Practical Enantioselective Arylation and Heteroarylation of Aldehydes with In Situ Prepared Organotitanium Reagents Catalyzed by 3‐Aryl‐H8‐BINOL‐Derived Titanium Complexes

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 ( 3 d ; DPP=3,5‐diphenylphenyl) and DTBP‐H₈‐BINOL ( 3 e ; 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.