Pd-catalyzed intramolecular direct arylations at high temperature

Franck, Philippe; Hostyn, Steven; Dajka-Halász, Beáta; Polonka‐Balint, Agnes; Monsieurs, Katrien; Mátyus, Péter; Maes, Bert U. W.

doi:10.1016/j.tet.2008.01.060

Cited by 45 publications

(14 citation statements)

References 32 publications

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“…Other strategies are based on the combination of two palladiumcatalyzed reactions: an amination reaction of halo-genobenzenes with b-aminopyridines followed by ring closure. [7][8][9][10] Herein we report the synthesis of a new class of iodolium heterocycles and their application in a novel strategy to construct the d-carboline core.…”

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confidence: 99%

First Synthesis of Benzopyridoiodolium Salts and Twofold Buchwald-Hartwig Amination for the Total Synthesis of Quindoline

Letessier¹,

Detert²

2011

Synthesis

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The first synthesis of cyclic benzopyridoiodolium salts is described. These hypervalent iodine intermediates are used in an efficient strategy for the construction of the d-carboline core. This novel approach involves a twofold palladium-catalyzed BuchwaldHartwig reaction between these unprecedented reagents and a primary amine. Our methodology successfully provides the expected N-substituted d-carboline core and is efficiently applied in the total synthesis of quindoline.Pyrido [x,y-b]indoles, better known under the common name carbolines, are divided into four different classes according to the position of the nitrogen atom in the pyridine ring. Whereas a large group of alkaloids is based on the bcarboline core, 1,2 d-carbolines belong to a much less represented group of pyridoindoles, in nature as well as in synthetic chemistry.A small number of d-carbolines have been isolated from natural sources, they are all benzo-fused and also known as quindolines 3 1-5 ( Figure 1). All these indolo[3,2-b]quinolines were extracted from Cryptolepis Sanguinolenta and Justica betonica, two indigenous plants from west Africa and India. Extracts of these plants are used in the dyeing of leather and textiles, as well as in traditional medicine in West and Central Africa, including the treatment of malaria, and infections of the respiratory and urinary tracts. 3,4 Recently, we reported that b-and g-carbolines can be efficiently synthesized via rhodium-or ruthenium-catalyzed [2+2+2] cycloadditions of nitriles to alkynyl-ynamides. 5 However, this synthetic strategy does not allow the synthesis of the isomeric a-and d-carbolines.Only a few synthetic strategies for the construction of the d-carboline core are described the literature. One of the first applied synthetic routes is based on the GraebeUllmann reaction. 6 Similarly to the synthesis of carbazoles, 1-pyridin-3-yl-1H-1,2,3-benzotriazoles are used as intermediates to obtain d-carboline derivatives. Other strategies are based on the combination of two palladiumcatalyzed reactions: an amination reaction of halogenobenzenes with b-aminopyridines followed by ring closure. 7-10 Herein we report the synthesis of a new class of iodolium heterocycles and their application in a novel strategy to construct the d-carboline core.As part of our interest in carbazoles and related heterocycles, 1,11 we applied Olofsson and Merritt's synthesis of diaryliodonium triflates 12 to the preparation of dibenzoiodolium salts. 13 The oxidation of an o-iodobiphenyl with m-chloroperoxybenzoic acid to an iodoso derivative followed by protonation with triflic acid results in remote functionalization of the o¢-position, giving the desired dibenzoiodolium salt with non-nucleophilic triflate as an anion. N-Substituted carbazoles are obtained in twofold palladium-catalyzed aminations with primary amines. 13Applying this methodology to 3-iodo-2-phenylpyridine (9), we were able to obtain benzopyridoiodolium triflate 10. To the best of our knowledge, these are the first examples of aza-analogous benzoiodoli...

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First Synthesis of Benzopyridoiodolium Salts and Twofold Buchwald-Hartwig Amination for the Total Synthesis of Quindoline

Letessier¹,

Detert²

2011

Synthesis

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“…13 After observing the generation of 13a by TLC analysis, we added a PdCl 2 (PPh 3 ) 2 catalyst, NaOAc, and DMA in accordance with the Maes' procedure. 14 The resultant mixture was heated under microwave irradiation (160 °C, 1 h). The desired product 1a was obtained in 32% yield (one-pot, two-step yield).…”

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confidence: 99%

Synthesis of Pyrazolofuropyrazine via One-Pot SNAr Reaction and Intramolecular Direct C–H Arylation

et al. 2018

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Fused-ring systems containing heterocycles are attractive templates for drug discovery. Biologically active 6-5-5+6 fused-ring systems that possess heterocycles are available, but these require a relatively large number of synthetic steps for preparation. Therefore, pyrazolofuropyrazine was designed as a 6-5-5+6 ring system template that incorporates ready accessibility for drug discovery. Pyrazolofuropyrazines were successfully constructed in only a few steps via one-pot SNAr reaction/intramolecular C–H direct arylation. As a drug candidate, pyrazolofuropyrazine has earned a favorable LogP, although significant biological activity has yet to be established; the ready accessibility of pyrazolofuropyrazine template, however, offers an opportunity for the rapid development of promising new drug candidates.

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“…For -Carboline, see: Subbaraju et al (2004); Paulo et al (2000); Chernyshev et al (2001); Namjoshi et al (2011); Qu et al (2009); Masterova et al (2008). For synthetic strategies to carbolines, see: Spä th & Eiter (1940); Sakamoto et al (1999); Franck et al (2008). For the transition-metal-catalyzed synthesis of carbazoles, see: Letessier (2011); Nemkovich et al (2009).…”

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5-Benzyl-5H-pyrido[3,2-b]indole

2011

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The title compound, C18H14N2, was prepared by twofold Pd-catalyzed arylamination of a cyclic pyrido–benzo–iodolium salt. In the crystal, two molecules of 9-benzyl-δ-carboline form centrosymmetrical dimers with distances of 3.651 (2) Å between the centroids of the pyridine rings and 3.961 (2) Å between the centroids of the pyrrole and pyridine rings. The phenyl rings point to the other molecule in the dimer and the carboline core is essentially planar [maximum deviation of 0.027 (2) Å].

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Pd-catalyzed intramolecular direct arylations at high temperature

Cited by 45 publications

References 32 publications

First Synthesis of Benzopyridoiodolium Salts and Twofold Buchwald-Hartwig Amination for the Total Synthesis of Quindoline

First Synthesis of Benzopyridoiodolium Salts and Twofold Buchwald-Hartwig Amination for the Total Synthesis of Quindoline

Synthesis of Pyrazolofuropyrazine via One-Pot SNAr Reaction and Intramolecular Direct C–H Arylation

5-Benzyl-5H-pyrido[3,2-b]indole

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