Enantioselective Organocatalytic Addition of Nitromethane to Trifluoromethylaryl Ketoimines Promoted by Electron-Rich Bifunctional Iminophosphoranes

Thiourea-based iminophosphorane (BIMP) organocatalysts featuring SPhos- or BI- DIME phosphine units have been developed and successfully applied in the asymmetric addition of nitromethane to N-Boc-protected trifluoromethyl aryl ketimines. α-Trifluoromethyl β-nitroamines were obtained in 40–82% isolated yields and 80– 95% enantioselectivities. A careful evaluation of the catalytic activity of BIMPs indicates that the catalysts derived from the combination via Stau- dinger reaction of a chiral 1,2-amino alcohol- derived thiourea-organoazide with electron-rich phosphines, promote the aza-Henry reaction on fluorinated ketimines with the highest enantioselec- tivity, leading to the amine featuring a tetrasubsti- tuted stereocenter in up to 95% ee. The reaction was performed also on gram scale, without loss of enantioselectivity.