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Updated: Mar 28, 2026

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Cascade Mn-Mediated γ-Alkylation/oxa-Michael Addition of Enones with 1,3-Dicarbonyls
Xiaoguang Liu1, Xiaohong Chen1, Justin T Mohr2
1Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois, 60607, USA.
Abstract:
A radical-based strategy for regioselective γ-C-C bond formation/oxa-conjugate addition, forming the tetrahydrobenzofuran core common to many bioactive natural products is described. The technique utilizes readily available enone derivatives and 1,3-dicarbonyl compounds as coupling partners in an oxidative formal [3+2] cycloaddition mediated by Mn(III) . The transformation delivers polycyclic products in good yields and proceeds with complete regiocontrol and excellent stereoselectivity. Sterically encumbered substrates are notably well-tolerated and bond formation occurs readily to form neopentyl and all-carbon quaternary centers in good yields. Several stereo- and chemoselective transformations of the products are described.
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In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...

