Phosphine-Catalyzed Enantioselective Intramolecular [3+2] Annulations To Generate Fused Ring Systems

Substantial
progress has been described in the development of asymmetric
variants of the phosphine-catalyzed intermolecular
[3+2] annulation of allenes with alkenes; however, there have not
been corresponding advances for the intramolecular
process, which can generate a higher level of complexity (an additional
ring and stereocenter(s)). In this study, we describe the application
of chiral phosphepine catalysts to address this challenge, thereby
providing access to useful scaffolds that are found in bioactive compounds,
including diquinane and quinolin-2-one derivatives, with very good
stereoselectivity. The products of the [3+2] annulation can be readily
transformed into structures that are even more stereochemically rich.
Mechanistic studies are consistent with β addition of the phosphepine
to the allene being the turnover-limiting step of the catalytic cycle,
followed by a concerted [3+2] cycloaddition to the pendant olefin.