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

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• 作者：Yuichiro Ashida ; Atsushi Honda ; Yuka Sato ; Dr. Hidefumi Nakatsuji and Prof. Dr. Yoo Tanabe
• 刊名：ChemistryOpen
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：6
• 期：1
• 页码：73-89
• 全文大小：1728K
• ISSN：2191-1363

文摘

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)Cl₂] (for E) and [Pd(dppb)Cl₂] (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.