Catalyst‐Controlled Regiodivergent Alkyne Insertion in the Context of C−H Activation and Diels–Alder Reactions: Synthesis of Fused and Bridged Cycles

• Published in: Angewandte Chemie International Edition Vol. 56; no. 28; pp. 8163 - 8167
• Main Authors: Zhou, Xukai, Pan, Yupeng, Li, Xingwei
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 03.07.2017; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Activation; Alkynes; Catalysis; Catalysts; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Cobalt; cycloadditions; C−H activation; Diels-Alder reactions; Indoles; Insertion; Physical Sciences; polycycles; Regioselectivity; Rhodium; Science & Technology; Selectivity; ONE-POT SYNTHESIS; ANNULATION; ARENES; TERMINAL ALKYNES; cobalt; cycloadditions; INTERNAL ALKYNES; ARYLATIVE CYCLIZATION; FUNCTIONALIZATION; C-H activation; N-TYPE REACTIONS; INDOLE SYNTHESIS; BOND ACTIVATION; polycycles; rhodium; C−H activation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201704036

Rhodium(III)‐ and cobalt(III)‐catalyzed C−H activation of indoles and coupling with 1,6‐enynes is discussed. Under rhodium(III) catalysis, the alkyne insertion follows 2,1‐regioselectivity with a subsequent type‐I intramolecular Diels–Alder reaction (IMDA) to afford [6,5]‐fused cycles. When catalyzed by the cobalt(III) congener, 1,2‐insertion of the alkyne is preferred, and followed by a rare type‐II IMDA, thus leading to bridged [3,3,1]‐cycles. This selectivity of the alkyne insertion was mainly tuned by the steric sensitivity of the catalyst. Divergent couplings of indoles with enynes have been realized under catalyst control. Under RhIII catalysis, fused cycles were obtained by an alkyne 2,1‐insertion/Diels–Alder sequence. In contrast, rare bridged cycles were obtained by a 1,2‐insertion/Diels–Alder sequence enabled by CoIII catalysis. The reaction conditions are mild and lead to a single diastereomer with more than four stereogenic centers.