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Coumarins by Direct Annulation: β‐Borylacrylates as Ambiphilic C 3 ‐Synthons
Author(s) -
Wienhold Max,
Molloy John J.,
Daniliuc Constantin G.,
Gilmour Ryan
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202012099
Subject(s) - annulation , synthon , chemistry , combinatorial chemistry , sonogashira coupling , stereochemistry , drug discovery , cyclohexenone , organic chemistry , catalysis , palladium , biochemistry
Modular β‐borylacrylates have been validated as programmable, ambiphilic C 3 ‐synthons in the cascade annulation of 2‐halo‐phenol derivatives to generate structurally and electronically diverse coumarins. Key to this [3+3] disconnection is the BPin unit which serves a dual purpose as both a traceless linker for C(sp 2 )–C(sp 2 ) coupling, and as a chromophore extension to enable inversion of the alkene geometry via selective energy transfer catalysis. Mild isomerisation is a pre‐condition to access 3‐substituted coumarins and provides a handle for divergence. The method is showcased in the synthesis of representative natural products that contain this venerable chemotype. Facile entry into π‐expanded estrone derivatives modified at the A‐ring is disclosed to demonstrate the potential of the method in bioassay development or in drug repurposing.