(E)-,(Z)-parallel preparative methods for stereodefined β,β-diaryl- and α,β-diaryl-α,β-unsaturated esters: application to the stereocomplementary concise synthesis of zimelidine.

Abstract

Parallel and practical methods for the preparation of both (E)- and (Z)-β-aryl(1)-β-aryl(2)-α,β-unsaturated esters 1 and (E)- and (Z)-α-aryl(1)-β-aryl(2)-α,β-unsaturated esters 2 are described. These methods involve accessible, robust, stereocomplementary N-methylimidazole (NMI)-mediated enol tosylations (14 examples, 70-99% yield), as well as stereoretentive Suzuki-Miyaura cross-couplings (36 examples, 64-99% yield). The highlighted feature of the present protocol is the use of parallel and stereocomplementary approaches to obtain highly (E)- and (Z)-pure products 1 and 2 by utilizing sequential enol tosylations and cross-coupling reactions. An expeditious and parallel synthesis of (E)- and (Z)-zimelidine (3), which is a highly representative selective serotonin reuptake inhibitor (SSRI), was performed by utilizing the present methods.