Chemistry: A European Journal 2015-06-26

Highly Functionalized Cyclopentane Derivatives by Tandem Michael Addition/Radical Cyclization/Oxygenation Reactions.

Martin Holan, Radek Pohl, Ivana Císařová, Blanka Klepetářová, Peter G Jones, Ullrich Jahn

Index: Chemistry 21 , 9877-88, (2015)

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Abstract

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 C-C bonds and one C-O 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.© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.