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Chiral organoboronates have played a critical role in organic chemistry and in the development of materials science and pharmaceuticals. Much effort has been devoted to exploring synthetic methodologies for the preparation of these compounds during the past few decades. Among the known methods, asymmetric catalysis has emerged as a practical and highly efficient strategy for their straightforward preparation, and recent years have witnessed remarkable advances in this respect. Approaches such as asymmetric borylative addition, asymmetric allylic borylation and stereospecific cross-coupling borylation, have been extensively explored and well established employing transition-metal catalysis with a chiral ligand. This review provides a comprehensive overview of transition metal-catalysed asymmetric borylation processes to construct carbon–boron, carbon–carbon, and other carbon–heteroatom bonds. It summarises a range of recent achievements in this area of research, with considerable attention devoted to the reaction modes and the mechanisms involved.

A novel transformation for the construction of Csp3-Csp bonds was achieved via a photo-induced copper-catalysed C-C bond cleavage. This approach was applied to prepare a series of highly functionalized alkynyl nitriles using readily available cyclobutanones and terminal alkynes. Mechanistic exploration showed that the in situ generated copper acetylide complex is an effective photosensitive catalyst to promote the C-C bond cleavage of cycloketoxime esters through a radical process.

An efficient method for the construction of gem-difluoroallylsilanes with high enantiomeric excess via a copper-catalysed defluorosilylation of trifluoromethylated alkenes with silylboronates is described. The key to this high enantioselectivity is the careful selection of NaOH as the base and using a triazolium-based chiral N-heterocyclic carbene (NHC) as a ligand in the presence of a copper catalyst. The reaction conditions are mild, and excellent functional group compatibility is observed. This strategy addresses the limitations of the previously described base-mediated defluorosilylation under transition metal-free conditions, which can lead to erosion of the enantioselectivity. The synthetic utilities of the obtained gem-difluoroallylsilanes are also presented. Computational and experimental data suggest that the reaction proceeds through the enantioselective insertion of silyl-Cu/NHC species into the double bond of trifluormethyl alkenes and the Cu-mediated β-F elimination steps.

Organoboron reagents are important synthetic intermediates that have a key role in the construction of natural products, pharmaceuticals and organic materials1. The discovery of simpler, milder and more efficient approaches to organoborons can open additional routes to diverse substances2-5. Here we show a general method for the directed C-H borylation of arenes and heteroarenes without the use of metal catalysts. C7- and C4-borylated indoles are produced by a mild approach that is compatible with a broad range of functional groups. The mechanism, which is established by density functional theory calculations, involves BBr3 acting as both a reagent and a catalyst. The potential utility of this strategy is highlighted by the downstream transformation of the formed boron species into natural products and drug scaffolds.

A practical single-electron-transfer-induced selective C(sp3)–N coupling of cycloketoximes with anilines via C–C bond cleavage under copper-catalytic and synergetic photoredox/copper-catalytic reac...

Rhodium-catalyzed C7-selective decarbonylative trideuteromethylation of indoles with commercially available Ac2O-d6 via C-H and C-C bond activation has been developed. The key to the high reactivity and regioselectivity of this transformation is the appropriate choice of an indole N-PtBu2 chelation-assisting group. This method has many advantages, including easy access and removal of the directing group, the use of cheap and widely available deuterium methylating source, no requirement of an external ligand or oxidant, a broader substrate scope, high efficiency, and the sole regioisomer.

Alkyl groups are one of the most widely used groups in organic synthesis. Here, a a series of thianthrenium salts have been synthesized that act as reliable alkylation reagents and readily engage in copper-catalyzed Sonogashira reactions to build C(sp3 )-C(sp) bonds under mild photochemical conditions. Diverse alkyl thianthrenium salts, including methyl and disubstituted thianthrenium salts, are employed with great functional breadth, since sensitive Cl, Br, and I atoms, which are poorly tolerated in conventional approaches, are compatible. The generality of the developed alkyl reagents has also been demonstrated in copper-catalyzed Kumada reactions.

Transition metal (TM)-catalysed directed hydroboration of aliphatic internal olefins which facilitates the construction of complex alkylboronates is an essential synthetic methodology. Here, an efficient method for the borylation of cyclopropanes involving TM-catalysed directed C–C activation has been developed. Upon exposure to neutral Rh(i)-catalyst systems, N-Piv-substituted cyclopropylamines (CPAs) undergo proximal-selective hydroboration with HBpin to provide valuable γ-amino boronates in one step which are otherwise difficult to synthesize by known methods. The enantioenriched substrates can deliver chiral products without erosion of the enantioselectivities. Versatile synthetic utility of the obtained γ-amino boronates is also demonstrated. Experimental and computational mechanistic studies showed the preferred pathway and the origin of this selectivity. This study will enable the further use of CPAs as valuable building blocks for the tunable generation of C–heteroatom or C–C bonds through selective C–C bond activation., Transition metal (TM)-catalysed directed hydroboration of cyclopropanes which facilitates the construction of complex alkylboronates is an essential synthetic methodology.

The widespread presence of hydrocarbons makes C-H functionalization an attractive alternative to traditional cross-coupling methods. As indole is an important heteroarene in a plethora of natural products and pharmaceuticals, C-H functionalization of indole moieties has emerged as one of the most important topics in this field. Due to the presence of multiple C-H bonds in indoles, site selectivity is a long-standing challenge. Much effort has been devoted to the C-H functionalization of indoles at the C3 or C2 position, while accessing the benzene core (from C4 to C7) is considerably more challenging.This Account summarizes our recent efforts toward site-selective C-H functionalization of indoles at the benzene core based on innovative strategies. A common method to solve the issue involves the development of directing groups (DGs). Our early studies establish that the installation of the N-P(O)tBu2 group at the N position can produce C7 and C6 arylation products using palladium and copper catalysts, respectively. The developed system can also be extended to direct arylation of indoles at the C5 and C4 positions by installing a pivaloyl group at the C3 position. Further investigation of indoles bearing N-PtBu2 groups shows a more diverse reactivity for C-H functionalizations at the C7 position, including arylation, olefination, acylation, alkylation, silylation, and carbonylation with different coupling partners. Compared to the P(V) DG, the P(III) group can be easily attached to the indole substrates and detached from the products. However, these attractive reactions rely mostly on precious metal catalysts with ligands; this requirement can be a significant limitation, particularly for large-scale syntheses and the necessity of removal of toxic trace metals in pharmaceutical products. We have also uncovered a general strategy for chelation-assisted aromatic C-H borylation just using simple BBr3 under mild conditions, in which the installation of pivaloyl groups at the N1 or C3 position of indoles can selectively deliver the boron species to the unfavorable C7 or C4 positions and allow subsequent C-H borylation without any metal. This transition-metal-free strategy can be extended to synthesize C7 and C4 hydroxylated indoles by boron-mediated directed C-H hydroxylation under mild reaction conditions and with broad functional group compatibility.In this Account, we describe our contributions to this topic since 2015. These studies provide efficient and attractive methods for the divergent synthesis of valuable substituted indoles and insights into the exploration of new strategies for the site-selective C-H functionalization and directives for other important heteroarenes.

Sulfonium salts bearing a positively charged sulfur atom with three organic substituents have intrigued chemists for more than a century for their unusual structures and high chemical reactivity. These compounds are known to undergo facile single-electron reduction to emerge as a valuable and alternative source of aryl radicals for organic synthesis. However, the generation of non-stabilized alkyl radicals from sulfonium salts has been a challenge for several decades. Here we report the treatment of S-(alkyl) thianthrenium salts to generate non-stabilized alkyl radicals as key intermediates granting the controlled and selective outcome of the ensuing reactions under mild photoredox conditions. The value of these reagents has been demonstrated through the efficient construction of alkylboronates and other transformations, including heteroarylation, alkylation, alkenylation, and alkynylation. The developed method is practical, and provides the opportunity to convert C–OH bond to C–B and C–C bonds., The generation of non-stabilized alkyl radicals from sulfonium salts has been a challenge for several decades. Here, the authors show the treatment of S-(alkyl) thianthrenium salts, which can generate non-stabilized alkyl radicals as key intermediates that enable controlled and selective reactions under mild photoredox conditions.

Heteroarenes containing carbon–silicon (C–Si) bonds are important building blocks that play an important role in the construction of natural products, pharmaceuticals, and organic materials. In this context, the C–H silylation of heteroarenes is a topic of intense interest. Indole C–H silylation can preferentially occur at the nucleophilic C3 and C2 position (pyrrole core), while accessing the C4-C7 positions (benzene core) of the indole remains highly challenging. Here, we show a general strategy for the regioselective C7-H silylation of indole derivatives. Mainly, the regioselectivity is determined by strong coordination of the palladium catalyst with phosphorus (III) directing group. Using this expedient synthetic strategy, the diverse C7-silylated indoles are synthesized effectively which exhibits the broad functional group compatibility. Moreover, this protocol also been extended to other heteroarenes such as carbazoles. The obtained silylated indoles have been employed in various transformations to enable the corresponding differently functionalized indole derivatives. Significantly, a cyclopalladated intermediate is successfully synthesized to test the hypothesis about the P(III)-directed C–H metalation event. A series of mechanistic experiments and density functional theory (M06-2X) calculations has shown the preferred pathway of this directed C–H silylation process., Indole C-H silylation preferentially occurs at the C3 and C2 positions, while functionalization of the benzene core (C4-C7 sites) remains challenging. Here, the authors report a regioselective C7-H silylation of indole derivatives assisted by strong coordination of the palladium catalyst with a phosphorus directing group.

Organoborons have emerged as versatile building blocks in organic synthesis to achieve molecular diversity and as carboxylic acid bioisosteres with broad applicability in drug discovery. Traditionally, these compounds are prepared by the substitution of Grignard/lithium reagents with electrophilic boron species and Brown hydroboration. Recent developments have provided new routes for the efficient preparation of organoborons by applying reactions using chemical feedstocks with leaving groups. As compared to the previous methods that used organic halides (I, Br, and Cl), the direct borylation of less reactive C-Het and C-C bonds has become highly important to get efficiency and functional-group compatibility. This Review aims to provide a comprehensive overview of this topic, including (1) C-F bond borylation, (2) C-O bond borylation, (3) C-S bond borylation, (4) C-N bond borylation, and (5) C-C bond borylation. Considerable attention is given to the strategies and mechanisms involved. We expect that this Review will inspire chemists to discover more efficient transformations to expand this field.

Pd-catalyzed C7-selective C–H carbonylation of indoles with CO using BQ, a key external oxidant, is demonstrated., The first development of an external oxidant-compatible system involving a phosphorus(III)-directed C–H functionalization has been uncovered. An efficient C–H esterification of indoles with CO and alcohols has been reported in which the high reactivity and the exclusive C7-selectivity derives from the selection of a P(III)–directing group and the utilization of benzoquinone as an external oxidant with palladium catalysis. This strategy shows many advantages, involving an easily accessible and removable directing group, the use of cheap carbonylation sources, a broad substrate scope, and excellent positional selectivity. Two cyclopalladated intermediates were confirmed by x-ray analysis, uncovering key mechanistic features of this P(III)-directed C–H metalation event.

Transition-metal-mediated metalation of an aromatic C-H bond that is adjacent to a tertiary phosphine group in arylphosphines via a four-membered chelate ring was first discovered in 1968. Herein, we overcome a long-standing problem with the ortho-C-H activation of arylphosphines in a catalytic fashion. In particular, we developed a rhodium-catalyzed ortho-selective C-H borylation of various commercially available arylphosphines with B2 pin2 through PIII -chelation-assisted C-H activation. This discovery is suggestive of a generic platform that could enable the late-stage modification of readily accessible arylphosphines.

The first example of intramolecular ring-opening and reconstruction of cyclobutanone oxime esters via selective C-C bond cleavage leading to the synthesis of 3,4-dihydronaphthalene-2-carbonitriles in the presence of a cheap copper catalyst has been reported. The protocol is distinguished by mild and safe reaction conditions that exclude ligands, oxidants, bases, toxic cyanide salts and tolerates a wide scope of cyclobutanones without compromising their efficiency and scalability. The alternative visible-light-driven photoredox process for this coupling reaction was also uncovered.

Methods to incorporate deuterium atoms into organic molecules are valuable for the pharmaceutical industry. Here, we found that diboron reagents can efficiently mediate the transfer of two D atoms from heavy water directly onto alkynes through copper-catalysed cis-selective semihydrogenation. Avoiding the use of costly and flammable D2 gas, this safe and practical process can proceed with excellent chemoselectivity and stereoselectivity. Utilizing the present method as the key step, the formal asymmetric total synthesis of d2-deuterium-labeled cis-combretastatin A4 is demonstrated. Mechanistic studies suggest that monoborylation of alkynes is the key step for this semihydrogenation process.

A novel transformation for the construction of Csp

The first aromatic C-H silylation between arylphosphines and hydrosilanes enabled by a ruthenium complex has been developed. The excellent ortho-selectivity results from a four-membered metallacyclic intermediate involving phosphorus chelation. The developed system can be extended to the benzylic C-H silylation of arylphosphines. Diverse silylated arylphosphines are produced, exhibiting broad functional group compatibility. Further functionalization of the products under mild conditions renders the formed compounds useful building blocks.

Rhodium-catalyzed C7-selective decarbonylative arylation, olefination, and methylation of indoles with carboxylic acids or anhydrides by C-H and C-C bond activation have been developed. Furthermore, C7-acylation products can also be generated selectively at a lower reaction temperature in the developed system. The key to the high reactivity and regioselectivity of this transformation is the appropriate choice of an indole N-PtBu2 chelation-assisted group. This method has many advantages, including easy access and removal of the directing group, the use of cheap and widely available coupling agents, no requirement of an external ligand or oxidant, a broad substrate scope, high efficiency, and the formation of a sole regioisomer.

An efficient method for the metal-free deaminative borylation of alkylamines, using bis(catecholato)diboron as the boron source, to directly synthesize various alkyl potassium trifluoroborate salts is introduced. The key to this high reactivity is the utilization of pyridinium salt activated alkylamines, with a catalytic amount of a bipyridine-type Lewis base as a promoter. This transformation shows good functional-group compatibility (e.g., it is unimpeded by the presence of a ketone, indole, internal alkene, or unactivated alkyl chloride) and can serve as a powerful synthetic tool for borylation of amine groups in complex compounds. Mechanistic experiments and computations suggest a mechanism in which the Lewis base activated B2 cat2 unit intercepts an alkyl radical generated by single-electron transfer (SET) from a boron-based reductant.

Multi-borylated compounds are useful starting materials for the construction of complex molecules. Although certain classes of multi-borylated compounds, such as geminal and 1,2-bis(boronates), can now be accessed selectively by several well-established methods, the synthesis of one class—those containing more than two boronate substituents—remains a great challenge. Here, copper catalytic systems were developed for the borylation of gem-difluoroalkenes with B2pin2 via dual C–F bond activation to afford multi-borylate libraries—1,2-alkyldiboronates, 1,1,2-alkyltriboronates and 1,1,1,2-alkyltetraboronates—by slightly tuning the reaction conditions. The advantages of this strategy include not only avoiding the use of different methods and substrates for each type of multi-substituted alkyl boronate, but also the excellent functional group compatibility, readily accessible gem-difluorovinyl group and highly chemoselective process. Organoboron compounds are versatile intermediates in organic chemistry, and as such the selective introduction of multiple boron-containing groups is of high interest. Here Shi and co-workers report a copper-catalysed method that can selectively introduce two, three or four boronate groups into common starting materials by simply making minor modifications to the reaction conditions.

Summary gem-Difluoroalkenes have steric and electronic profiles similar to those of ketones, aldehydes, and esters, and consequently have been used widely as carbonyl isosteres in modern drug discovery. Although many attempts have been made to achieve gem-difluoroalkenes, the induction of enantioselectivity at the α position of a gem-difluorovinyl group still remains a challenge. Herein, an efficient method for the construction of gem-difluoroallylboronates with high enantiomeric excess via a copper-catalyzed defluoroborylation of 1-(trifluoromethyl)alkenes with B2pin2 is described. The reaction conditions were mild, and a variety of common functional groups, such as ether, fluoride, chloride, bromide, iodide, ester, cyano, sulfide, amino, and indoyl groups, were well tolerated. Furthermore, we not only applied this developed system as a powerful synthetic tool for the late-stage modification of complex compounds but also highlighted the utility of the formed compounds in synthesis.

A straightforward method was developed for construction of aromatic compounds with a triphenylene core. The method involves Pd-catalyzed annulative dimerization of o-iodobiaryl compounds by double C-I and C-H bond cleavage steps. Simple reaction conditions are needed, requiring neither a ligand nor an oxidant, and the reaction tolerates a wide range of coupling partners without compromising efficiency or scalability. Significantly, the tetrachloro-substituted synthon, 1,6,11-trichloro-4-(4-chlorophenyl)triphenylene, can be generated and used to prepare a series of fully fused, small graphene nanoribbons by a late-stage arylation with arylboronic acids and a subsequent Scholl reaction. The synthetic strategy enables bottom-up access to extended π-systems in a controlled manner.

Recent advances in transition metal-catalyzed selective C-H functionalization of indoles have garnered tremendous attention. Great efforts have been devoted to C2 and C3 arylation because of the inherent reactivity of the pyrrole ring. Until recently, elegant methods have been developed to enable selective direct arylation on the benzenoid moiety at C4, C5, C6, and C7. This review highlights the contributions made in benzenoid direct arylation of indoles and presents their potential in organic synthesis.

A novel rearrangement of cycloketoxime esters to cyano-containing benzoates beyond the traditional Beckmann and Neber rearrangement process has been established in the presence of photocatalysis catalysis. This SET-induced structural reorganization of cycloketoxime esters is perfectly an atom economic process and distinguished by mild and safe reaction conditions that avoid acid, base and toxic cyanide salts.

Correction for ‘Rhodium-catalysed selective C–C bond activation and borylation of cyclopropanes’ by Yandong Wang et al., Chem. Sci., 2021, DOI: 10.1039/d0sc06186g.

Carbon dioxide (CO2) capture and transformation are important for continuously increasing concentration of atmospheric CO2. To effectively capture CO2 and further fix it into valuable chemical products, functionalized dynamic metal−organic frameworks (MOFs) have been utilized not only because of their inherent cavity for accommodating CO2 but also due to their reversible structural transformation responsible for external stimuli for regulating the reaction. Herein, we report a dynamic and functional MOF [Cd3(L)2(BDC)3]2*16DMF (MOF-1a) (DMF = N,N-dimethylformamide) achieved by reaction of amino tripodal imidazole ligand N1-(4-(1H-imidazol-1-yl)benzyl)-N1-(2-aminoethyl)ethane-1,2-diamine (L) and 1,4-benzenedicarboxylic acid (H2BDC) with cadmium salt. MOF-1a not only shows unprecedented high catalytic activity [initial turnover number (TON) up to 9300] and broad substrate scope for the carboxylative cyclization of propargylamines with CO2, but also can be switched on and off upon reversible structural transformation due to its dynamic 5-fold interpenetrating structure. Further studies demonstrate that MOF-1a shows selective catalytic property depending on the size of substrates, like an imitation of sophisticated biological system.

An efficient enantioselective protocol has been reported to build highly oxygenated and densely substituted bicyclo[m.n.1] skeletons through intramolecular asymmetric α-arylative desymmetrization of 1,3-diketones. Employing Pd catalyst and FOXAP ligand, various bicyclo[m.n.1] skeleton with different size can be accessed with high enantio- and diastereoselectivities. Utilizing the present method as a key step, formal asymmetric total synthesis of the (-)-parvifoline has been demonstrated.

An effective and practical strategy has been established for the direct and site-selective arylation of indoles at the C4 and C5 positions with the aid of a readily accessible, cheap, and removable pivaloyl directing group at the C3 position. This transformation shows good functional-group tolerance and could serve as a powerful synthetic tool for the synthesis of medicinally relevant compounds. This method and those developed in previous research together enable the regiocontrolled direct arylation of indole at each C-H bond without prefunctionalization of the reactive sites.

Preparative electrochemical synthesis is an ideal method for establishing green, sustainable processes. The major benefits of an electro-organic strategy over that of conventional chemical synthesis are the avoidance of reagent waste and mild reaction conditions. Here, an intermolecular cross-dehydrogenative coupling between phenols and β-dicarbonyl compounds has been developed to build various benzofurans under undivided electrolytic conditions. Neither transition metals nor external chemical oxidants are required to facilitate the dehydrogenation and dehydration processes. The key factor in success was the use of nBu4 NBF4 as the electrolyte and hexafluoroisopropanol as the solvent, which play key roles in the cyclocondensation step. This electrolysis is scalable and can be used as a key step in drug synthesis. On the basis of several experimental results, the mechanism, particularly of the remarkable anodic oxidation and cyclization process, was illustrated.

A practical single-electron-transfer-induced selective C(sp

Organoboron reagents are important synthetic intermediates that have a key role in the construction of natural products, pharmaceuticals and organic materials

A rhodium-catalyzed system is introduced for in situ modification of biaryl-type monophosphines with hydrosilanes through a PIII -chelation-assisted dehydrogenative silylation reaction. A series of ligands containing silyl groups with different steric and electronic properties were obtained with excellent regioselectivities. This method offers many advantages, including the use of commercially available phosphines, no requirement for an external ligand or oxidant, a broader substrate scope, high efficiency, and access to a single regioisomer. Based on the outstanding properties of the parent scaffolds, the silyl-substituted phosphines serve as excellent ligands in Pd-catalyzed asymmetric Suzuki coupling reactions.

A series of in situ formed alkenyl diboronate complexes from alkenyl Grignard reagents (commercially available or prepared from alkenyl bromides and Mg) with B2 Pin2 (bis(pinacolato)diboron) react with diverse alkyl halides by a Ru photocatalyst to give various gem-bis(boryl)alkanes. Alkyl radicals add efficiently to the alkenyl diboronate complexes, and the adduct radical anions undergo radical-polar crossover, specifically, a 1,2-boryl-anion shift from boron to the α-carbon sp2 center. This transformation shows good functional-group compatibility and can serve as a powerful synthetic tool for late-stage functionalization in complex compounds. Measurements of the quantum yield reveal that a radical-chain mechanism is operative in which the alkenyl diboronates acts as reductive quencher for the excited state of the photocatalyst.

The nickel-catalyzed direct borylation and silylation of phenolic esters has been established. The key to this highly efficient acyl C–O bond borylative and silylative cleavage depends on the appropriate choice of different ligands and additives in the presence of nickel catalyst. Both transformations exhibit good functional group compatibility and can serve as powerful synthetic tools for late-stage functionalization of complex compounds. The elucidation of key mechanistic features of this newly developed acyl C–O bond activation in esters was confirmed by two well-characterized organonickel(II) intermediates.

A nickel/N-heterocyclic carbene catalytic system has been established for decarbonylative borylation of amides with B2 nep2 by C-N bond activation. This transformation shows good functional-group compatibility and can serve as a powerful synthetic tool for late-stage borylation of amide groups in complex compounds. More importantly, as a key intermediate, the structure of an acyl nickel complex was first confirmed by X-ray analysis. Furthermore, the decarbonylative process was also observed. These findings confirm the key mechanistic features of the acyl C-N bond activation process.

We report a regioselective direct arylation of indoles at the C7 position with (hetero)aryl bromides., The indole scaffold will continue to play a vital role in the future of drug discovery and agrochemical development. Regioselective direct arylation of indoles on the benzenoid moiety is a challenging task due to the inherent reactivity of the C2 and C3 positions. Here, we have developed an effective strategy for the regioselective direct arylation of indoles at the C7 position with (hetero)aryl bromides by the rational design of a directing group. The key to the high selectivity and reactivity of this method is the appropriate selection of a class of directing groups, N-PR2 (R = tBu and cHex), that are easily removed in the presence of the Wilkinson’s catalyst. Using the present method as a key step, formal synthesis of marine alkaloid dictyodendrin B has also been demonstrated.

Transition-metal-mediated metalation of an aromatic C-H bond that is adjacent to a tertiary phosphine group in arylphosphines via a four-membered chelate ring was first discovered in 1968. Herein, we overcome a long-standing problem with the ortho-C-H activation of arylphosphines in a catalytic fashion. In particular, we developed a rhodium-catalyzed ortho-selective C-H borylation of various commercially available arylphosphines with B

Rhodium-catalyzed C7-selective decarbonylative arylation, olefination, and methylation of indoles with carboxylic acids or anhydrides by C-H and C-C bond activation have been developed. Furthermore, C7-acylation products can also be generated selectively at a lower reaction temperature in the developed system. The key to the high reactivity and regioselectivity of this transformation is the appropriate choice of an indole N-PtBu

Different site selectivities have been reported for indoles with different directing groups in copper-catalyzed site-selective C-H arylations. Computational and mass spectrometric studies have been conducted in an effort to understand the origin of site selectivity and the effects of the directing groups. A Heck-like mechanism involving a four-membered ring is found in all three of the cases studied. For N-acetyl indole with a weak directing group, a neutral Heck-like mechanism is controlled by an electronic effect resulting in C2 site selectivity. In contrast, indole with a N-P(O) tBu2 group and N-benzyl-3-pivaloyl indole prefer a cationic Heck-like reaction in which a favorable six-membered chelation between the directing group and the CuIII center determines the C6 and C5 site selectivities.