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( E )‐,( Z )‐Stereodefined α‐Chloro‐β‐tosyloxy‐α,β‐unsaturated Esters: Sequential Cross‐Couplings for ( E )‐,( Z )‐Stereo Complementary Synthesis of Fully‐Substituted α,β‐Unsaturated Esters
Author(s) -
Ashida Yuichiro,
Nakata Kohei,
Yoshitake Daisuke,
Sato Yuka,
Miyazaki Yukie,
Tanabe Yoo
Publication year - 2020
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.202000012
Subject(s) - chemistry , yield (engineering) , aryl , catalysis , enol , medicinal chemistry , reagent , organic chemistry , stereochemistry , alkyl , materials science , metallurgy
Abstract An ( E )‐, ( Z )‐stereocomplementary synthesis of fully‐substituted α,β‐unsaturated esters has been developed. The present method involves sequential cross‐coupling reactions of readily available ( E )‐, ( Z )‐stereodefined α‐chloro‐β‐tosyloxy‐α,β‐unsaturated esters, which were obtained by ( Z )‐ and ( E )‐stereocomplementary enol tosylation of methyl α‐chloro‐β‐oxoesters using novel reagents, TsCl−NaH−TMEDA(−LiCl) for Z and TsCl− i Pr 2 NEt− N ‐methylimidazole for E . The first highly chemoselective and stereoretentive Suzuki‐Miyaura cross‐couplings proceeded smoothly at the β‐TsO‐position of ( E )‐ and ( Z )‐α‐chloro‐β‐tosyloxy‐α,β‐unsaturated esters to afford ( Z )‐ and ( E )‐β‐aryl(Ar)‐α‐chloroacrylates, respectively by an accessible [Pd(OAc) 2 −PPh 3 −K 2 CO 3 ] catalysis (4 examples: 89–94% yield). Subsequent highly stereoretentive Suzuki‐Miyaura cross‐couplings using the obtained ( Z )‐ and ( E )‐acrylates were successfully performed by a reactive [Pd(OAc) 2 −SPhos−K 2 CO 3 ] catalysis to produce a number of ( E )‐ and ( Z )‐ β‐aryl(Ar)‐α‐aryl’(Ar 1 ) and β‐aryl(Ar)‐α‐ n ‐hexyl acrylates (24 examples, 62–94 %). As a distinct extension, ( Z )‐ and ( E )‐β‐( p ‐tolyl)‐α‐chloroacrylate served as appropriate partners for ( E )‐ and ( Z )‐stereoretentive Sonogashira, Mizoroki‐Heck, and Buchwald‐Hartwig cross‐couplings, which afforded the corresponding enyne, diene, and α‐aminoolefin types of fully‐substituted α,β‐unsaturated esters (6 examples: 52–75% yield).