Novel Transition Metal or Phosphine-Mediated Bond Activations for C-C/C-X Bond Formations

For decades, cycloaddition reactions have been a staple in the organic chemist’s toolbox, providing access to a variety of biologically interesting heterocyclic compounds. In particular, [4+n]-cycloadditions have been utilized extensively to access, five, six, and seven-membered rings with a range of substitution patterns. Our interest lied in the [4+1]-construction of potentially bioactive five-membered heterocycles, which are commonly constructed via a [3+2]-cycloaddition reaction between a 1,3-dipole and a dipolarophile. While this is an elegant approach, it is limited by the high level of reactivity of the starting materials.

With this is mind, we anticipated that the [4+1] retrosynthetic disconnect would be an efficiacious approach providing ready access to the desired heterocycles without the chemoselectivity and regioselectivity challenges that can arise with [3+2] cycloadditions. Additionally, the variety of four atom components available would allow access to multiple heterocyclic motifs. Towards that end, we successfully employed aza ortho-quinone methides, aroyl isocyanates, vinyl ketenes, and vinyl allenes as four atom components in conjunction with metal-stabilized carbenes or phosphorus-based carbenoids as C1-synthons to generate dihydroindoles, oxazolones, and spirooxindole cyclopentenones.