Understanding the regio- and chemoselective polar [3+2] cycloaddition of the Padwa carbonyl ylides with α-methylene ketones. A DFT study

The regio- and chemoselective polar [3+2] cycloaddition (32CA) of the Padwa carbonyl ylide (CY) with alpha-methylene ketone (alpha MK) to yield the oxa-bridged spirocycloadduct has been studied using the DFT method at the B3LYP/6-31G(d) computational level. Six reactive channels associated to the stereo-, regio-, and chemoselective approach modes of the CY to the C=C and C=O reactive sites of the alpha MK have been analyzed. DFT calculations for this cycloaddition are in complete agreement with the experimental outcome, explaining the reactivity and selectivity of the formation of the [3+2] cycloadduct. Analysis of the global and local electrophilicity and nucleophilicity indices allows an explanation about the regio-and chemoselectivity of this 32CA reaction. Intrinsic reaction coordinate (IRC) calculations and the topological analysis of the electron localization function (ELF) of the relevant points of the favored reactive channel explain the one-step two-stage nature of the mechanism of this cycloaddition. (C) 2009 Elsevier Ltd. All rights reserved.