Synthesis of Unsymmetrically Substituted Bipyridines by Palladium-Catalyzed Direct C−H Arylation of Pyridine N-Oxides

Abstract

Substituted bipyridines were efficiently prepared by direct coupling between pyridine N-oxides and halopyridines using a palladium catalyst. Pyridine N-oxides with electron-withdrawing substituents gave the best yields. This method allows the convenient preparation of 2,2'-, 2,3'-, and 2,4'-bipyridines which are useful as functionalized ligands for metal complexes or as building blocks for supramolecular architectures.

Cross‐Coupling of Heteroarenes by CH Functionalization: Recent Progress towards Direct Arylation and Heteroarylation Reactions Involving Heteroarenes Containing One Heteroatom

“…3 -catalyzed C-2 arylation of compounds 283 with 3-bromopyridines. [189] Bipyridine N-oxides were also obtained in moderate to good yields from pyridine N-oxides with electron-withdrawing substituents in the 4-position and 2-bromopyridines [189] and this result was consistent with a previous report that pyridine N-oxides bearing electron-withdrawing substituents are significantly more reactive than pyridine N-oxides with electrondonating substituents.…”

“…[188] Again in 2011, Duric and Tzschucke synthesized 2,2'-, 2,3'-and 2,4'-bipyridine N-oxides 284 from pyridine N-oxides 283 and bromopyridines [189] (Scheme 147) using a protocol very similar to that developed by Fagnou and co-workers for the synthesis of 6-arylpyridine N-oxides 262. [180] Compounds 284 were then deoxygenated to give bipyridines 285 (Scheme 147).…”

“…[180] Compounds 284 were then deoxygenated to give bipyridines 285 (Scheme 147). [189] This protocol allowed the authors to obtain compounds 284 in moderate to good yields but in many cases significant amounts of terpyridine N-oxides 286 ( Figure 39) were also obtained. [189] The best yields of compounds 284 were obtained when pyridine Noxides 283 bearing electron-withdrawing substituents were employed as substrates.…”

Biaryl Synthesis through Metal‐Catalyzed C–H Arylation

“…In 2009, You [80] also reported a similar copper-catalyzed C-H coupling, and Fagnou [126c] improved his previous used reaction conditions to allow for using aryl triflates as coupling partner. In 2011, Tzschucke [128] applied an azole N-oxide coupling to the synthesis of 2,2 -bipyridines.…”

Transition-Metal-Catalyzed Functionalization of Pyridines

“…2011 年德国生物化学与化学研究所的 Tzschucke 等 [24] 报道了氧化吡啶和溴代吡啶在 Pd(OAc) 2 催化下发 2007 年美国伊利诺伊大学香槟分校的 Hartwig 等 [41] 报道了[Ir(cod)(OMe)] 2 催化下吡啶的间位卤化, 经历的 中间体是吡啶间位硼基化产物(Scheme 18). (mono 45%, di: 31%) R = CH 2 SiMe 3 : (mono: 40%) 48% (39) 2010 年 Nakao 和 Hiyama 等 [50] 报道了 Ni(cod) 2 催化 的吡啶对位烷基化, 主要生成直链烷基化产物, 只有吡 啶和苯乙烯反应主要生成支链烷基化产物(Eq.…”