Copper‐Catalyzed Azide–Ynamide Cyclization to Generate α‐Imino Copper Carbenes: Divergent and Enantioselective Access to Polycyclic N‐Heterocycles

• Published in: Angewandte Chemie International Edition Vol. 59; no. 41; pp. 17984 - 17990
• Main Authors: Liu, Xin, Wang, Ze‐Shu, Zhai, Tong‐Yi, Luo, Chen, Zhang, Yi‐Ping, Chen, Yang‐Bo, Deng, Chao, Liu, Rai‐Shung, Ye, Long‐Wu
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 05.10.2020; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkynes; asymmetric catalysis; Asymmetry; Carbenes; Catalysts; Chemistry; Chemistry, Multidisciplinary; Copper; cyclizations; Divergence; Enantiomers; heterocycles; Intermediates; Physical Sciences; Science & Technology; Substrates; 2H-AZIRINES; TETHERED ALKYNES; C-H ANNULATION; alkynes; EFFICIENT SYNTHESIS; RAPID ACCESS; asymmetric catalysis; 2-ALKYNYL ARYLAZIDES; CASCADE REACTION; NUCLEOPHILIC NITRENOIDS; cyclizations; CYCLOADDITION; heterocycles; copper; OXO GOLD CARBENES
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202007206

Here an efficient copper‐catalyzed cascade cyclization of azide‐ynamides via α‐imino copper carbene intermediates is reported, representing the first generation of α‐imino copper carbenes from alkynes. This protocol enables the practical and divergent synthesis of an array of polycyclic N‐heterocycles in generally good to excellent yields with broad substrate scope and excellent diastereoselectivities. Moreover, an asymmetric azide–ynamide cyclization has been achieved with high enantioselectivities (up to 98:2 e.r.) by employing BOX‐Cu complexes as chiral catalysts. Thus, this protocol constitutes the first example of an asymmetric azide–alkyne cyclization. The proposed mechanistic rationale for this cascade cyclization is further supported by theoretical calculations. An efficient copper‐catalyzed cascade cyclization of azide‐ynamides via α‐imino copper carbene intermediates is disclosed, enabling divergent synthesis of polycyclic N‐heterocycles in generally good to excellent yields with broad substrate scope and excellent diastereoselectivities, representing the first generation of α‐imino copper carbenes directly from alkynes. The asymmetric azide–ynamide cyclization has been achieved with high enantioselectivities.