Selective synthesis of 2-substituted pyridine N-oxides via directed ortho-metallation using Grignard reagents

Andersson, Hans; Gustafsson, Magnus; Olsson, Roger; Almqvist, Fredrik

doi:10.1016/j.tetlet.2008.09.104

Cited by 32 publications

(14 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly, it was found that directed orthometallation of pyridine-N-oxides with a Grignard reagent followed by treatment with diphenyliodonium triflate in the presence of [Pd(PPh 3 ) 4 ] and ZnCl 2 delivered the 2-phenylated product. [111] Yamazaki and co-workers reported a reductive coupling of diaryliodonium salts by treatment with a stoichiometric quantity of zinc powder in the presence of a palladium catalyst, furnishing biaryls in excellent yields. [112] Conducting the same reductive coupling under an atmosphere of carbon monoxide afforded arylketones in moderate yield.…”

Section: Angewandte Chemiementioning

confidence: 99%

Diaryliodonium Salts: A Journey from Obscurity to Fame

2009

View full text Add to dashboard Cite

The recent groundbreaking developments in the application of diaryliodonium salts in cross-coupling reactions has brought this class of previously underdeveloped reagents to the forefront of organic chemistry. With the advent of novel, facile, and efficient synthetic routes to these compounds, many more applications can be foreseen. Herein we provide an overview of the historical and recent advances in the synthesis and applications of diaryliodonium salts.

show abstract

Section: Angewandte Chemiementioning

confidence: 99%

Diaryliodonium Salts: A Journey from Obscurity to Fame

2009

View full text Add to dashboard Cite

show abstract

“…With such a complex, we could evaluate whether the reaction of such a complex with the arylpalladium carboxylate complex 1 was sufficiently fast to be part of the catalytic cycle. Because of the known difficulty in generating 2-metallated pyridine oxides, 13 which would be used to generate 2-pyridyloxide palladium complexes, in high yield, we conducted studies on 2-benzothienylpalladium complexes. Benzothiophene undergoes catalytic direct arylation under conditions similar to those of PyO.…”

mentioning

confidence: 99%

Mechanistic Studies on Direct Arylation of Pyridine N-Oxide: Evidence for Cooperative Catalysis between Two Distinct Palladium Centers

2012

View full text Add to dashboard Cite

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) and the reaction of this complex with PyO. We provide strong evidence that (PtBu3)Pd(Ar)(OAc) does not react directly with pyridine N-oxide. Instead, our data imply that the cyclometallated complex [Pd(OAc)(tBu2PCMe2CH2)]2, which is generated from the decomposition of (PtBu3)Pd(Ar)(OAc), reacts with PyO and serves as a catalyst for the reaction of PyO with (PtBu3)Pd(Ar)(OAc). The reaction of PyO with (PtBu3)Pd(Ar)(OAc) occurs with an induction period, and the reaction of (PtBu3)Pd(Ar)(OAc) with excess PyO in the presence of [Pd(OAc)(tBu2PCMe2CH2)]2 is zero-order in (PtBu3)Pd(Ar)(OAc). 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 (PtBu3)Pd(Ar)(OAc) with the model heteroarylpalladium complex containing a cyclometallated phosphine [(PEt3)Pd(2-benzothienyl)(tBu2PCMe2CH2)] rapidly formed the arylated heterocycle. Together, these data imply that the rate-determining C-H bond cleavage occurs between PyO and the cyclometallated [Pd(OAc)(tBu2PCMe2CH2)]2, rather than between PyO and (PtBu3)Pd(Ar)(OAc). In this case, the resulting heteroarylpalladium complex transfers the heteroaryl group to (PtBu3)Pd(Ar)(OAc), and C-C bondformation occurs from (PtBu3)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.

show abstract

“…Table 14.9 and Table 14.10 present a potpourri of DoM-Kumada-Corriu-derived biaryl and heterobiaryl syntheses demonstrating the scope of DMGs and prevalence of Ni(0) catalysis. In the Ar-Ar-bond-forming series (Table 14.9) [66][67][68][69][70], the lack of functional-group complexity in either ArMgX and ArLG coupling partners and the impact of steric effects (entry 7) are noted; equally uninformative is the current short list of HetArMgX-HetArLG cross-coupling reactions (Table 14.10) [59b, [71][72][73]. The pyridine N-oxide Grignard reagent (entry 4), generated by the addition of n-BuMgCl at −78 • C to the corresponding pyridine N-oxide, may be an indication of new cross-coupling reactivity.…”

Section: → Magnesium Transmetallation the Kumada-corriu Cross-coumentioning

confidence: 99%

“…This conceptual 1,2-dipole synthetic equivalent (Scheme 14.10) has been reasonably well tested using simple, not necessarily always aromatic, Grignard reagents and these have been compared with the [73] corresponding OTf-Grignard cross-coupling processes (Table 14.11) [68,[75][76][77]. Latitude has also been taken to include examples that, although not derived from DoM processes, embody such potential (entries 6, 7).…”

Section: → Magnesium Transmetallation the Kumada-corriu Cross-coumentioning

confidence: 99%