The Application Of Analogs Of Dipeptide In The Catalytic Asymmetric Addition Reaction

Optically active propargyl alcohols are important precursors for the synthesis of many organic compounds and important pharmaceutical intermediates. The enantioselective addition of organometallic reagents to ketones is recognized as one of the most effective methodsHerein we mainly discuss design and synthesis of some novel chiral ligands or catalysts and their application to the asymmetric addition of organozinc to ketones. The new type of ligand derived from N-terminal protected L-Phe-based dipeptides was found to be effective in catalyzing the enantioselective addition of phenylacetylene to aromatic ketones with up to 91 % ee. The reaction required no other metal to promote than Et₂Zn. The whole process was completed at room temperature and proceeded under very mild reaction conditions.1. The synthesis of ligands 4a-4fFrom commercially available starting materials L-amino acid, the new type of ligands 4a-4f was prepared in three simple steps. The amino acid methyl ester was prepared form amino acid with methanol. Then it was reacted with MgBrX or H₄AlLi, the product was the corresponding amino alcohol. The amino alcohol reacted with Cbz-N-Phe via the classical methods of DCC/HOBt. We can get the desired ligands 4a-4f.2. The application of ligands in the reaction of phenylacetylene to aromatic ketonesWe used the ligands 4a-4f in the catalytic asymmetric addition reaction of phenylene to ketones. The condition of reaction is easy. In the present of Et₂Zn(Et₂Zn was diluted with toluene, 1mmol/ml), we used dichloromethane (DCM) as solvent in the reaction, ligands 4a-4f were applied in asymmetric alkynylation of ketone.3. Results and discussionThe ligand of 4f was the best ligand in the a series of six ligands. Used 4f as ligands, the ee values were up to 90% while yields up to 90% were obtained. Under the same conditions, we also used ligands 4f in the addition of phenylacetylene to the aliphatic ketone: isopropyl methyl ketone. The enantioselectivity was found to be54% (yield 80%).