Bifunctional iminophosphorane organocatalysts for enantioselective synthesis: application to the trifluoromethyl aryl ketimine nitro-Mannich reaction

Bifunctional iminophosphoranes (BIMP) represent a class of so-named organic superbases which can be used as organocatalysts to promote several reactions. Thanks to their highly modular design, typically incorporating a variable H-bond donor moiety, a chiral amino acid-derived scaffold, and a phosphine-derived iminophosphorane superbase, in recent years they have enabled unprecedented performances in enantioselective Brønsted base catalysis, allowing to access to high pKa pronucleophiles. Thiourea-based iminophosphorane organocatalysts featuring SPhos or BIDIME phosphine units, derived from the combination via Staudinger reaction of a chiral 1,2-amino alcohol-derived thiourea-organoazide with electron-rich phosphines, have been developed and successfully applied in the asymmetric addition of nitromethane to N-Boc-protected trifluoromethyl aryl ketimines. α-Trifluoromethyl β-nitroamines, featuring a tetrasubstituted stereocenter, were obtained in good to excellent yields and enantioselectivities. The reaction was performed also on gram scale, without loss of enantioselectivity.