2,2′‐Homocoupled Azine N,N′‐Dioxides or Azine N‐Oxides: CDC‐ or S_NAr‐Controlled Chemoselectivity

Abstract

An unprecedented Cu(OAc)2‐ and LiOtBu‐mediated homocoupling of azine N‐oxides to yield 2,2′‐azine N,N′‐dioxides is reported. This is the first instance in which copper has been used to catalyze the homodimerization reaction, especially of 2‐phenylpyridine N‐oxides. In the absence of catalytic copper, the reaction follows an alternative pathway, and instead of dioxides it yields 2,2′‐azine N‐monoxides. This latter protocol works efficiently with a range of N‐heterocyclic oxides of pyridine, 2‐phenylpyridine, quinoline and N‐aryl‐1,2,3‐triazole. It is scalable, offers high regioselectivity and gives the products in moderate to high yields. The observed chemoselectivity between the copper‐assisted and copper‐free protocols is routed through oxidative cross‐dehydrogenative coupling (CDC) and nucleophilic aromatic substitution of hydrogen (SNAr) pathways, respectively.

Recent Advances in the Synthesis of 2,2′-Bipyridines and Their Derivatives

“…It later received a number of useful synthetic modifications to broaden the scope, 51 including its applica-tion for the synthesis of axially chiral derivatives. 52 In one of the most recent examples, Wang et al reported the synthesis of a highly substituted bipyridine 44 from 2-cyanopyridine (42) and diphenylacetylene (43) using a catalytic system consisting of cobalt(II) iodide, dppe and Zn in NMP (Scheme 24). 53 Scheme 24 Synthesis of bipyridines by cyclotrimerization of 2-cyanopyridine and diphenylacetylene; dppp = 1,3-bis(diphenylphosphino)propane; NMP = N-methyl-2-pyrrolidine An alternative method for the synthesis of 2,2′-bipyridine derivatives was described by Khlebnikov (Scheme 25).…”

The 2‐Pyridyl Problem: Challenging Nucleophiles in Cross‐Coupling Arylations

“…AP d-free homocoupling of pyridine N-oxide was developed through the use of as trong base (Scheme 37). [149] Depending on whether or not copper acetate was added, the reaction would go through two different pathways:S N Ar (although it might be ar adical addition [150] )o racoppercatalysed oxidative coupling.While both pathways enable the homocoupling,t he S N Ar pathwaysf inal deoxygenative rearomatisation step produces an N-oxide rather than the N,N'dioxide.…”

Advances in C(sp2)−H/C(sp2)−H Oxidative Coupling of (Hetero)arenes Using 3d Transition Metal Catalysts

“…Jain and co‐workers have extended the copper‐catalyzed homocoupling strategy to the oxidative coupling of azine N ‐oxides resulting in 2,2’‐azine N,N’ ‐dioxides (Scheme 49). [93] Thus, the Cu(OAc) 2 /LiO t Bu system efficiently catalyzed the oxidative coupling of various N ‐heterocyclic oxides of pyridine. Initial deprotonation of pyridine N ‐oxide by LiO t Bu generates a lithium salt, which undergoes transmetalation with copper.…”