Asymmetric aza-Henry reaction under phase transfer catalysis: an experimental and theoretical study.
An efficient catalytic asymmetric aza-Henry reaction under phase transfer conditions is presented. The method is based on the reaction of the respective nitroalkane with alpha-amido sulfones effected by CsOH x H2O base in toluene as solvent and in the presence of cinchone-derived ammonium catalysts. This direct aza-Henry reaction presents as interesting features its validity for both nonenolizable and enolizable aldehyde-derived azomethines and the tolerance of nitroalkanes, other than nitromethane, for the production of beta-nitroamines. The synthetic value of the methodology described is demonstrated by providing (a) a direct route for the asymmetric synthesis of differently substituted 1,2-diamines and (b) a new asymmetric synthesis of gamma-amino alpha,beta-unsaturated esters through a catalytic, highly enantioselective formal addition of functionalized alkenyl groups to azomethines. Finally, a preferred TS that nicely fits the observed enantioselectivity has been identified. Most remarkable, an unusual hydrogen bond pattern for the catalyst-nitrocompound-imine complex is predicted, where the catalyst OH group interacts with the NO2 group of the nitrocompound.
Departamento de Química Orgánica I, Facultad de Química, Universidad del País Vasco, Apdo. 1072, San Sebastián, 20080, Spain.
Enrique
E
Gomez-Bengoa
Anthony
A
Linden
Rosa
R
López
Idoia
I
Múgica-Mendiola
Mikel
M
Oiarbide
Claudio
C
Palomo