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Copper‐Catalyzed Double Additions and Radical Cyclization Cascades in the Re‐Engineering of the Antibacterial Pleuromutilin
Author(s) -
Ruscoe Rebecca E.,
Fazakerley Neal J.,
Huang Huanming,
Flitsch Sabine,
Procter David J.
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201504343
Subject(s) - semisynthesis , chemistry , combinatorial chemistry , radical cyclization , natural product , catalysis , copper , sequence (biology) , organic chemistry , biochemistry
A general synthetic sequence involving simply prepared starting materials provides rapid access to diverse, novel tricyclic architectures inspired by pleuromutilin. Sm II ‐mediated radical cyclization cascades of dialdehydes, prepared using a new, one‐pot, copper‐catalyzed double organomagnesium addition to β‐chlorocyclohexenone, proceed with complete sequence selectivity and typically with high diastereocontrol to give analogues of the target core. Our expedient approach (ca. 7 steps) allows non‐traditional, de novo synthetic access to analogues of the important antibacterial that can′t be prepared from the natural product by semisynthesis.