Novel non-azacyclo 1,2-aminoalcohols derived from l-Phe and highly enantioselective addition of diethylzinc to aryl aldehydes

A series of non-azacyclo β-aminoalcohols derived from natural l-phenylalanine were readily synthesized in three steps. They were used as chiral ligands in the catalytic asymmetric addition of diethylzinc to aldehydes. The results showed that ligands with diethyl or dipropyl substituents on the carbinol carbons of the aminoalcohols favored higher enantioselectivities, and ligands with N,N-dimethyl groups gave better asymmetric induction than other N,N-dialkyl substituted ligands. Compound 5b was the most optimal ligand among these aminoalcohols, allowing to obtain a 96% ee. The results showed that high enantioselection should be determined by the subtle combination of the carbinol parts and amino parts of the aminoalcohols.

Graphical abstractNine novel non-azacyclo β-aminoalcohols were readily synthesized from natural l-phenylalanine in three straightforward steps. They were used as chiral ligands in the catalytic asymmetric addition of diethylzinc to aldehydes. The results showed that ligands with diethyl or dipropyl substituents on the carbinol carbons of the aminoalcohols favored higher enantioselectivities, and ligands with N,N-dimethyl groups gave better asymmetric induction than other N,N-dialkyl substituted ligands. Compound 5b was the most optimal ligand among these aminoalcohols, and 96% ee was obtained. Figure optionsDownload full-size imageDownload as PowerPoint slide