A cascade reaction of N-aryl-α,β-unsaturated nitrones and electron-deficient allenes has been discovered that allows single-step access to 3-functionalized indoles that usually require preformation and alkylation of an indole precursor. The heterocycles prepared through the hydrogen bond donor catalyzed cascade reaction are poised to undergo a McMurry coupling to form previously synthetically elusive cycloheptanone-fused indoles. The scope of these transformations is discussed as well as mechanistic experiments describing proposed intermediates of the cascade reaction and an initial catalytic asymmetric example that generates a carbon stereocenter during the cascade process.

Cascade reactions involving nitrones and allenes are known to facilitate the rapid synthesis of several indole derivatives. The chemoselectivity of these complicated transformations can be influenced by substrate functionalization, reaction conditions, and catalyst control. While seminal studies established primary reactivity patterns, recent work has illustrated the impact of these cascade reactions for creating diverse libraries, increased the breadth of these methods with facilitated access to challenging nitrones, and shown that these transformations can be controlled by asymmetric catalysis.

A new cascade reaction provides convergent access to novel bridged bicyclic medium-sized N-heterocycles.

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