Premium
Highly Functionalized Cyclopentane Derivatives by Tandem Michael Addition/Radical Cyclization/Oxygenation Reactions
Author(s) -
Holan Martin,
Pohl Radek,
Císařová Ivana,
Klepetářová Blanka,
Jones Peter G.,
Jahn Ullrich
Publication year - 2015
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.201500424
Subject(s) - cyclopentane , tandem , michael reaction , chemistry , oxygenation , tandem accelerator , combinatorial chemistry , organic chemistry , catalysis , materials science , medicine , ion , composite material , anesthesia
Densely functionalized cyclopentane derivatives with up to four consecutive stereocenters are assembled by a tandem Michael addition/single‐electron transfer oxidation/radical cyclization/oxygenation strategy mediated by ferrocenium hexafluorophosphate, a recyclable, less toxic single‐electron transfer oxidant. Ester enolates were coupled with α‐benzylidene and α‐alkylidene β‐dicarbonyl compounds with switchable diastereoselectivity. This pivotal steering element subsequently controls the diastereoselectivity of the radical cyclization step. The substitution pattern of the radical cyclization acceptor enables a switch of the cyclization mode from a 5‐ exo pattern for terminally substituted olefin units to a 6‐ endo mode for internally substituted acceptors. The oxidative anionic/radical strategy also allows efficient termination by oxygenation with the free radical 2,2,6,6‐tetramethyl‐1‐piperidinoxyl, and two CC bonds and one CO bond are thus formed in the sequence. A stereochemical model is proposed that accounts for all of the experimental results and allows the prediction of the stereochemical outcome. Further transformations of the synthesized cyclopentanes are reported.