Tandem Cross‐Coupling/Spirocyclization/Mannich‐Type Reactions of 3‐(2‐Isocyanoethyl)indoles with Diazo Compounds toward Polycyclic Spiroindolines

• Published in: Angewandte Chemie International Edition Vol. 59; no. 2; pp. 614 - 621
• Main Authors: Chen, Guo‐Shu, Chen, Shu‐Jie, Luo, Jian, Mao, Xiang‐Yu, Chan, Albert Sun‐Chi, Sun, Raymond Wai‐Yin, Liu, Yun‐Lin
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 07.01.2020; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkaloids; asymmetric synthesis; Cascade chemical reactions; Chemical reactions; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Coupling (molecular); Cross coupling; diazo compounds; Indoles; Organic chemistry; Phosphoric acid; Physical Sciences; polycyclic spiroindolines; Science & Technology; spirocyclization; NATURAL-PRODUCTS; CATALYTIC ASYMMETRIC DEAROMATIZATION; FORMAL TOTAL-SYNTHESIS; VERSATILE BUILDING-BLOCKS; MULTICOMPONENT REACTIONS; asymmetric synthesis; polycyclic spiroindolines; RADICAL CYCLIZATIONS; cross-coupling; spirocyclization; GENERAL SYNTHETIC PATHWAY; diazo compounds; STRYCHNOS INDOLE ALKALOIDS; ENANTIOSELECTIVE TOTAL-SYNTHESIS; ASPIDOSPERMA ALKALOIDS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201911614

Tandem reactions of Pd‐catalyzed cross‐coupling of 3‐(2‐isocyanoethyl)indoles with diazoacetates and subsequent spirocyclization/Mannich‐type reaction have been developed to assemble polycyclic spiroindoline skeletons. Formation of spiroindolenines has been proven as the crucial step for the following Mannich‐type cyclization reaction. Accordingly, a novel approach on chiral phosphoric acid catalyzed Mannich‐type cyclization toward the formation of diastereomerically and enantiomerically enriched pentacyclic spiroindolines has been established. Moreover, the products of the reaction are versatile building blocks in synthetic chemistry, as demonstrated by the synthesis of the key framework of aspidosperma and kopsia alkaloids. Polycyclic spiroindoline skeletons can be constructed through Pd‐catalyzed cross‐coupling of 3‐(2‐isocyanoethyl)indoles with diazoacetates and a subsequent spirocyclization/Mannich‐type cyclization cascade reaction. The products are versatile building blocks in synthetic chemistry, as demonstrated by the synthesis of the key framework of aspidosperma and kopsia alkaloids.