New hybrid ligands with a trans-1,2-diaminocyclohexane backbone: Competing chelation modes in palladium-catalyzed enantioselective allylic alkylation

Abstract

Three new hybrid ligands with trans-1,2-diaminocyclohexane backbone have been synthesized from (1R,2R)-2-aminocyclohexylcarbamic acid tert-butyl ester (4), which is prepared through an indirect monoprotection of the diamine. The ligands are (1R,2R)-N-{2-[2-(dimethylamino)benzoyl]amino}-cyclohexyl-2-(diphenylphosphanyl)benzamide and its di-n-butylamino- and diphenylamino-derivatives (3a-c), which belong to formal P,N-type chelates with possible wide bite angles in the metal chelation. To evaluate the new hybrid ligands against well-known P,N- and P,P-chelates (1 and 2), they were employed in the palladium-catalyzed allylic alkylations between two standard racemic allylic acetates, 2-acetoxy-1,3-diphenyl-2-propene (14a) and 2-acetoxy-1,3-dimethyl-2-propene (14b), and dimethyl malonate under different reaction conditions. The catalytic system with the new ligands showed good reactivity toward both the substrates with moderate enantioselectivities (up to 78% ee toward 14a and 80% ee toward 14b). Of particular note, dramatic changes in the sense and in the degree of the enantioselectivity were observed depending on the ligands and reaction conditions, which suggested a different chelation mode was competing with the supposed P,N-chelation mode. An X-ray crystal structure of a chelated palladium complex [Pd(3c)(eta (3)-PhCHCHCHPh)]PF6 was obtained, which showed a P,O-chelation mode in which a carboxamide oxygen acted as the O-ligand. This is the first example of the enantioselective palladium-catalyzed allylic alkylation in which a P,O-chelated complex of a carboxamide group participated as the ligand group.