Catalytic Enantioselective Diethylzinc Addition to N-Phosphinoylimine Using Thiophosphoramide of Homologated Binaphthyl N,O-Ligand

Abstract

Catalytic enantioselective reactions that convert imines to α-chiral amines hold an important place in asymmetric synthesis, because these chiral amines are among the most common chiral subunits of biologically active molecules. The success of forming an α-chiral amine from an imine depends heavily on the electrophilicity of the imine and the nucleophilicity of the organometals, as well as on the amounts of chiral ligands. Several effective catalytic enantioselective addition reactions of organozinc reagents to activated aryl-, acyl-, or sulfonylimines have been reported, but the addition products require harsh oxidizing, reducing or acidic conditions for the free amino group. Due to the relatively mild revealing conditions that are required in the case where N-(diphenylphosphinoyl)imines (1) are used as activated substrates, this method is receiving increasing attention. However, as a result of the lower electrophilicity of these imines, significant amounts of chiral ligands (up to one equiv) and an excess of organozincs (up to 10 equiv) are required to ensure high conversion and enantioselectivity. Recently, two practical catalytic asymmetric organozinc additions to N-(diphenylphosphinoyl)imines were reported with the use of chiral diphosphine or thiophosphoramide ligands together with Cu(OTf)2 as the catalytic precursor. It is generally believed that organocopper intermediates are involved in these nucleophilic organozinc addition reactions. In our previous reports, highly enantioselective additions of organozincs to aldehydes were accomplished using homologated binaphthyl N,Oligands (2) which showed much improved enantioselectivity compared with the corresponding binaphthyl N,Oligand (NOBIN). Thus, we were interested in investigating the application of these homo-NOBINs and their phosphoramide derivatives to the enantioselective additions of organozincs to N-phosphinoylimines.