Aminoalcohol-zinc Catalyzed Enantioselective Arylation Of N-diphenylphosphinoylimine

Enantiomerically pure diarylmethylamines are important intermediates in the synthesis of biologically active compounds and natural product. Such as cetirizine hydrochloride stands out from several drug candidates as a commercially important nonsedating antihistamine agent and SNC80 is a powerful tool with which to explore the role ofδopioid receptors in the central nervous system (CNS). Asymmetric addition of nucleophilic reagent to imines is one of the most straightforward and convenient methods to construct chirality diarylmethylamines.In the past few years, significant improvements have been made in this area, some good methods have been reported to from the important intermediates. For the reported papers, some expensive and harmful metal complexs were necessary. So some problem and inconvenient element will caused in the pharmaceutical synthesis for bring in the harmful metal. Meanwhile, some phosphite ligands which hardly in synthesis and keep were aslo used to catalyzed the reaction. In 2002, Stefan Brase used amine alcohol in combination with dimethylzinc and diphenylzinc effectively catalyze the direct asymmetric arylation of N-arylimines after arylation of aldehyde. The results shows that the arylation catalysis system have been reported for the carbonylcompound will also suit for imines despite lower reactivity. It was known that inexpensive and harmfulless compound of ZnEt2 and arylboroxines combinated amino alcohols were wildly reported to enantioselectieve arylation of aldehyde, this method have not been used for imines yet.We preparated the arylarylboroncompound by heating ZnEt2 and arylboroxines at 80℃for 8 hours and used proline-derivativedβ-amine alcohol as ligand to catalyze the enantioselectieve arylation of N-diphenylphosphinoylimine. aromatic, heteroaromatic, aliphatic andα,β-unsaturated N-(diphenylphosphinoyl) imines were investigated and Affording N-(diphenylphosphinoyl)-protected diarylmethylamines with high yields and good to excellent enantioselectivities. The resulting phosphonamide products aslo easily deprotected under mild conditions to give free diarylmethylamines.