33421-22-6

Upstream product

• 694-59-7 pyridine N-oxide 
• 591-17-3 meta-bromotoluene 
• 504-29-0 2-aminopyridine 
• 15009-91-3 2-nitropyridine 
• 4373-61-9 2-(m-tolyl)pyridine 
• 108-88-3 toluene 

Relevant academic research and scientific papers

2,2′-Homocoupled Azine N,N′-Dioxides or Azine N-Oxides: CDC- or SNAr-Controlled Chemoselectivity

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.

Palladium-catalyzed regioselective benzylation-annulation of pyridine N -oxides with toluene derivatives via multiple c-h bond activations: Benzylation versus arylation

A palladium-catalyzed cross-dehydrogenative coupling (CDC) reaction of pyridine N-oxides with toluenes has been developed that operates under mild conditions. 2-Benzylpyridines can be obtained directly by this method via a CDC reaction between unactivated toluenes and pyridine N-oxides. In addition, azafluorene N-oxides, of value for future medicinal chemistry applications, can be obtained successfully by this procedure via four tandem C-H bond activations.

Mechanistic studies on direct arylation of pyridine N -oxide: Evidence for cooperative catalysis between two distinct palladium centers

Direct arylations of pyridine N-oxide (PyO), a convenient method to prepare 2-arylpyridines, catalyzed by Pd(OAc)2 and PtBu3 have been proposed to occur by the generation of a PtBu3-ligated arylpalladium acetate complex, (PtBu3)Pd(Ar)(OAc) (1), and the reaction of this complex with PyO. We provide strong evidence that 1 does not react directly with PyO. Instead, our data imply that the cyclometalated complex [Pd(OAc)(tBu2PCMe2CH2)]2, which is generated from the decomposition of 1, reacts with PyO and serves as a catalyst for the reaction of PyO with 1. The reaction of PyO with 1 occurs with an induction period, and the reaction of 1 with excess PyO in the presence of [Pd(OAc)(tBu2PCMe2CH2)]2 is zeroth-order in 1. Moreover, the rates of reactions of PyO with bromobenzene catalyzed by [Pd(OAc)(tBu2PCMe2CH2)] 2 and [Pd(PtBu3)2] depend on the concentration of [Pd(OAc)(tBu2PCMe2CH2)]2 but not on the concentration of [Pd(PtBu3)2]. Finally, the reaction of 1 with a model heteroarylpalladium complex containing a cyclometalated phosphine, [(PEt3)Pd(2-benzothienyl)(tBu 2PCMe2CH2)], rapidly formed the arylated heterocycle. Together, these data imply that the rate-determining C-H bond cleavage occurs between PyO and the cyclometalated [Pd(OAc)(tBu 2PCMe2CH2)]2 rather than between PyO and 1. In this case, the resulting heteroarylpalladium complex transfers the heteroaryl group to 1, and C-C bond-formation occurs from (PtBu 3)Pd(Ar)(2-pyridyl oxide). This mechanism proposed for the direct arylation of PyO constitutes an example of C-H bond functionalization in which C-H activation occurs at one metal center and the activated moiety undergoes functionalization after transfer to a second metal center.

Substitution of the nitro group with Grignard reagents: Facile arylation and alkenylation of pyridine N-oxides

The unprecedented substitution of a nitro group with aryl or alkenyl groups of Grignard reagents affords 2-aryl or alkenylpyridine N-oxides in modest to high yields with high chemoselectivity. This protocol allows a simple and clean synthesis of various 2