Water-Compatible Hydrogen-Bond Activation: A Scalable and Organocatalytic Model for the Stereoselective Multicomponent Aza-Henry.

Trabajo presentado en el 6th ORCA Meeting (Cost Action on organocatalysis) celebrado en Palermo (Italia) del 07 al 10 de mayo de 2014.

In this communication we described the development and implementation of the first example of a hydrogen bond based organocatalytic multicomponent manifold operating “in the presence of water” conditions. The manifold performs a multicomponent and stereoselective version of the organocatalyzed aza-Henry reaction and it utilizes aniline, aromatic or aliphatic aldehydes, primary or secondary nitroalkanes, N,N-dimethylcyclohexylamine as the catalytic base and a chiral thiourea or squaramide catalyst as the chiral source to afford the corresponding -disubstituted -nitroamine derivatives. The reaction does not require a large excess of nitroalkane (two equivalents are enough) to afford the corresponding product in good yield and high stereoselectivity (up to ≥99.5:0.5 e.r. and ≥99.5:0.5 d.r., anti-adduct). The catalysis is performed through H-bond interactions between the nitroalkane and the chiral catalyst in the presence of interfacial water. Importantly, each family of catalysts delivers the -nitroamine product with complementary enantioselectivity, allowing for the selective access to the two enantiomeric series of these building blocks in an efficient, instrumentally simple and scalable manner.