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.

A general method has been developed for preparing enantioenriched secondary alcohols by starting from aryl bromides and aldehydes. Aryl bromides were first treated with BuLi, and the resulting aryllithium reagents were mixed with titanium tetraisopropoxide and magnesium bromide. The reaction of aldehydes with the resulting mixed titanium reagents, in the presence of 3-(3,5-diphenylphenyl)-H₈-BINOL (2 mol-%) and titanium tetraisopropoxide, furnished the corresponding alcohols in high enantioselectivities and in high yields.

Alkylative carbocyclization reactions of ω-iodoalkynyl tosylates with alkynyllithium compounds to give products with incorporated iodine atoms are described. Slow addition of 2-(3-iodoprop-2-ynyloxy)ethyl tosylates to 1-alkynyllithium compounds in tetrahydrofuran at 40 °C followed by additional stirring at this temperature gives (Z)-3-(1-iodoprop-2-ynylidene)tetrahydrofurans stereoselectively in good to moderate yields. Under similar conditions at 0 °C, 4-iodobut-1-ynyl tosylates react with 1-alkynyllithium compounds to give (1-iodoprop-2-ynylidene)cyclopropanes. The carbocyclization reactions are proposed to proceed through a new carbenoid-chain process involving the exo cyclization of a lithium acetylide intermediate and the vinylic substitution of the resulting TsO,Li-cycloalkylidenecarbenoids (Ts=tosyl) by 1-alkynyllithium compounds.

Enantioselective aldol addition to ketones has received growing attention since the resulting tertiary aldols are valuable building blocks for many biologically active compounds. Recently, several catalytic methodologies have been developed based on the activation of acceptor ketones and/or nucleophile enolates, overcoming problems associated with the lower reactivity and decreased steric discrimination of ketones compared to aldehydes. This microreview presents an overview of the progresses in the catalytic enantioselective aldol additions to ketones. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Triethylborane can be used in the asymmetric alkylation of aldehydes by using a 3-(3,5-diphenylphenyl)-H₈-BINOL-derived titanium(IV) catalyst in the presence of an excess amount of titanium tetraisopropoxide. The reaction proceeds with a low catalyst loading (2 mol-%), exhibiting high enantioselectivity for aromatic and unsaturated aldehydes. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)