Enhancement of the Catalytic Activity of Chiral H8 -BINOL Titanium Complexes by Introduction of Sterically Demanding Groups at the 3-Position.

The activity of chiral titanium catalysts derived from H8 -BINOL ligands in the enantioselective arylation of an aldehyde with PhTi(OiPr)3 is significantly enhanced by an increase of the size of the substituent at the 3-position. High enantioselectivity (> 90 % ee) can be obtained even at a substrate/catalyst ratio (S/C) of 800 for DTBP-H8 -BINOL (DTBP=3,5-di-tert-butylphenyl) and DAP-H8 -BINOL (DAP=3,5-di(9-anthraceny)phenyl). These titanium catalysts are successfully applied to the enantioselective arylation and heteroarylation of aldehydes at a S/C ratio of 400 by using organotitanium reagents generated in situ from bromide precursors. The remarkable weakening of the intramolecular aggregation of the two -Ti(OiPr)3 units in a DPP-H8 -BINOL (DPP=3,5-diphenylpheny)-derived bis-titanium complex is revealed by X-ray and variable-temperature (VT)-NMR studies. Based on these observations, a catalytic cycle, involving the rate-limiting aryl group transfer followed by aldehyde complexation and enantioselective arylation, is proposed to account for the high activity of the 3-substituted H8 -BINOL catalyst system.

Catalytic enantioselective alkylation of aldehydes by using organozinc halide reagents.

Functionalized alkylzinc halides can be employed in the enantioselective addition to aldehydes by using a titanium(IV) catalyst derived from a H(8)-binaphthol derivative in the presence of [Ti(OiPr)(4)] and MgBr(2). A range of functionalities, including olefin, chlorine atoms, protected alcohols, amides, and cyano groups, are tolerated in the present reaction, providing the corresponding functionalized alcohols in high yields and enantioselectivities (see scheme).