Synthesis Of Sulfonamide Alcohols And Application In The Enantioselective Addition Of Alkynylzinc To Aldehydes And Ketones

Catalytic asymmetric reactions are among the most important organic reactions, which create good fortunes to enantiomerically pure chiral drugs and other materials, and continue to be one of the most studied and important areas in organic chemistry. Optically active propargyl alcohols are important and versatile building blocks for the synthesis of a wide range of Pharmaceuticals and natural products. The enantioselective alkynylzinc addition to carbonyl compounds is very useful for the synthesis of chiral propargyl alcohols and has gained considerable significance in recent years. Herein we mainly discuss design and synthesis of some novel chiral ligands or catalysts and their application to the asymmetric addition of alkynylzinc to aldehydes and ketones.a) From commercially available natural L-phenylalanine, novel C2-symmetrical bissulfonamide ligands 56-57 were easily prepared in three simple steps and applied in the enantioselective addition of alkynylzinc reagents to aldehydes. Ligand 56 was found to be an outstanding ligand for this reaction. High enantioselectivity with an ee value up to 97% was achieved under very mild conditions.b) By the same routine, novel C2-symmetrical bissulfonamide ligands 56-57 were easily prepared, which were applied in the enantioselective addition of alkynylzinc to ketones in the presence of Ti(O-i-Pr)₄. Ligand 56 in combination with Ti(O-i-Pr)₄ was found to be effective in promoting the addition reaction of an alkynylzinc reagent to unactivated simple ketones under very mild conditions. The corresponding chiral tertiary propargylic alcohols were obtained with enantiomeric excesses of up to 81%.c) Starting from natural amino acides, we conveniently prepared ligands 60a-e and applied them in the enantioselective addition of phenylacetylene to ketones. p-sulfonamide alcohol 60b in combination with Ti(O-i-Pr)₄ was found to be effective in promoting the addition reaction of an alkynylzinc reagent to unactivated simple ketones under very mild conditions. The correspondingchiral tertiary propargylic alcohols were obtained with enantiomeric excesses ofupto80%.d) Starting from natural (+)-camphor, P-sulfonamide alcohol 65 was conveniently prepared and applied in the enantioselective addition of phenylacetylene to ketones. P-sulfonamide alcohol 65 in combination with Ti(O-i-Pr)4 was found to be effective in promoting the addition reaction of an alkynylzinc reagent to unactivated simple ketones under very mild conditions. The corresponding chiral tertiary propargylic alcohols were obtained with enantiomeric excesses ofupto86%.