Palladium-catalyzed asymmetric [3+2] cycloaddition of trimethylenemethane with imines

Abstract

Trost and his coworkers investigated the asymmetric synthesis of pyrrolidines via [3+2] cycloaddition of trimethylenemethane (TMM) with imines using a phosphoramidite complex of palladium as catalyst. They tested several ligands and different classes of imine in order to determine which could best provide both high percent yield and high percent enantiomeric excess (ee). Among the 11 tested ligands (Scheme 1), L10 produced the best result by producing up to a 76% conversion and 84% ee. After determining the best ligand, the imine that could provide high ee and yield for the reaction was determined (Table 1). It was found that N-boc imine (entry 5, Table 1) was the best because it has produced 98% yield and 87% ee. Table 2 shows the effect of varying Boc-imine on the yield and ee of the product. Aromatic substitution patterns (entries 2-4) in the imine showed no distinct changes in the percent ee. In entries 10-12 wherein heterocycles were used as substrates, it was observed that the percent ee remains high, though decreases in percent yield occurred. When the amount of catalyst and ligand was reduced to half of the typical loading (entry 8), the decrease in yield and ee was insignificant. Lowering the temperature even to -15°C still provided high yield with moderate improvement in enantioselectivity. © 2007 Data Trace Publishing Company.