Lewis Acidity Of Titanium Complex Affected The Enatioselective Addition Of Alkyne To Aldehydes Reaction In Non-protonic Solvents

The N-H group of sulfonamide is acidic. Unlike traditional metal amides (MNR 2), the nitrogen atom of sulfonamide is a poor electron donor and the N-H group of the sulfonamide-Ti complex is a Lewis acid, owing to the highly electron-withdrawing nature of the sulfonyl group. Amino alcohols derived from natural amino acids are among the best and the most economical chiral ligands available. We introduced the sulfonyl group to P-amino alcohols derived from amino acids to prepare β-sulfonamide alcohols. As a result of the presence of acidic N-H and O-H groups, the titanium complex was readily formed from these compounds when they were combined with Ti(OⁱPr)₄ under basic conditions. Initially, we expected these complexes to be similar as BINOL-Ti complexes, and that they could be straightforwardly applied to the enantioselective addition of phenylacetylene to aldehydes. To our astonishment, this kind of titanium complex had a very different catalytic activity from the BINOL-Ti complex in this type of reaction. The separate step to prepare the zinc-acetylide by combining ZnEt2 and alkyne at high temperature was not required. After the conditions had been optimized, these ligands could efficiently catalyze the asymmetric alkynylation of aldehydes with high ees and high yields in one step. When the conditions were optimized, exploring 20mol% of ligand 8a could catalyze the reaction with high enantioselectivity (up to 98% ee) and good yield (up to 92%). When small amount of MeOH was added to the reaction as a modifier, the loading of the ligand could decrease to 5mol% under very mild conditions, resulting the ee values up to 99% with good yields.