Synthesis and evaluation of new chiral nonracemic C2-symmetric and unsymmetric 2,2′-bipyridyl ligands

Abstract

The synthesis of a series of chiral nonracemic and C₂-symmetric 2,2′-bipyridyl ligands (R = Me, i-Pr and Ph) as well as the syntheses of the corresponding unsymmetric 2,2′-bipyridyl ligands (R = Me and Ph) is described. These bipyridyl ligands were prepared, in a notably direct and modular fashion, from the readily available and corresponding 2-chloropyridine acetals (R = Me, i-Pr and Ph). The bipyridyl ligands were evaluated in copper(I)-catalyzed cyclopropanation reactions of styrene with the ethyl and t-butyl esters of diazoacetic acid. The stereoselectivities, as well as the yields of the cyclopropanation reactions, were dependant on the ratio of the bipyridyl ligands and copper triflate that was employed. The best result was obtained in the asymmetric cyclopropanation reaction of styrene and tert-butyl diazoacetate with the C₂-symmetric bipyridyl ligand (R = i-Pr). This afforded the corresponding trans-cyclopropane in good diastereoselectivity (4 : 1) and in moderate enantioselectivity (44% ee). The X-ray structure determination of a complex formed between the C₂-symmetric 2,2′-bipyridyl ligand (R = Ph) and copper(I) chloride showed that two bipyridyl ligands had coordinated to the copper(I) ion. This information, along with the results of a series of cyclopropanation reactions and NMR data, led to the conclusion that the 2,2′-bipyridyl ligands had the propensity to form catalytically inactive bis-ligated copper(I) species in solution that were in equilibrium with catalytically active copper(I) triflate and the desired mono-ligated copper(I) species. Moreover, it was observed that the complex of the bipyridyl ligand (R = Ph) and copper(I) chloride had a particularly large optical rotation (sodium D-line). The maximum positive optical rotation was subsequently found to be +1.1 × 10⁴ at 304 nm and the maximum negative optical rotation was −1.3 × 10⁴ at 329 nm.