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Oxyanion steering and CH-? interactions as key elements in an N-heterocyclic carbene-catalyzed [4 + 2] cycloaddition.

ABSTRACT: The N-heterocyclic carbene catalyzed [4 + 2] cycloaddition has been shown to give ?,?-unsaturated ?-lactones in excellent enantio- and diastereoselectivity. However, preliminary computational studies of the geometry of the intermediate enolate rendered ambiguous both the origins of selectivity and the reaction pathway. Here, we show that a concerted, but highly asynchronous, Diels-Alder reaction occurs rather than the stepwise Michael-type or Claisen-type pathways. In addition, two crucial interactions are identified that enable high selectivity: an oxyanion-steering mechanism and a CH-? interaction. The calculations accurately predict the enantioselectivity of a number of N-heterocyclic carbene catalysts in the hetero-Diels-Alder reaction.

SUBMITTER: Allen SE

PROVIDER: S-EPMC3405918 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Oxyanion steering and CH-π interactions as key elements in an N-heterocyclic carbene-catalyzed [4 + 2] cycloaddition.

Allen Scott E SE Mahatthananchai Jessada J Bode Jeffrey W JW Kozlowski Marisa C MC

Journal of the American Chemical Society 20120716 29

The N-heterocyclic carbene catalyzed [4 + 2] cycloaddition has been shown to give γ,δ-unsaturated δ-lactones in excellent enantio- and diastereoselectivity. However, preliminary computational studies of the geometry of the intermediate enolate rendered ambiguous both the origins of selectivity and the reaction pathway. Here, we show that a concerted, but highly asynchronous, Diels-Alder reaction occurs rather than the stepwise Michael-type or Claisen-type pathways. In addition, two crucial inter ...[more]

PMID: 22765294

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