Chemoselective and Diastereoselective Synthesis of <i>C</i>‐Aryl Nucleoside Analogues by Nickel‐Catalyzed Cross‐Coupling of Furanosyl Acetates with Aryl Iodides
Yuxi Li, Zheng Wang, Luyang Li, Xiaoying Tian, Feng Shao, Chao Li
Abstract
Canonical nucleosides are vulnerable to enzymatic and chemical degradation, yet their stable mimics-C-aryl nucleosides-have demonstrated potential utility in medicinal chemistry, chemical biology, and synthetic biology, although current synthetic methods remain limited in terms of scope and selectivity. Herein, we report a cross-electrophile coupling to prepare C-aryl nucleoside analogues from readily available furanosyl acetates and aryl iodides. This nickel-catalyzed modular approach is characterized by mild reaction conditions, broad substrate scope, excellent β-selectivity, and high functional-group compatibility. The exclusive chemoselectivity with respect to the aryl iodide enables efficient preparation of a variety of C-aryl halide furanosides suitable for various downstream transformations. The practicality of this transformation is demonstrated through the synthesis of a potent analogue of a naturally occurring NF-κB activator.