Diastereoselective addition of allylmetal compounds to imines derived from (S)-1-phenylethanamine

The sense of asymmetric induction and the degree of diastereoselectivity in the addition of allylmetal compounds to imines derived from aldehydes and (S)-1-phenylethanamine is affected by the nature of the imine and of the metal. Allyl-BBN, -MgX, -ZnBr, -Cu, and diallylcuprate attacked the Si face of the imine derived from 2-methylpropanal. Conversely, the Re face of aromatic aldimines was generally attacked, but the behaviour of the magnesium reagent was variable. Best results were achieved with allyl-BBN and diallyl cuprate (de up to 98% at -78 degrees C) with both aliphatic and aromatic imines. However, the use of allylzinc bromide and allyl(dichloro)iodotin was preferable with the bidentate pyridine-2-imine (de 70%, Re face addition). The cleavage of the chiral auxiliary (ammonium formate-palladium on carbon-methanol, 65 degrees C, 2 h) occurred regioselectively, with concomitant hydrogenation of the unsaturated chain, only on the dibenzylic amine obtained by the reactions of (S)-2,5-dimethoxybenzaldimine with allyl-BBN (de 94%) and dially cuprate (de 99%). This allowed the expeditious and efficient synthesis of (R)-(+)-1-(2,5-dimethoxyphenyl)butanamine (80% overall yield) and, at the same time, the confident assignment of the configuration to the homoallylic amines obtained from the aromatic aldimines, previously undetermined. The opposite sense of asymmetric induction observed in the reaction of aliphatic vs. aromatic aldimines was attributed to the isomerization of E- to Z-aromatic imines prior to the C-C bond formation. Several six-membered chair or boat cyclic transition states, featuring different dispositions of the auxiliary and pi-stacking of aryl groups, have been empirically examined.