Accessing Unsymmetrically Linked Heterocycles through Stereoselective Palladium‐Catalyzed Domino Cyclization

• Published in: Angewandte Chemie International Edition Vol. 61; no. 1; pp. e202112288 - n/a
• Main Authors: Arora, Ramon, Rodríguez, José F., Whyte, Andrew, Lautens, Mark
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 03.01.2022; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkenes; Alkynes; Catalysts; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; cyclization; heterocycles; Nucleophiles; Palladium; Physical Sciences; Science & Technology; Stereoselectivity; synthetic methods; BIS(INDOLYL)METHANE; ALKYLATION; EFFICIENT SYNTHESIS; OXINDOLES; ALKYNES; cyclization; C-H ACTIVATION; SPIROOXINDOLES; stereoselectivity; heterocycles; SEQUENCE; palladium; ARYL; DERIVATIVES; synthetic methods
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202112288

A palladium‐catalyzed strategy is presented to synthesize unsymmetrically linked heterocycles within stereoselective tetrasubstituted olefins. This reaction is proposed to occur via a vinyl‐PdII intermediate capable of initiating the cyclization of various alkyne‐tethered nucleophiles. Products are formed in up to 96 % yield and excellent stereoselectivities are obtained using low catalyst loadings. This transformation was scalable up to 1 mmol and mechanistic studies suggest a syn‐carbopalladation of the carbamoyl chloride followed by PdII‐catalyzed cyclization of alkyne‐tethered nucleophiles. Solving alkynes of problems with palladium. A palladium‐catalyzed domino cyclization of alkyne‐tethered carbamoyl chlorides and aryl iodides with alkyne‐tethered aryl nucleophiles is reported. This methodology unsymmetrically links heterocycles along a tetrasubstituted olefin with >20:1 E/Z selectivity and up to 96 % yield.