Enantioselective Synthesis of Axially Chiral Biaryls by Diels–Alder/Retro-Diels–Alder Reaction of 2‑Pyrones with Alkynes

• Published in: Journal of the American Chemical Society Vol. 143; no. 24; pp. 8993 - 9001
• Main Authors: Xu, Meng-Meng, You, Xin-Yu, Zhang, Yu-Zhen, Lu, Yang, Tan, Kui, Yang, Limin, Cai, Quan
• Format: Journal Article
• Language: English
• Published: American Chemical Society 23-06-2021
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.1c04759

The enantio­selective synthesis of axially chiral biaryls by a copper-catalyzed Diels–Alder/retro-Diels–Alder reaction of 2-pyrones with alkynes is reported herein. Using electron-deficient 2-pyrones and electron-rich 1-naphthyl acetylenes as the reaction partners, a broad range of axially chiral biaryl esters are obtained in excellent yields (up to 97% yield) and enantio­selectivities (up to >99% ee). DFT calculations reveal the reaction mechanism and provide insights into the origins of the stereo­selectivities. The practicality and robustness of this reaction are showcased by gram-scale synthesis. The synthetic utilizations are demonstrated by the amenable transformations of the products.