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.