Generation of Donor/Donor Copper Carbenes through Copper-Catalyzed Diyne Cyclization: Enantioselective and Divergent Synthesis of Chiral Polycyclic Pyrroles

• Published in: Journal of the American Chemical Society Vol. 141; no. 42; pp. 16961 - 16970
• Main Authors: Hong, Feng-Lin, Wang, Ze-Shu, Wei, Dong-Dong, Zhai, Tong-Yi, Deng, Guo-Cheng, Lu, Xin, Liu, Rai-Shung, Ye, Long-Wu
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 23.10.2019; Amer Chemical Soc
• Subjects: alkynes; carbenes; catalysts; catalytic activity; Chemistry; Chemistry, Multidisciplinary; cyclization reactions; enantioselectivity; gold; Physical Sciences; pyrroles; Science & Technology; REARRANGEMENT; INSERTION; ACTIVATION; DUAL GOLD CATALYSIS; C-H ANNULATION; RAPID ACCESS; CYCLOISOMERIZATION; CASCADE CYCLIZATION; 2+2+2 CYCLOADDITION; ALKYNES
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.9b09303

The generation of metal carbenes from readily available alkynes represents a significant advance in metal carbene chemistry. However, most of these transformations are based on the use of noble-metal catalysts and successful examples of such an asymmetric version are still very scarce. Here a copper-catalyzed enantioselective cascade cyclization of N-propargyl ynamides is reported, enabling the practical and atom-economical construction of diverse chiral polycyclic pyrroles in generally good to excellent yields with wide substrate scope and excellent enantioselectivities (up to 97:3 e.r.). Importantly, this protocol represents the first copper-catalyzed asymmetric diyne cyclization. Moreover, mechanistic studies revealed that the generation of donor/donor copper carbenes is presumably involved in this 1,5-diyne cyclization, which is distinctively different from the related gold catalysis, and thus it constitutes a novel way for the generation of donor/donor metal carbenes.