Synthesis Of Chiral Phosphite-Pyridine Ligands And Their Applications In 1, 4-Conjugate Addition

A new type of phosphite-pyridine ligands derived from chifal NOBESJ and BINOL were designed, synthesized and employed in Cu(I)-catalyzed enantioselective 1,4-conjugate addition of EtiZn to enones. The results demonstrated that the ligands derived from (S)-NOBIN and (S)-BINOL were matched for the high enantioselectivity; the BINOL moiety played a pivotal role in the absolute configuration of the addition products. The nitrogen in pyridine coordinated to the metal center Cu(I) and the 6-Me in pyridine exerted an important effect on the product enantioselectivities. Ligand (S,S)-La afforded good enantioselectivities in the addition reaction of Et2Zn to trans-4-aryl-3-buten-2-one. The ligand (S,S)-Lc was better for chalcones, and up to 97.1 % was achieved. To our knowledge, this was one of the best results in this kind of reactions.We synthesized a new type of Hg-binaphthyl-phosphite-pyridine ligands Lk-Lp and systematically studied their application in Cu(I)-catalyzed 1,4-conjugate additions of EtaZn to enones. The results showed the ligand (S, S)-Ll derived from (S)-H8-NOBIN and (5)-BINOL backbone afforded high enantioselectivities for various chalcones. The corresponding ligand (S,S)-Lk achieved very high ee values for tans-4-aryl-3-buten-2-one substrates, and up to 97.8 % ee has been obtained.To the best of our knowledge, this is the best result for the enantioselective 1,4-conjugate addition of Et2Zn to /raw5-4-aryl-3-buten-2-one.A clear positive nonlinear effect of the enantioselectivity of ligand LA on the product ee was observed in the enantioselective 1,4-conjugate addition. The experimental data met Kagan's MLj model.We observed a variation of the product absolute configuration with temperature in the Cu(I)-phosphite-pyridine complex catalyzed 1,4-conjugate addition of EtaZn to enones.