Catalysis of the Hajos-Parrish-Eder-Sauer-Wiechert reaction by cis- and trans-4,5-methanoprolines:: Sensitivity of proline catalysis to pyrrolidine ring conformation

Methanoprolines are found to be catalysts for the Hajos-Parrish-Eder-Sauer-Wiechert reaction.([1]) cis-4,5-Methanoproline exhibits catalytic ability similar to proline (86% yield, 93% ee), whereas the trans-4,5-methanoproline is less selective (67% yield, 83% ee) and shows less acceleration. The reaction was also studied with hybrid density functional theory (B3LYP). The nearly planar cis-4,5-methanoproline amine better reflects the planar iminium of the transition states than the pyramidalized trans-4,5-methanoproline. This difference in conformation is responsible for the observed higher enantioselectivity and enhanced catalytic behavior of the cis-4,5-methanoproline.