New route to chiral triarylmethanes

31 Jul 2015 NUS chemists reported a new synthetic procedure for chiral triarylmethanes, which is realized by rhodium-catalyzed asymmetric arylation of diarylmethylamines.

One of the most important matters in synthetic organic chemistry is to find a new method of synthesizing chemicals of practical or potential importance. The chiral triarylmethanes, where the stereogenic carbon center is substituted with three different aromatic groups, are known to be a very important class of compounds because of their high utility in medicinal chemistry and materials science.

A team led by Prof Tamio HAYASHI from the Department of Chemistry in NUS and Institute of Materials Research and Engineering (IMRE), has found a new synthetic route to chiral triarylmethanes, using an asymmetric substitution reaction of diarylmethylamines with arylboron reagents in the presence of a rhodium catalyst coordinated with chiral diene ligand (see Figure). The present method has high applicability for the synthesis of a variety of chiral triarylmethanes.

The team has developed catalytic asymmetric carbon-carbon bond forming reactions, which is asymmetric conjugate addition of organoboron reagents to electron-deficient olefins, typically α,β-unsaturated carbonyl compounds, in the presence of chiral rhodium complexes. Recently, they have found chiral ligands of conceptual novelty, that is, chiral dienes whose basic diene skeleton is norbornadiene or bicyclooctadiene. They have two alkyl or aryl substituents on the double bonds, one on each of the two double bonds. The chiral diene ligands were found to be better than the conventional chiral ligands represented by chiral bisphosphines in terms of both catalytic activity and enantioselectivity in some of the catalytic asymmetric reactions. This method facilitates the synthesis of, for example, chiral triarylmethane-based molecular propellers. Presently, the team is studying on the asymmetric synthesis of some other chiral molecules, which is based on the accumulated knowledge and understanding of the rhodium-catalyzed asymmetric reactions.


This figure shows the reaction of racemic diarylmethylamines, (Ar1Ar2CHNR2), where Ar1 is substituted with a 2-hydroxy group, with arylboroxines (Ar3BO)3 in the presence of a chiral diene-rhodium catalyst gave high yields of chiral triarylmethanes (Ar1Ar2CH*Ar3) with high enantioselectivity (up to 97% ee). The reaction is assumed to proceed through o-quinone methide intermediates which undergo Rh-catalyzed asymmetric 1,4-addition of the arylboron reagents. [Image credit: Tamio HAYASHI]



Huang Y, Hayashi T. “Asymmetric Synthesis of Triarylmethanes by Rhodium-Catalyzed Enantioselective Arylation of Diarylmethylamines with Arylboroxines.” Journal of the American Chemical Society 137 (2015) 7556.