Study On The Catalytic Asymmetric Addition Of Alkynylzinc Reagent To Aldehydes And Ketones Using Chiral Pool And Their Derivatives

Asymmetric catalysis is an essential technology of catalytic reaction field, 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. 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 the asymmetric addition of terminal alkynes to aldehydes and ketones using commercially available chiral pool and their derivatives.(1) Commercially available Boc-L-Pro and peptide derivatives were successfully used as chiral ligands in the catalytic asymmetric addition of phenylacetylene to aldehydes, thus expanding the utility of the simplest enzyme, proline, in asymmetric catalysis. The ees of products were up to 77% and the condition was simple and easy to control in asymmetric addition of phenylacetylene to aldehydes.(2) BINOL, commercially available chiral pool, was successfully used as a chiral ligand in the catalytic asymmetric addition of phenylacetylene to ketones, thus expanding the utility of cheap and readily available BINOL in asymmetric catalysis. When the ratio of BINOL/Ti(OⁱPr)₄ was 1:1, the Lewis acidity of complex (BINOLate)-Ti(OⁱPr)₂ (BINOL/Ti(OⁱPr)₄=1:1) was acidic enough to activate inert ketones and catalyze the reaction. The results were good to excellent and the ees of products were up to 92%. The condition of the asymmetric reaction was simple, easy to control and all reactions were processed at room temperature.(3) Ligands 3a-3k could be conveniently synthesized from cheap chiral resources (S)-phenylalanine, (S)-valine, (S)-alanine, (S)-tryptophan, (S)-phenylglycine, (S)-leucine, and (S)-tyrosine in three steps. When we used ligand 3k-Zinc in the asymmetric addition of phenylacetylene to ketones at room temperature, the highest ee was up to 85%. The conditions of this catalytic process were both mild and simple. The results disclosed chiral hydroxysulfonamide-zinc system was one of the projects of asymmetric addition reactions.