Synthesis of hybrid phosphinoferrocene ligands bearing amine pendants and catalytic evaluation of their gold(I) complexes

Abstract

A series of hybrid, ferrocene-based phosphines bearing additional amine substituents has been synthesized and evaluated in gold catalysis. The series includes 1,1′- and 1,2-disubstituted phosphinoferrocene donors with cyclic or acyclic amine groups (morpholine, thiomorpholine, and dimethylamine) and various substituents on the phosphorus atom (phenyl, cyclohexyl, and 2-furyl). The compounds were prepared using two complementary routes: (1) alkylation of a sulfide-protected phosphine–amine intermediate and (2) copper-catalyzed electrophilic amination followed by a lithiation/phosphinylation step. The corresponding chlorogold(I) complexes [AuCl(L-κP)], obtained in high yields and structurally characterized, were evaluated as precatalysts in intramolecular cyclization of N-propargylbenzamide into 4,5-dihydro-5-methylene-2-phenyloxazole and oxidative cyclization of phenylacetylene with acetonitrile (using pyridine N-oxide as the oxidant) to 2-methyl-5-phenyl-1,3-oxazole. Catalytic studies revealed that the nature of the amine and phosphine substituents strongly influence the catalyst performance. Compared with their 1,2-disubstituted (homoannular) analogs, the complexes obtained from 1,1′-disubstituted (heteroannular) ligands generally exhibited faster reaction rates. In addition, a specific structural distortion of the ferrocene unit comprising the bending of the N-bound cyclopentadienyl carbon atom from the ring plane was detected in the structures of compounds bearing an amine group as the sole substituent on the cyclopentadienyl ring. This distortion was rationalized using DFT calculations as a consequence of the mesomeric effect of the amine moiety, which affects the electron distribution in the cyclopentadienyl ring.