Enantioselective, N-heterocyclic carbene catalyzed annulations

The development of N-heterocyclic carbene (NHC)-catalyzed annulations via the catalytic generation of reaction intermediates has been described. We have developed the direct annulations of enals and N-sulfonylimines to synthesize gamma-lactams via homoenolates addition to imines. The key to the success is the choice of the protecting group on the imine to overcome nucleophilic inhibition.;Having achieved the protonation of homoenolates to afford enolates, we have discovered enantioselective, NHC-promoted, inverse electron demand Diels-Alder reactions. We have extended the enolate precursors from enals to alpha-chloroaldehydes and to the corresponding sodium bisulfite adducts. We have also shown that both azadienes and oxodienes are reactive substrates in the Diels-Alder cycloadditions. In these processes, low catalyst loadings have been achieved.;Finally, we have developed enantioselective, NHC-catalyzed bicyclo-beta-lactam formation via direct annulations of enals and unsaturated N-sulfonyl ketimines, which feature an benzoin-oxy-Cope cascade reaction.