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Stereocomplementary and Parallel Syntheses of Multi‐Substituted ( E )‐, ( Z )‐Stereodefined α,β‐Unsaturated Esters: Application to Drug Syntheses
Author(s) -
Ashida Yuichiro,
Tanabe Yoo
Publication year - 2020
Publication title -
the chemical record
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.61
H-Index - 78
eISSN - 1528-0691
pISSN - 1527-8999
DOI - 10.1002/tcr.202000076
Subject(s) - chemistry , enol , negishi coupling , pharmacophore , sonogashira coupling , combinatorial chemistry , cyclopropane , olefin fiber , mitsunobu reaction , reagent , organic chemistry , stereochemistry , palladium , ring (chemistry) , catalysis
Ubiquitous α,β‐unsaturated esters are well recognized as key structural olefin scaffolds in organic chemistry. ( E )‐ and ( Z )‐steroselectivity is the most critical issue in their synthesis, however, ( E )‐ and ( Z )‐ stereocomplementary synthetic methods remain quite limited. The present account discloses general ( E )‐, ( Z )‐stereocomplementary syntheses of a variety of α,β‐unsaturated esters from highly accessible ( E )‐, ( Z )‐stereodefined enol tosylates derived from β‐ketoesters and α‐formyl esters. Step 1 toward the stereocomplementary preparation of ( E )‐, ( Z )‐stereodefined enol tosylates is implemented by using inexpensive reagents under mild reaction conditions. Step 2 toward the highly stereoretentive synthesis of ( E )‐ and ( Z )‐stereodefined α,β‐unsaturated esters involves Suzuki‐Miyaura, Negishi, Sonogashira, Iron‐catalyzed, Mizoroki‐Heck, and Buchwald‐Hartwig cross‐coupling reactions. Notably, this strategy was successfully applied for parallel drug syntheses of ( E )‐ and ( Z )‐zimelidine, ( E )‐ and ( Z )‐tamoxifen, and Merck's cyclopropane pharmacophore. Representative successful utilizations by other groups are also introduced.