Department of Chemistry, Roy and Diana Vagelos Laboratories, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Am Chem Soc. 2012 Jul 25;134(29):12098-103. doi: 10.1021/ja302761d. Epub 2012 Jul 16.
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 interactions are identified that enable high selectivity: an oxyanion-steering mechanism and a CH-π interaction. The calculations accurately predict the enantioselectivity of a number of N-heterocyclic carbene catalysts in the hetero-Diels-Alder reaction.
N-杂环卡宾催化的[4+2]环加成反应已被证明可以极好的对映选择性和非对映选择性生成γ,δ-不饱和δ-内酰胺。然而，对中间烯醇化物的几何形状的初步计算研究使得选择性的起源和反应途径都变得不确定。在这里，我们表明，发生了协同的，但高度异步的 Diels-Alder 反应，而不是逐步的 Michael 型或 Claisen 型途径。此外，确定了两个关键的相互作用，从而实现了高选择性：氧阴离子导向机制和 CH-π相互作用。这些计算准确地预测了 N-杂环卡宾催化剂在杂 Diels-Alder 反应中的对映选择性。
