Significant Improvement on Enantioselectivity and Diastereoselectivity of Organocatalyzed Asymmetric Aldol Reaction Using Helical Polyisocyanides Bearing Proline Pendants

A novel enantiopure phenyl isocyanide (1) carrying l-proline derivative was designed and synthesized. Living polymerization of 1 using a alkyne-Pd­(II) catalyst affording a series of helical poly-1 ms with controlled molecular weights (M ns) and narrow molecular weight distributions (M w/M ns) bearing l-proline ester as the pendants. Removed the protecting groups on the l-proline pendants lead to the formation of helical poly-1 m-A. Very interestingly, the left-handed backbone of poly-1 m was reversed to right-handed helix in poly-1 m-A as revealed by circular dichroism (CD) and polarimetry. Optically active helical poly-1 m-A showed excellent catalytic ability on asymmetric aldol reaction. Comparing to the small molecule (1-A) with similar structure, both the enantioselectivity and the diastereoselectivity of the aldol reaction were significantly enhanced. The enantiomeric excess (ee) and diastereomeric ratio (dr) values of the aldol reaction are up to 95% and >20/1, respectively. Moreover, the helical polyisocyanides catalyst can be easily recovered and reused in the aldol reaction at least four cycles without significant loss of its enantioselectivity and diastereoselectivity.