Nat Chem. 2017 Feb;9(2):179-187. doi: 10.1038/nchem.2638. Epub 2016 Nov 14.

By-design enantioselective self-amplification based on non-covalent product-catalyst interactions.

Nature chemistry

Golo Storch, Oliver Trapp

PMID: 28282051 DOI: 10.1038/nchem.2638

Abstract

The synthesis of enantiomerically pure compounds is of great importance in pharmaceuticals, fragrances and biological applications, and functions as a key to many processes in nature. Asymmetric catalysis using enantiomerically pure catalysts represents an efficient synthetic method to achieve this goal. The enantiomeric excess of the reaction product correlates with the enantiomeric purity of the catalysts, except for nonlinear behaviour, therefore the use of stereochemically flexible catalysts seems to complicate the control of stereoselectivity. Self-amplifying catalytic reactions are attractive, but a general rational design is highly challenging. Here we show that product interaction with chiral recognition sites attached to structurally flexible phoshoramidite-type catalysts can sense the chirality and induce enantioselectivity in the catalyst. Structural flexibility along with sensing of the chirality of the product molecules results in a rapid increase of enantioselectivity of the dynamic catalysts (Δe.e. of up to 76%) and a shift out of equilibrium. In contrast to stereodynamic catalysts controlled with cleavable chiral auxiliaries, the enantioselectivity does not decrease.

Publication Types

• Journal Article
• Research Support, Non-U.S. Gov't

Grant support

• 258740/European Research Council/International