Novel Chiral Diamines and (S)-6-Chloronicotine Derivatives as Catalysts for Asymmetric Synthesis

Abstract

Many enantiomerically pure products with biological activities are commonly used in the pharmaceutical industry due to their effectiveness. As such, procedures that produce stereochemically pure compounds are highly desirable. Asymmetric synthesis using chiral compounds has become the preferred way to make enantiopure material. For example, selectively synthesizing secondary alcohols that are ubiquitous in natural products and pharmaceuticals can be achieved through the catalytic asymmetric addition of an alkylzinc to an aldehyde. In the Comins group, we have developed new chiral diamines, amino alcohols, and amino phosphines to test in asymmetric reactions, such as the catalytic addition of diethylzinc to benzaldehyde, and palladium-catalyzed allylic alkylation. Each of these catalysts has a nitrogen containing heterocycle and is synthesized in a few steps from commercially available materials, such as ephedrine and (S)-nicotine. Overall, the amino alcohol derivatives provided the best results in the catalytic asymmetric addition of diethylzinc to various aldehydes, while the amino phosphines showed promise in the palladium-catalyzed allylic alkylation of racemic 1,3-diphenylpropen-2-yl acetate with dimethyl malonate. However, these nicotine–based catalysts did not show great selectivity or usefulness in other metal–catalyzed reactions, such as zinc alkynylations to aldehydes, copper–catalyzed 1,4–additions, the Henry reaction, and allylic oxidations.