Stereoselective Construction of Fluorinated Quaternary Stereogenic Centers via an Organocatalytic Asymmetric exo-Selective Diels-Alder Reaction in the Presence of Water

Org Lett. 2022 Oct 14;24(40):7455-7460. doi: 10.1021/acs.orglett.2c03043. Epub 2022 Oct 3.

Abstract

A catalytic, asymmetric Diels-Alder reaction of α-fluoro α,β-unsaturated aldehydes and cyclopentadiene was developed using diarylprolinol silyl ether as an organocatalyst. The reaction proceeds in toluene with trifluoroacetic acid as an additive (condition A). Perchloric acid salt of diarylprolinol silyl ether also promotes the reaction using water as a reaction medium (condition B). In both cases, excellent exo-selectivity and enantioselectivity were obtained with generation of a fluorinated quaternary chiral center.