivity and yields and, hence, realizing an asymmetric version of the Grignard reaction in an indirect manner.

Recent developments in enantioselective titanium-catalyzed transformations

“…One drawback of these processes is the required removal of coproduced magnesium salts through centrifugation before adding the aldehyde partner to the reaction mixture. In 2018, Harada et al showed that it was possible to avoid this manipulation by generating the reactive alkyltitanium species from TiCl(Oi-Pr)3 instead of Ti(Oi-Pr)4 [12]. Indeed, R 2 MgX was treated with TiCl(Oi-Pr)3 (1.5 or 2 equiv) to give a mixture of R 2 Ti(Oi-Pr)3 and MgXCl.…”

“…( Scheme 3. Alkylation of aldehydes with Grignard reagents in the presence of H8-BINOLderived ligand 5 [12].…”