Enantioselective Addition (Asymmetric Pudovik Reaction) Of Dialkyl Phosphite To Aldehydes Cat-alyzed By Chiral BINOL-Zn Complex

Chiralα-hydroxy phosphonates and their derivatives are widely applied in the pharmaceutical industry owing to their biological activity. Studies show that chiralα-hydroxy phosphonates are important intermediates, which can be used toα-substituted phosphoryl compounds synthesizing. There are three methods to get access toα-hydroxy phosphonates, including optical resolution,chiral reduction and asymmetric catalysis. The most popular method of preparation ofα-hydroxy phosphonates is the asymmetric hydrophosphonylation of aldehydes catalyzed by chiral metal complex.So far, aluminum, lithium and titanium are widely used to catalyze this reaction. Searching for a new metal complex system that could achieve high reactivity and enantioselectivity is still challenging and interesting.We found that C2-axial chiral ligand L19 synthesized by (R)-(-)-2,2'-Dihydroxy-1,1'-binaphthyl and (S)-dipheny-(pyrrolidin-2-yl)methanol can catalyze this reaction with high reactivity and enantioselectivity. The complex composed by L19 and 2 mol equivalent diethylzinc can catalyze addition of phosphite to aldehyde, the products are chiralα-hydroxy phosphonates with yield up to 99% and ee up to 94%. In addition,the Synthesis methods of L19 is easy.