2‐Hydroxypyridines as N‐ and O‐Nucleophiles in Organic Synthesis

Abstract

2‐Hydroxypyridines have emerged as versatile nucleophiles in organic synthesis. The N‐ and O‐functionalization of 2‐hydroxypyridines affords straightforward and practical methods for the construction of N‐substituted 2‐pyridones and O‐substituted 2‐hydroxypyridines, which are important structural motifs in numerous natural products, pharmaceuticals and biologically active compounds. Nonetheless, the competition between N‐ and O‐functionalization of 2‐hydroxypyridines presents an inevitable and formidable challenge. In the past few decades, chemoselective N‐ and/or O‐functionalization of 2‐hydroxypyridines has received extensive attention from the synthetic community, resulting in the development of elegant and effective strategies to address this chemoselectivity. This review provides a summary of recent advancements in the realm of transition‐metal and organo‐catalyzed, as well as visible‐light promoted chemoselective functionalization of 2‐hydroxypyridines, including N‐alkylation, N‐allylation, N‐arylation, N‐alkenylation, O‐alkylation, O‐allylation, O‐arylation, and O‐alkenylation.

Gold(i)-catalyzed synthesis of N-alkenyl 2-pyridonyl sec-amines

“…1 Therefore, the development of various synthetic methods to obtain this compound and its derivatives has become of great importance for organic chemists. 2 A cyclization reaction, with or without metals, is one way to produce N -alkylated 2-pyridones, which are starting materials devoid of pyridine and pyridone rings. 3 In addition to these techniques, methods such as migration, alkylation, addition, and rearrangement of the derivatives of pyridine and pyridone are commonly used to produce this skeleton.…”