Efficient asymmetric copper(I)-catalyzed henry reaction using chiral N-alkyl-C₁-tetrahydro-1,1′-bisisoquinolines

A series of closely related chiral N-alkyl-C₁-tetrahydro-1, 1′-bisisoquinoline ligands only differing in the steric bulk of the alkyl groups has been examined in the asymmetric Henry reaction. A complex derived from the (R)-N-methyl-1′,2′,3′,4′-tetrahydro-1,1′- bisisoquinoline and copper(I) chloride proved to be a very efficient catalyst system that can promote the reaction of a wide range of aromatic and aliphatic aldehydes to give the expected nitroalcohol products in high yields (up to 99 %), excellent enantioselectivities (up to 94 % ee), and moderate diastereoselectivities (up to 1.6:1). This catalyst system is very general, requires no additives for activation, and is also simple in operation because no special precautions are taken to exclude moisture or air from the reaction flask.