Organic Chemistry: Current Research
Open Access

Mechanistically degenerate kinetic resolution in [5+2] cycloisomerization

10^th European Organic Chemistry Congress

March 21-22, 2019 | Rome, Italy

Kai Ma

Oxford, United Kingdom

Posters & Accepted Abstracts: Organic Chem Curr Res

Abstract :

Kinetic resolution is a highly attractive strategy for the synthesis of enantioenriched compounds from racemic starting materials, whereby one enantiomer of a substrate reacts in preference, or in a different manner, to the other. In the field of asymmetric transition metal-catalyzed cycloisomerization, where acyclic starting materials are converted to relatively complex cyclic (chiral) products under the influence of a chiral metal catalyst, kinetic resolutions are scarce – and to date unknown for the [5+2] cycloisomerization of vinylcyclopropanes, a venerable method for the synthesis of seven-membered rings. Here we show how a rhodium(I)-phosphoramidite catalyst is able to effect the first examples of kinetic resolution in [5+2] cycloisomerization. Depending on the substrate, either a classical resolution (where one enantiomer remains unreacted), or a diastereodivergent resolution (in which each enantiomer gives a different product diastereomer) are achieved, both with exceptional selectivity. This difference in the mode of resolution is shown to arise from a divergence in the mechanistic pathway followed, as supported by detailed theoretical studies; such mechanistic degeneracy is, to our knowledge, unprecedented in the wider arena of kinetic resolution. The chemistry operates across a range of vinylcyclopropane substrates, and includes the first example of kinetic resolution by cycloisomerization of a chiral silane, as well as an application to natural product synthesis through resolution of an allenyl vinylcyclopropane..