Catalytic Alkynylation Of Aldehydes And Ketones Using Natural Amino Acid Derived Chiral Ligands

Catalysis is an essential technology supporting our way of life and catalytic asymmetric reactions are among the most important organic reactions. Energy efficient chemical transformations, environmental protection, and green chemistry will rely heavily on catalysis. The Asymmetric addition of terminal alkynes to aldehydes and ketones is an important method of synthesizing chiral propartyl alcohols and tertiary alcohols, which are important pharmaceutical intermediates. Herein we mainly discuss design and synthesis of some novel chiral ligands or catalysts which derived from natural amino acids and their application to the asymmetric addition of terminal alkynes to aldehydes and ketones.(1) Some simple derivatives of natural amino acids were successfully used as chiral ligands in the catalytic asymmetric addition of phenylacetylene to aldehydes. The reactions with derivatives of proline were more enantioselective on account of its special structure. Ligand 1c, derived from L-proline, showed the highest enantioselectivity with 90% ee.(2) Simple derivatives of L-leucine 3a-3i were successfully used as chiral ligands in the catalytic asymmetric addition of phenylacetylene to aldehydes. Ligand 3b gave higher enantioselectivity (up to 96% ee) and chemical yield. The results showed that the R group of the a -carbon greatly influenced the enantioselectivity.(3) Ligands 1a-6a could be conveniently synthesized from cheap chiral resources (S)-phenylglycine, (S)-valine, (S)-tyrosine, (S)-tryptophan and (S)-proline in two steps. When we used ligand 4a in the asymmetric addition of phenylacetylene to aldehydes at room temperature, the highest ee was up to 99%. The conditions of this catalytic process are both mild and simple. The results disclosed the backbone of the ligands could affect the enantioselectivity of this reaction.(4) Novel tridentate ligands 2a-2d have been prepared from commercially available L-threonine ester in only one step. When compound 2a was used as ligand in combination with Ti(O'Pr)4 in the reaction of phenylacetylene addition to aromatic ketones, the results obtained are quite promising in terms of yields and enantiomeric excess (up to 83% ee).