Divergent Synthetic Access to E‐ and Z‐Stereodefined All‐Carbon‐Substituted Olefin Scaffolds: Application to Parallel Synthesis of (E)‐ and (Z)‐Tamoxifens

A highly substrate‐general synthesis of all‐carbon‐substituted E‐ and Z‐stereodefined olefins is performed. The method comprises two sets of parallel and stereocomplementary preparations of (E)‐ and (Z)‐α,β‐unsaturated esters involving two robust and distinctive reactions: 1) stereocomplementary enol tosylations using readily available TsCl/diamine/(LiCl) base reagents, and 2) stereoretentive Negishi cross‐coupling using the catalysts [Pd(dppe)Cl(2)] (for E) and [Pd(dppb)Cl(2)] (for Z). The present parallel approach is categorized as both type I (convergent approach: 16 examples, 56–87 % yield) and type II (divergent approach: 18 examples, 70–95 % yield). The obtained (E)‐ and (Z)‐α,β‐unsaturated ester scaffolds are successfully transformed into various E‐ and Z‐stereodefined known and novel olefins (8×2 derivatization arrays). As a demonstration, application to the parallel synthesis of both (E)‐ and (Z)‐tamoxifens, a representative motif of all‐carbon‐substituted olefins, is accomplished in a total of eight steps with an overall yield of 58 % (average 93 %) and 57 % (average 93 %), respectively.