Synthesis of Fluoroazaindolines by an Uncommon Radical <i>ipso</i> Substitution of a Carbon−Fluorine Bond

Laot, Yann; Petit, Laurent; Zard, Samir Z.

doi:10.1021/ol101240f

Cited by 28 publications

(17 citation statements)

References 36 publications

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“…Some examples 57a-h are given in Scheme 10 starting with azaindoline 56a. 24 It is also possible to convert the substituted azaindoline product into the an azaindole, such as 58, but a strong oxidising agent is required (IBX in DMSO) 25 and the yield is modest, albeit unoptimised, no doubt reflecting the strong deactivating effect of the difluoropyridine motif.…”

Section: Methodsmentioning

confidence: 99%

“…[24][25][26]. This rather unique transformation is pictured at the top of Scheme 9 along with a few examples.…”

Section: Pmb = P-methoxybenzylmentioning

confidence: 95%

“…24 The carbon-fluorine bond is one of the strongest in organic chemistry, yet it seems possible to cleave it homolytically …”

Section: Scheme 8 Synthesis Of Fluorinated Arylpiperidinesmentioning

confidence: 99%

“…Thus, in the same manner as for the transformations in Scheme 9, it proved possible to add xanthate 83 to olefin 53 and to force the cyclisation of adduct 108 into trifluoroazaindoline 109 with concomitant expulsion of a fluorine atom by heating with di-t-butyl peroxide in refluxing o-dichlorobenzene. 24 Scheme 26 Synthesis of pyridine and pyrimidine derivatives.…”

Section: Scheme 25 Synthesis Of 11-difluoroalkenesmentioning

confidence: 99%

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The xanthate route to organofluorine derivatives. A brief account

Zard

2016

Org. Biomol. Chem.

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The present account summarises routes to organofluorine derivatives based on the chemistry of xanthates developed in the author's laboratory. It concerns mostly radical pathways, but a few ionic transformations are also discussed. The degenerative reversible transfer of xanthates allows radical addition even to unactivated alkenes and tolerates numerous functional groups, in particular common polar groups such as ketones, esters, amides, carbamates, nitriles etc. Since the fluorine atoms can be placed on the alkene or the xanthate partner or on both, this opens a convergent approach to a vast array of otherwise inaccessible organofluorine structures that could be of interest to the pharmaceutical and agrochemical industries and to materials science.

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Section: Methodsmentioning

confidence: 99%

“…[24][25][26]. This rather unique transformation is pictured at the top of Scheme 9 along with a few examples.…”

Section: Pmb = P-methoxybenzylmentioning

confidence: 95%

“…24 The carbon-fluorine bond is one of the strongest in organic chemistry, yet it seems possible to cleave it homolytically …”

Section: Scheme 8 Synthesis Of Fluorinated Arylpiperidinesmentioning

confidence: 99%

Section: Scheme 25 Synthesis Of 11-difluoroalkenesmentioning

confidence: 99%

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The xanthate route to organofluorine derivatives. A brief account

Zard

2016

Org. Biomol. Chem.

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“…[41] It reacts with allylamine chiefly at the 4-position to give after acetylationa cetamide 72,ac ompound that reacts readily with xanthates 1 to give the usual adducts 73 (Scheme12). [42] Under somewhat forcing conditions, namely heatingw ith di-tert-butyl peroxidei nr efluxing chlorobenzene or amyl acetate, ar are homolytic ipso substitution of af luorine takes place to give azaindoline 76.T he sequence proceeding via intermediates 74 and 75 and final extrusion of af luorine atom appears to be the mostl ikely pathway,a sa ll other alternatives are less reasonable. [42][43][44] Homolytic rupture of a carbon-fluorineb ond is very rare, but the substantial increase in entropyi nt he last fragmentation step and, especially, the restoration of aromaticity are strong driving forces.…”

Section: The Case Of Fluoropyridinesmentioning

confidence: 99%

The Xanthate Route to Indolines, Indoles, and their Aza Congeners

Zard

2020

Chemistry A European J

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Convergentr outes to av ariety of indolines, indoles, oxindoles, and their aza analogues involving radical additions of xanthates are described. Three approaches are summarized. The first is the least general and relies on the generation of aryl or heteroaryl radicals startingf rom diazonium salts. The second involves radical addition to N-allylanilines followed by ring-closure onto the aromatic core. A large varietyo fi ndolines and azaindolines can thus be obtained and, in many cases, converted into the corresponding indoles and azaindoles by variousm ethods. Thes ynthesiso f novel fluoroazaindolines and fluoroazaindoles by ar are homolytic ipso-substitution of fluorine atoms is particularly noteworthy.T he last approachh inges on the direct modification of indoles by radical addition to the pyrrole subunit of the indolen ucleus. Application of this methodology to the total synthesis of melatonin andt he alkaloids mersicarpine, caulerpine, and the pentacyclic skeleton of tronocarpine is briefly discussed. Mosto ft he compounds described herein would be difficult to obtain by more traditional routes.

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Radical Arylations

Vaillard

Studer

2012

Encyclopedia of Radicals in Chemistry, Biology and Materials

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This article reports on radical arylations, also highlighting the very important early achievements in this field. Included are the Meerwein arylation and the Pschorr reaction. Intramolecular homolytic aromatic substitutions with aryl radicals and various arene radical acceptors for the formation of biaryls are discussed. Along with reactive aryl radicals, nucleophilic and also electrophilic alkyl radicals can cyclize with arenes providing products of intramolecular homolytic aromatic substitution. Discussion on the mechanism is provided. Moreover, it is shown that this chemistry has been successfully used in complex natural‐products synthesis. A section is devoted to radical aryl migration reactions. Finally, reactions of aryl radicals with olefins are discussed. It is also shown that aryl radicals react efficiently with various heteroatom‐based radical acceptors for aryl‐X bond formation (X = Se, S, Te, B, P).

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Synthesis of Fluoroazaindolines by an Uncommon Radical ipso Substitution of a Carbon−Fluorine Bond

Abstract: Rare examples of a synthetically useful radical ipso substitution of a carbon-fluorine bond are reported. Highly functionalized fluoroazaindoline structures have thus been prepared with use of cheap and readily available substrates and reagents.

Cited by 28 publications

References 36 publications

The xanthate route to organofluorine derivatives. A brief account

The xanthate route to organofluorine derivatives. A brief account

The Xanthate Route to Indolines, Indoles, and their Aza Congeners

Radical Arylations

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