Asymmetric dearomatization catalysed by chiral Brønsted acids via activation of ynamides

• Published in: Nature chemistry Vol. 13; no. 11; pp. 1093 - 1100
• Main Authors: Zhang, Ying-Qi, Chen, Yang-Bo, Liu, Ji-Ren, Wu, Shao-Qi, Fan, Xin-Yang, Zhang, Zhi-Xin, Hong, Xin, Ye, Long-Wu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2021; NATURE PORTFOLIO; Nature Publishing Group
• Subjects: 639/638/403/933; 639/638/403/934; 639/638/549/933; 639/638/77/883; Acids; Alkynes; Analytical Chemistry; Asymmetric synthesis; Asymmetry; Biochemistry; Carbon; Carbonyl compounds; Carbonyls; Catalysis; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemistry, Multidisciplinary; Chemistry/Food Science; Inorganic Chemistry; Naphthol; Organic Chemistry; Phenols; Physical Chemistry; Physical Sciences; Pyrroles; Science & Technology; PHENOL; CONSTRUCTION; METAL CATALYSIS
• ISSN: 1755-4330; 1755-4349; 1755-4349
• DOI: 10.1038/s41557-021-00778-z

Chiral Brønsted acid-catalysed asymmetric synthesis has received tremendous interest over the past decades, and numerous efficient synthetic methods have been developed based on this approach. However, the use of chiral Brønsted acids in these reactions is mostly limited to the activation of imine and carbonyl moieties, and the direct activation of carbon–carbon triple bonds has so far not been invoked. Here we show that chiral Brønsted acids enable the catalytic asymmetric dearomatization reactions of naphthol-, phenol- and pyrrole-ynamides by the direct activation of alkynes. This method leads to the practical and atom-economic construction of various valuable spirocyclic enones and 2H-pyrroles that bear a chiral quaternary carbon stereocentre in generally good-to-excellent yields with excellent chemo-, regio- and enantioselectivities. The activation mode of chiral Brønsted acid catalysis revealed in this study is expected to be of broad utility in catalytic asymmetric reactions that involve ynamides and the related heteroatom-substituted alkynes. Chiral Brønsted acid catalysis is mostly limited to the activation of imine and carbonyl moieties. Now, by direct activation of alkynes, chiral Brønsted acids have been used to enable the catalytic asymmetric dearomatization of naphthol-, phenol- and pyrrole-ynamides for the construction of various spirocyclic enones and 2H-pyrroles bearing a chiral quaternary carbon stereocentre.