Open AccessDivergent Synthetic Access to E ‐ and Z ‐Stereodefined All‐Carbon‐Substituted Olefin Scaffolds: Application to Parallel Synthesis of ( E )‐ and ( Z )‐Tamoxifens
Author(s) -
Ashida Yuichiro,
Honda Atsushi,
Sato Yuka,
Nakatsuji Hidefumi,
Tanabe Yoo
Publication year - 2017
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.201600124
Subject(s) - chemistry , yield (engineering) , olefin fiber , negishi coupling , reagent , derivatization , carbon fibers , base (topology) , medicinal chemistry , catalysis , stereochemistry , combinatorial chemistry , organic chemistry , mathematics , materials science , high performance liquid chromatography , algorithm , mathematical analysis , composite number , metallurgy
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.