Cooperative N‑heterocyclic Carbene and Iridium Catalysis Enables Stereoselective and Regiodivergent [3 + 2] and [3 + 3] Annulation Reactions

A cooperative N-heterocyclic carbene
(NHC)/iridium catalysis has
been developed to achieve highly stereoselective and regiodivergent
[3 + 2] and [3 + 3] annulation reactions of 2-indolyl allyl carbonates
with enals. The use of the NHC catalyst has introduced switchable
homoenolate and enolate intermediates from the common enal precursor
via a simple adjustment of reaction conditions in a predictable manner.
This protocol furnishes two types of biologically important products,
pyrrolo­[1,2-a]­indoles and pyridine­[1,2-a]­indoles, with high diastereo- and enantioselectivities (up to >20:1
dr and >99% ee). Notably, all four stereoisomers of these products
with two vicinal stereocenters could be afforded through permutations
of the enantiomers of the two chiral catalysts. Mechanistic investigations
and further computational density functional theory calculations give
an explanation of the origin of the regioselectivity. In addition,
the NHC-enolate intermediate generated from formylcyclopropanes was
also compatible in this cooperative catalytic system and thus the
arsenal of optically pure pyrrolo­[1,2-a]­indole products
was enriched.