Metal‐Free Oxidative Cross Coupling of Indoles with Electron‐Rich (Hetero)arenes

Caramenti, Paola; Nandi, Raj Kumar; Waser, Jérôme

doi:10.1002/chem.201802142

Cited by 32 publications

(13 citation statements)

References 73 publications

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“…[25d] Trigonoliimine C (6) has been the subject of three prior total syntheses by the groups of Tambar, Movassaghi, and Ramana, wherein its imine motif was accessed via intramolecular indoxylamine condensation. [25] Our synthesis of 6 began with the advancement of indole 77 (prepared in two steps from commercial materials, see SI) to 2-ethoxyindoxyl intermediate 78, followed by coupling with protected tryptamine 79 [26] (3 equiv). This provided the indole addition product 80, a known precursor to 6, [25b] in 60% yield over the two steps (0.5 mmol scale).…”

Section: Resultsmentioning

confidence: 99%

A General Approach to 2,2-Disubstituted Indoxyls: Total Synthesis of Brevianamide A and Trigonoliimine C

Xu¹,

Smith

2021

Preprint

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The indoxyl unit is a common structural motif in alkaloid natural products and bioactive compounds. Here, we report a general method that transforms readily available 2-substituted indoles into 2,2-disubstituted indoxyls via nucleophile coupling with a 2-alkoxyindoxyl intermediate and showcase its utility in short total syntheses of the alkaloids brevianamide A (7 steps) and trigonoliimine C (6 steps). The developed method is operationally simple and demonstrates broad scope in terms of nucleophile identity and indole substitution, tolerating 2-alkyl substituents and free indole N–H groups, elements beyond the scope of most prior approaches. Spirocyclic indoxyl products are also accessible via intramolecular nucleophilic trapping.

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Section: Resultsmentioning

confidence: 99%

A General Approach to 2,2-Disubstituted Indoxyls: Total Synthesis of Brevianamide A and Trigonoliimine C

Xu¹,

Smith

2021

Preprint

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“…A different method for the arylation of heterocycles under acidic conditions was reported by Waser and co-workers in 2018 (Scheme 5). 13 The methodology is based on conversion of the C-2 and C-3 carbons of indole to the electrophilic center with hypervalent iodine reagents. The method uses unactivated arenes such as thiophene, pyrrole, indole, benzene, and their derivatives as the arylation source.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Recent Advances in the Transition-Metal-Free Arylation of Heteroarenes

Uçar¹,

Daştan²

2021

Synthesis

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Transition-metal-free arylation reactions have attracted considerable attention, because of economic and environmental reasons over the past 40 years. In recent years, in particular, many efforts have been made to develop efficient transition-metal-free approaches for the arylation of heteroarenes. Covering the literature from 2015 to early 2021, this review aims to provide a comprehensive overview of the synthetic and mechanistic aspects of these atom economical and environmentally harmless reactions. 1 Introduction 2 Arylation of Pre-functionalized Heteroarenes 3 Direct C-H Arylation of Heteroarenes 3.1 C(Sp2)-H Arylation 3.2 C(sp3)-H Arylation 4 N-Arylation of Heteroarenes 5 Summary and Outlook

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“…[64][65] C2-substituted indole BX reagents 65a-c were obtained by reaction of trifluoroborate salts with fluorobenziodoxole (Scheme 34b). 66 Scheme 34. Synthesis of Indole-and Pyrrole-BXs.…”

Section: Synthesis Of New Indole-and Pyrrole-bx Reagentsmentioning

confidence: 99%

“…In 2018, we reported a metal-free oxidative cross coupling using TMSCl and HFIP as activators for the synthesis of mixed bi-indoles 74a-c and other mixed heteroaryls 75-77 (Scheme 36). 66 This method allowed the synthesis of bi-heterocycles with complete regioselective installation of functional groups in either one of the two reacting partners. The reasons for the exclusive transfer of the indole heterocycle and the observed high regioselectivity are not well understood at this stage and will require further mechanistic studies.…”

Section: Metal-free Oxidative Cross-coupling For the Synthesis Of MIXmentioning

confidence: 99%

Cyclic Hypervalent Iodine Reagents: Enabling Tools for Bond Disconnection via Reactivity Umpolung

2018

Self Cite

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Conspectus The efficient synthesis of organic compounds is an important field of research, which sets the basis for numerous applications in medicine or materials science. Based on the polarity induced by functional groups, logical bond disconnections can be deduced for the elaboration of organic compounds. Nevertheless, this classical approach makes synthesis rigid, as not all bond disconnections are possible. The concept of Umpolung has been therefore introduced: by inverting the normal polarity of functional groups, new disconnections become possible. Among the tools for achieving Umpolung, hypervalent iodine reagents occupy a privileged position. The electrophilicity of the iodine atom and the reactivity of the hypervalent bond allow access to electrophilic synthons starting from nucleophiles. Nevertheless, some classes of hypervalent iodine reagents can be too unstable for many applications, in particular involving metal catalysis. In this context, cyclic hypervalent iodine reagents, especially benziodoxolones (BXs), have been known for a long time to be more stable than their acyclic counterparts, yet their synthetic potential had not been fully exploited. In this Account, we report our efforts since 2008 on the use of BX reagents in the development of new transformations in organic synthesis, which showed for the first time their versatility as synthetic tools. Our work started with electrophilic alkynylation, as alkynes are one of the most important functional groups in organic chemistry, but are usually introduced as nucleophiles. We used ethynylbenziodoxolones (EBXs) in the direct alkynylation of nucleophiles, such as keto esters, thiols, or phosphines. The reagents could then be applied to the gold- and palladium-catalyzed alkynylation of C–H bonds on (hetero)arenes, leading to a more efficient alternative to the Sonogashira reaction. More complex reactions were then developed with formations of several bonds in a single transformation. Gold- and platinum-catalyzed cyclization/alkynylation domino processes gave access to new types of alkynylated heterocycles. Multifunctionalization of olefins became possible through intramolecular oxy- and amino-alkynylations. (Enantioselective) copper-catalyzed oxy-alkynylation of diazo compounds led to stereocenters with perfect atom economy. Finally, EBXs were also used for the alkynylation of radicals generated under photoredox conditions. Since 2013, we then extended the use of BX reagents to other transformations. Azidobenziodoxol(on)ess (ABXs) were used in the azidation of keto esters, enol silanes, and styrenes. New more stable derivatives were introduced. Cyanobenziodoxolones (CBXs) enabled the cyanation of stabilized enolates, thiols, and radicals. Finally, new BX reagents were developed for the Umpolung of indoles and pyrroles. They could be used in metal-catalyzed directed C–H functionalizations, as well as in Lewis acid mediated oxidative coupling to give functionalized bi(hetero)arenes. In the past decade, our group and others have shown that BX reag...

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Metal‐Free Oxidative Cross Coupling of Indoles with Electron‐Rich (Hetero)arenes

Cited by 32 publications

References 73 publications

A General Approach to 2,2-Disubstituted Indoxyls: Total Synthesis of Brevianamide A and Trigonoliimine C

A General Approach to 2,2-Disubstituted Indoxyls: Total Synthesis of Brevianamide A and Trigonoliimine C

Recent Advances in the Transition-Metal-Free Arylation of Heteroarenes

Cyclic Hypervalent Iodine Reagents: Enabling Tools for Bond Disconnection via Reactivity Umpolung

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Metal‐Free Oxidative Cross Coupling of Indoles with Electron‐Rich (Hetero)arenes

Cited by 32 publications

References 73 publications

A General Approach to 2,2-Disubstituted Indoxyls: Total Synthesis of Brevianamide A and Trigonoliimine C

A General Approach to 2,2-Disubstituted Indoxyls: Total Synthesis of Brevianamide A and Trigonoliimine C

Recent Advances in the Transition-Metal-Free Arylation of Hetero­arenes

Cyclic Hypervalent Iodine Reagents: Enabling Tools for Bond Disconnection via Reactivity Umpolung

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Product

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About

Recent Advances in the Transition-Metal-Free Arylation of Heteroarenes