Design, development and applications of copper-catalyzed regioselective (4 + 2) annulations between diaryliodonium salts and alkynes

• Published in: Communications chemistry Vol. 5; no. 1; p. 145
• Main Authors: Wang, Weilin, Zhou, Junrui, Wang, Chao, Zhang, Congdi, Zhang, Xiao-Qian, Wang, Youliang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/403/977; Alkenes; Alkynes; Aromatic compounds; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Copper; Cycloaddition; Dipoles; Natural products; Regioselectivity; Stoichiometry; Transition metals
• ISSN: 2399-3669; 2399-3669
• DOI: 10.1038/s42004-022-00768-3

Diaryliodonium salts have been extensively applied in organic synthesis as aryl cation equivalents. However, in the electrophilic reactions with alkenes or alkynes, only the electrophilic carbon of the diaryliodonium salts was involved while the other part of the aryl ring was not utilized. Herein, a reaction pattern of diaryliodonium was reported as oxa-1,4-dipoles to undergo (4 + 2) cycloaddition reactions with alkynes. Broad spectrum of the two reaction partners could be utilized in this protocol, enabling an operationally simple, high yielding, and regioselective synthetic approach to isocoumarins. Particularly, good to excellent regioselectivities were achieved for the sterically unbiased unsymmetrical diaryl acetylenes, which was challenging for other transition metal-catalyzed processes. The reaction could be scaled up with the ideal 1:1 stoichiometry and the isocoumarin type natural products Oospolactone and Thunberginol A could be obtained in one or three steps through this methodology. Intermolecular (4 + 2) cycloaddition with alkynes is a powerful approach to construct isocoumarin moieties, however, regioselectivity remains challenging for the transition metal-catalyzed approach. Here, the authors report copper-catalyzed regioselective (4 + 2) annulations between diaryliodonium salts and alkynes to synthesize isocoumarin-type natural products.