Practical enantioselective arylation and heteroarylation of aldehydes with in situ prepared organotitanium reagents catalyzed by 3-aryl-H8-BINOL-derived titanium complexes.

ABSTRACT

A highly efficient and practical method for the catalytic enantioselective arylation and heteroarylation of aldehydes with organotitanium reagents, prepared in situ by the reaction of aryl- and heteroaryllithium reagents with ClTi(OiPr)3, is described. Titanium complexes derived from DPP-H8 -BINOL (3d; DPP=3,5-diphenylphenyl) and DTBP-H8 -BINOL (3e; DTBP=3,5-di-tert-butylphenyl) exhibit excellent catalytic activity in terms of enantioselectivity and turnover efficiency for the transformation, providing diaryl-, aryl heteroaryl-, and diheteroarylmethanol derivatives in high enantioselectivity at low catalyst loading (0.2-2 mol%). The reaction begins with a variety of aryl and heteroaryl bromides through their conversion into organolithium intermediates by Br/Li exchange with nBuLi, thus providing straightforward access to a range of enantioenriched alcohols from commercially available starting materials. Various 2-thienylmethanols can be synthesized enantioselectively by using commercially available 2-thienyllithium in THF. The reaction can be carried out on a 10 mmol scale at 0.5 mol% catalyst loading, demonstrating its preparative utility.