Synthetic and quantum mechanical studies into the N-heterocyclic carbene catalyzed (4+2) cycloaddition

Sarah Jean Ryan, Andreas Stasch, M N Paddon-Row, David Lupton

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Abstract

The N-heterocyclic carbene catalyzed (4 + 2) cycloaddition between alpha,/beta-unsaturated acid fluorides and TMS dienol ethers provides cyclohexene fused beta-lactone intermediates stable below -20 degrees C. These can be intercepted reductively or with organolithium reagents to produce diastereomerically pure cyclohexenes (>20:1 dr) with up to four contiguous stereocenters. The mechanism has been investigated using theoretical calculations and by examining secondary kinetic isotope effects. Together these studies implicate the formation of a diastereomerically pure beta-lactone intermediate by a stepwise (4 + 2) cycloaddition involving Michael addition, aldol cyclization, and lactonization.
Original languageEnglish
Pages (from-to)1113 - 1124
Number of pages12
JournalThe Journal of Organic Chemistry
Volume77
Issue number2
DOIs
Publication statusPublished - 2012

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