The industrially important coupling of aromatic compounds has generally required differential prefunctionalization the arene partners with a halide and an electropositive group. Here we report that palladium, in conjunction copper oxidant, can catalyze cross-coupling N -acetylindoles benzenes high yield regioselectivity across range indoles without recourse to activating groups. These reactions are completely selective for cross-coupling, no products arising from indole or benzene...

The oxidative synthesis of highly functionalized indoles from simple anilines and internal alkynes mediated by a rhodium(III) catalyst is described. Good yields are obtained for variety aniline substrates, good regioselectivity the more sterically accessible position when meta-substituted used. Symmetrical unsymmetrical react efficiently with high (>40:1) C2/C3 aryl/alkyl substituted

Recently, the rhodium(III)-complex [Cp*RhCl2]2 1 has provided exciting opportunities for efficient synthesis of aromatic heterocycles based on a rhodium-catalyzed C−H bond functionalization event. In present report, use complexes and its dicationic analogue [Cp*Rh(MeCN)3][SbF6]2 2 have been employed in formation indoles via oxidative annulation acetanilides with internal alkynes. The optimized reaction conditions allow molecular oxygen to be used as terminal oxidant this process, may carried...

By changing the stoichiometric oxidant and modifying indole N-substituent in palladium-catalyzed oxidative arene cross-coupling reactions, both C2 C3 arylation can be achieved high yield. High regioselectivity also with benzene component, use of this methodology pyrrole substrates is illustrated. A mechanistic hypothesis for change C2/C3 selectivity advanced.

Palladium-catalyzed direct arylation reactions are described with a broad range of azine and azole N-oxides. In addition to aspects functional group compatibility, issues regioselectivity have been explored when nonsymmetrical N-oxides used. these cases, both the choice ligand nature substituents play important roles in determining regioisomeric distribution. When employed, preferential reaction is observed for at C2 which occurs under very mild conditions. Subsequent occur C5 followed by...

New reaction conditions for intramolecular palladium(II)-catalyzed oxidative carbon−carbon bond formation under air are described. The use of pivalic acid as the solvent, instead acetic acid, results in greater reproducibility, higher yields, and broader scope. This includes electron-rich diarylamines illustrated synthesis three naturally occurring carbazole products: Murrayafoline A, Mukonine, Clausenine. A variety side products have also been isolated, casting light on competing pathways...

Rho-Rho-Rho your boat: A rhodium catalyst effects the regioselective oxidative coupling of enynes with N-aryl ureas (X=NR2) and N-vinylacetamides (X=C(O)Me), affording corresponding 2-alkenylindoles 2-alkenylpyrroles in good yield. Simple hydrogenation delivers C2/C3-aliphatic-substituted indole or pyrrole (see scheme). Detailed facts importance to specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited typeset. They made available...

Detailed mechanistic studies on the palladium-catalyzed direct arylation of pyridine N-oxides are presented. The order each reaction component is determined to provide a general picture. C-H bond cleaving step examined in further detail through computational studies, and calculated results support an inner-sphere concerted metalation-deprotonation (CMD) pathway. Competition experiments were conducted with varying electronic characters, revealed enhancement rate when using more...

Abstract Described here is an efficient method to access highly functionalized arynes from unsymmetrical aryl(mesityl)iodonium tosylate salts. The iodonium salts are prepared in a single pot either commercially available aryl iodides or arylboronic acids. aryne intermediates generated by ortho ‐C−H deprotonation of salt with amide base and trapped cycloaddition reaction furan moderate good yields. Coupling partners for the beyond also described, including benzyl azide alicyclic amine...

Mit einem Rhodiumkatalysator gelingt die regioselektive oxidative Kupplung von Eninen mit N-Arylharnstoffen (X=NR2) und N-Vinylacetamiden (X=C(O)Me) unter Bildung der jeweiligen 2-Alkenylindole 2-Alkenylpyrrole in guten Ausbeuten. Eine einfache Hydrierung ergibt aliphatisch an C2/C3-Position substituierten Indole bzw. Pyrrole (siehe Schema). Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or...

Diaryliodonium salts have recently attracted significant attention as metal-free-arylation reagents in organic synthesis, and efficient access to these is critical for advancement of their use reaction discovery development. The trimethoxybenzene-derived auxiliary a promising component unsymmetrical variants, yet remains limited. Here, one-pot synthesis aryl(2,4,6-trimethoxyphenyl)iodonium from aryl iodides, m-CPBA, p-toluenesulfonic acid, trimethoxybenzene described. Optimization the...

A regio- and chemoselective C–H deprotonative strategy toward arynes is described that employs a hypervalent iodine leaving group. The unsymmetrical aryl(mesityl)iodonium salts used as aryne precursors are readily synthesized from commercially available aryl iodide arylboronic acid building blocks. bases LiHMDS NaO<i>t</i>-Bu engage the diaryliodonium in deprotonation event at an aromatic bond transient react cycloaddition reactions with furan benzyl azide or nucleophilic addition reaction...

Abstract A mild and metal‐free approach to C−N coupling is described that employs diaryliodonium salt electrophiles secondary aliphatic amine nucleophiles. This reaction results in direct ipso‐substitution of the iodonium moiety unsymmetrical aryl(TMP)iodonium salts are primarily employed. Moreover, arene substituents substitution patterns currently pose a challenge classical methods accommodated alicyclic nucleophiles used here unprecedented other contemporary reactions.

Abstract Herein, the synthesis of 1,2,3,4‐tetrasubstituted benzenoid rings, motifs found in pharmaceutical, agrochemical, and natural products, is described. [1] In past, regioselective syntheses such compounds have been a significant challenge. This work reports method using substituted arynes derived from aryl(Mes)iodonium salts to access range densely functionalized rings. Significantly, it was that halide substituents are compatible under these conditions, enabling post‐synthetic...

Previous analyses have revealed that benzenoid rings are prevalent scaffolds in active pharmaceutical ingredients (APIs). Here, we analyze the substitution patterns of small molecule APIs approved by FDA through 2019 and show only a few (1-, 1,2-, 1,4-, 1,2,4-) prevail, distribution has remained relatively constant over time. We postulate connection between available synthetic methods occurrence providing an overview elaborate existing those create new patterns, including former favored...

Arynes offer immense potential for diversification of benzenoid rings, which occur in pharmaceuticals, agrochemicals, and liquid crystals. However, accessing these high-energy intermediates requires synthetic precursors, involve either harsh conditions or multistep syntheses. The development alternative methods to access arynes using simpler substrates milder is necessary a more streamlined approach. Here, we describe two-step formal dehydrogenation simple arenes generate at remote position...

The base mediated coupling of aliphatic alcohol pronucleophiles with unsymmetric diaryliodonium salt electrophiles is described. This metal-free reaction operationally simple, proceeds at mild temperature, and displays broad substrate scope to generate industrially important alkyl-aryl ethers in moderate excellent yield. synthetic utility these reactions demonstrated, aspects sustainability are highlighted by the use aryl(mesityl)iodonium arylating reagents.

The direct synthesis of aryl(2,4,6-trimethoxyphenyl)iodonium trifluoroacetate salts from aryl iodides is described. Stoichiometric quantities trifluoroacetic acid and trimethoxybenzene are used as the counteranion auxiliary precursors, respectively, under oxidizing conditions. reaction occurs at mild temperature, broad in scope, does not require a separate anion exchange step to install group. intermediacy two distinct dicarboxy aryl-λ3-iodanes hypothesized mechanism.

Arenes are broadly found motifs in societally important molecules. Access to diverse arene chemical space is critically important, and the ability do so from common reagents highly desirable. Aryl(TMP)iodonium tosylates provide one such access point via aryl intermediates. Here we demonstrate that controlling reaction pathways selectively leads arynes with a broad scope of arenes arynophiles (24 examples, 70% average yield) efficient biologically active compounds.

A revised bonding model for diarylhalonium salts, that involves partial s-orbital contribution, provides new insight into periodic trends in structure and reactivity.

Modular C–N coupling is a desirable way to construct N-aryl carbamates, which are privileged scaffolds in active pharmaceutical ingredients. However, there no broadly applicable metal-free methods for theN-arylation of carbamates. Herein, we describe approach that uses aryl(TMP)iodonium salts as arylation reagents cyclic carbamates by exploiting the metal-like reactivity iodine(III). The scope includes 25 examples, including 17 different and 9 yields ranging between 55 97% (75% avg).

Arynes are versatile intermediates for organic synthesis and now they can be accessed from arenes in one or two-pot sequences via aryl thianthrenium ( situ ) iodonium (isolated) intermediates, respectively.

Diaryliodonium salts continue to emerge as versatile arylation reagents. This is especially true for unsymmetrical aryl(TMP)iodonium (TMP = 2,4,6-trimethoxyphenyl) because they undergo highly selective aryl transfer across diverse mechanistic settings. account outlines our motivation exploring the chemistry of and efforts develop streamlined synthetic methods access them novel reactions that use them.