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 m s with controlled molecular weights ( M n s) and narrow molecular weight distributions ( M w / M n s) 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.