Pd-Catalyzed Aerobic Oxidative Heck Cross-Coupling for the Straightforward Construction of Indole δ-Lactams

• Published in: iScience Vol. 17; pp. 256 - 266
• Main Authors: Zhang, Jing, Han, Fu-She
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.07.2019; Elsevier
• Subjects: Catalysis; Chemistry; Organic Chemistry; Chemistry; Catalysis; Organic Chemistry
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2019.06.037

The [6.5.6]-tricyclic indole δ-lactam represents a common key intermediate for the synthesis of a broad variety of structurally intriguing indole alkaloids. The development of a method for the versatile and straightforward construction of such structural motif is of great importance for potential synthetic applications. Herein, we present a co-ligand-prompted Pd-catalyzed 6-exo-trig intramolecular cyclization of indolyl amides via the aerobic oxidative Heck cross-coupling. The method provided a general and efficient way for the construction of [6.5.6]-tricyclic indole δ-lactams. A mechanistic study suggests that a Pd(I)/Pd(III) catalytic cycle should be responsible for effective coupling, which represents a mechanistically alternative pathway when compared with the Pd(0)/Pd(II) cycle proposed for other related coupling reactions. [Display omitted] •Construction of indole δ-lactams enabled by a Pd-catalyzed oxidative Heck coupling•The phosphinamide L5 was crucial as a co-ligand for prompting the reaction•A Pd(I)/Pd(III) catalytic cycle is proposed to be responsible Catalysis; Chemistry; Organic Chemistry