Catalytic asymmetric indolization by a desymmetrizing 3 + 2 annulation strategy

• Published in: Chemical science (Cambridge) 2023-07, Vol.14 (29), p.7980
• Main Authors: Wu, Changhui, Chang, Zhiqian, Peng, Chuanyong, Bai, Chen, Xing, Junhao, Dou, Xiaowei
• Format: Article
• Language: English
• ISSN: 2041-6520
• DOI: 10.1039/d3sc02474a

A new catalytic asymmetric indolization reaction by a desymmetrizing [3 + 2] annulation strategy is developed. The reaction proceeds via a rhodium-catalyzed enantioposition-selective addition/5-exo-trig cyclization/dehydration cascade between ortho-amino arylboronic acids and 2,2-disubstituted cyclopentene-1,3-diones to produce N-unprotected cyclopenta[b]indoles bearing an all-carbon quaternary stereocenter in high yields with good enantioselectivities. A quantitative structure-selectivity relationship (QSSR) model was established to identify the optimal chiral ligand, which effectively controlled the formation of the stereocenter away from the reaction site. Density functional theory (DFT) calculations, non-covalent interaction analysis, and Eyring analysis were performed to understand the key reaction step and the function of the ligand.A new catalytic asymmetric indolization reaction by a desymmetrizing [3 + 2] annulation strategy is developed. The reaction proceeds via a rhodium-catalyzed enantioposition-selective addition/5-exo-trig cyclization/dehydration cascade between ortho-amino arylboronic acids and 2,2-disubstituted cyclopentene-1,3-diones to produce N-unprotected cyclopenta[b]indoles bearing an all-carbon quaternary stereocenter in high yields with good enantioselectivities. A quantitative structure-selectivity relationship (QSSR) model was established to identify the optimal chiral ligand, which effectively controlled the formation of the stereocenter away from the reaction site. Density functional theory (DFT) calculations, non-covalent interaction analysis, and Eyring analysis were performed to understand the key reaction step and the function of the ligand.