Chiral aldehyde-nickel dual catalysis enables asymmetric α−propargylation of amino acids and stereodivergent synthesis of NP25302

• Published in: Nature communications Vol. 13; no. 1; pp. 7290 - 9
• Main Authors: Zhu, Fang, Li, Chao-Xing, Wu, Zhu-Lian, Cai, Tian, Wen, Wei, Guo, Qi-Xiang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/77/883; Alcohol; Aldehydes; Aldehydes - chemistry; Amino acids; Amino Acids - chemistry; Asymmetry; Catalysis; Chemical synthesis; Chemistry; Esters; Heavy metals; Humanities and Social Sciences; Laboratories; Ligands; Metals; multidisciplinary; Natural products; Nickel; Nonlinear control; Palladium; Reaction mechanisms; Science; Science (multidisciplinary); Selectivity; Stereoisomerism; Stereoselectivity; Transition metals
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35062-2

The combined catalytic systems derived from organocatalysts and transition metals exhibit powerful activation and stereoselective-control abilities in asymmetric catalysis. This work describes a highly efficient chiral aldehyde-nickel dual catalytic system and its application for the direct asymmetric α−propargylation reaction of amino acid esters with propargylic alcohol derivatives. Various structural diversity α,α−disubstituted non-proteinogenic α−amino acid esters are produced in good-to-excellent yields and enantioselectivities. Furthermore, a stereodivergent synthesis of natural product NP25302 is achieved, and a reasonable reaction mechanism is proposed to illustrate the observed stereoselectivity based on the results of control experiments, nonlinear effect investigation, and HRMS detection. The combination of transition metal catalysis and organocatalysis can afford both good reactivity and selectivity. Here, the authors present an α − propargylation of N-unprotected amino acid esters with propargylic alcohol derivatives via dual nickel and chiral aldehyde catalysis.