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A highly enantioselective Pd/Bim-catalyzed dearomative Michael reaction applying polycyclic tropones as non-benzenoid aromatic Michael acceptors and arylboronic acids as aryl pronucleophiles has been developed. The bridged biaryls bearing central and axial chirality, including pentacyclic cyclohepta[b]indoles and 6,7-dihydrodibenzo- [a,c][7]annulen-5-ones, are generally generated in good to high yields and excellent enantioselectivities and can be readily transformed into useful derivatives. [ABSTRACT FROM AUTHOR]

A silver-catalyzed chemoselective cascade nucleophilic addition of a P-centered anion to isocyanides and cyclization reaction was developed for the efficient and practical synthesis of a wide range of 2-phosphinoyl indole and indol-3-ol derivatives. Unlike the well-documented synthesis of phosphorus-functionalized heterocycles via a P-centered radical, an anionic reactivity profile of phosphine oxides is most likely involved in this domino transformation. [ABSTRACT FROM AUTHOR]

Quinolines are biologically and pharmaceutically important N-heterocyclic aromatic compounds, which have broad applications in medicinal chemistry. Thus, their efficient synthesis has attracted extensive attention, and a broad range of synthetic strategies have been established. Of note, gold-catalyzed methodologies for the synthesis of quinolines have greatly advanced this field. Various gold-catalyzed intermolecular annulation reactions, such as annulations of aniline derivatives with carbonyl compounds or alkynes, annulations of anthranils with alkynes, and annulations based on A3-coupling reactions, as well as intramolecular cyclization reactions of azide-tethered alkynes, 1,2-diphenylethynes, and 2-ethynyl N-aryl indoles, have been developed. This review provides an overview of this exciting research area. Typical achievements in reaction methodologies and plausible reaction mechanisms are summarized. [ABSTRACT FROM AUTHOR]

We report an efficient site-selective synthetic method to C2 and C3 indanyl-substituted indole derivatives via 1,3-dithianyl induced Nazarov-type cyclization. In particular, C2-selective indanyl-substituted indoles were directly obtained by a BF3·Et2O-promoted sequence of intramolecular C3–C2 migration and Nazarov-type cyclization process. [ABSTRACT FROM AUTHOR]

Pyrrolo[1,2-a]indoles are structurally important scaffolds in many natural products and bioactive compounds. Herein, we report a novel synthetic method for pyrrolo[1,2-a]indole derivatives through visible-light-induced cascade dearomatizative cyclization of indoles with external nucleophiles. Moderate yields, good diastereoselectivities, and excellent regioselectivities were generally observed with the resultant indole-fused polycyclic compounds. [ABSTRACT FROM AUTHOR]

We report an innovative synthetic strategy for the generation of polysubstituted indoles from indolines, aryldiazonium salts, and azoles. The methodology encompasses an electrophilic substitution reaction affording C5-indoline intermediates which undergo an iodine-mediated oxidative transformation coupled with C–H functionalization to yield the indole derivatives. [ABSTRACT FROM AUTHOR]

A directing-group-free strategy for oxidative regioselective aminochalcogenation of indolines with amines and dichalconides is presented. This strategy combines tandem coupling sequences and oxidative dehydrogenation methods in a multi-component reaction, enabling the fast construction of a series of C2,3- or C2,5-aminochalcogenated indole derivatives. Moreover, the application of this synthetic approach is demonstrated through the late-stage modification of pharmaceuticals and the derivatization of the products, highlighting its potential and significance. [ABSTRACT FROM AUTHOR]

A highly regio- and chemoselective three-component assembling of N-pyrimidyl indoles with dienes and formaldehyde in the presence of a Co(III) catalyst was demonstrated. The scope of the reaction was investigated with a variety of indole derivatives to synthesize substituted homoallylic alcohols. Both butadiene and isoprene units were compatible with the reaction. To understand the reaction mechanism, various investigations were carried out, and suggested the plausibility of a reaction mechanism involving C–H bond activation as a key step. [ABSTRACT FROM AUTHOR]

An N-heterocyclic carbene (NHC) catalyzed enantio- and diastereoselective [12+2] cycloaddition is disclosed to rapidly construct sophisticated molecules bearing a tricyclic core and morpholine moiety. The success of our reaction relies on the NHC-catalyzed remote sp3 (C–H) bond activation of a 5H-benzo[a]pyrrolizine-3-carbaldehyde under oxidative conditions. Preliminary studies revealed that our products exhibit superior in vitro bioactivities against two plant pathogens to commercial Bismerthiazol (BT) and Thiodiazole Copper (TC). [ABSTRACT FROM AUTHOR]

A mild, palladium-catalyzed domino Heck-cyclization/alkoxylation sequence of aryl halide tethered allenamides is described, providing regiodivergent indole and indoline derivatives controlled by the N-protecting group. This room temperature reaction provided a functionalizable olefinic moiety with broad substrate scope. Preliminary mechanistic studies support the rearrangement of an indoline-derived intermediate to indoles with the N-acetyl allenamides forming free (NH) indoles. [ABSTRACT FROM AUTHOR]

An asymmetric Michael/hemiketalization reaction between isatin-derived β,γ-unsaturated α-ketoesters and 4-hydroxycoumarins was developed in aqueous media. A series of chiral spirooxindole derivatives with an all-carbon quaternary stereogenic center were obtained in high yields (up to 93%) and excellent enantioselectivities (up to 98%). [ABSTRACT FROM AUTHOR]

A general and efficient Cp*CoIII-catalyzed C2-alkylation of N-pyridylindoles has been achieved utilizing cyclopropanols as an alkylating reagent. Employing the developed method, diverse C2-alkylated indoles were accomplished in good yield. Additionally, the synthesized C2-alkylated indoles were utilized for the construction of tetrahydrocyclopenta-[b]indole, and 2-(3,3-arylallyl)-1-(pyridin-2-yl)-1H-indoles. Additionally, a plausible mechanism was also proposed. [ABSTRACT FROM AUTHOR]

A new method for the synthesis of azaaromatic vinylcyclopropanes (VCPs) has been disclosed in this paper by using pyrrole or indole derivatives as nucleophilic reagents to react with vinylidenecyclopropane-diesters (VDCP-diesters) in the presence of a Pd catalyst, a phosphine ligand and a base under mild conditions in up to 98% yield with a reasonable substrate scope. This reaction is one of the few examples of hydroamination at electron-rich allene's β-position. A plausible reaction mechanism has also been proposed through a zwitterionic π-propargyl N-palladium species according to the previous work and the obtained deuterium labeling experimental result. [ABSTRACT FROM AUTHOR]

A straightforward approach to the synthesis of 3-bromoindoles via palladium-catalyzed oxidative C–H activation/annulation of N-alkylanilines with bromoalkynes has been described. This protocol features high atom economy, excellent chemo- and regioselectivities, and good functional group tolerance. Moreover, the resultant 3-bromoindoles can be transformed to various functionalized indole derivatives, which demonstrates the practicability of this method in organic synthesis. [ABSTRACT FROM AUTHOR]

3-Acylindole motifs are wildly found in pharmaceuticals and biologically active alkaloids. Synthesis of this motif from aldehydes and indoles via dehydrogenative cross-coupling (CDC) reactions is the most efficient pathway. Here, we report a method for synthesis of 3-acyl indoles from aldehydes by a combination of photocatalysis and palladium catalysis. This mild, robust method is compatible with a wide array of functional groups and has a broad substrate scope. Our findings may inspire the development of new CDC reactions. [ABSTRACT FROM AUTHOR]

Redox-sensitive functionalities such as aliphatic amines with low oxidation potentials and easily oxidized by photocatalysts are generally not compatible with photocatalytic reactions. We describe a hydrogen-bond-assisted visible-light-mediated [2+2] cycloaddition of redox-sensitive aliphatic-amine-containing indole derivatives providing a range of cyclobutane-fused polycyclic indoline derivatives, especially bridged-cyclic indolines. Mechanistic studies indicated that the success of the reaction was based on on the formation of H-bonds between the N-atom and alcohol proton of TFE or HFIP, with this formation preventing or blocking the single-electron transfer from the aliphatic amine functionality to the excited photocatalyst. [ABSTRACT FROM AUTHOR]

We demonstrated γ-aminocyclopentenones to be a suitable surrogate for reactive cyclopentadienone via a pseudocine-substitution manifold. This approach enabled its orchestrated annulation with "tailored" bis-nucleophiles and to furnish complex β,γ-annulated cyclopentanoids or indole-based polycyclic architectures. This strategy represents a generalized means for direct, regioselective and stereoselective β,γ-functionalization of monosubstituted or unsubstituted aminocyclopentenones. [ABSTRACT FROM AUTHOR]

Regiodivergent formal [5+2]- and [4+2]-annulation reactions of indole derivatives with 2-(2-alkynyl)aryl cyclopropane-1,1-diesters (ACPs) have been developed. A series of tetracyclic indole derivatives were delivered in a 77% average yield with excellent regioselectivities enabled by Au(I)/Sc(III) bimetallic relay catalysis. A gram-scale reaction and further transformation of the resulting tetracyclic indoles demonstrated the practical utility of this protocol. Moreover, the photophysical properties of the obtained multicyclic compounds were also investigated. [ABSTRACT FROM AUTHOR]

Cu(II)-mediated C–H sulphenylation or selenylation of Trp indole by a derivative of cysteine or selenocysteine enables access to the tryptathionine unit or its selenium congener. The mechanism of these protocols, which allow macrocyclization of Trp-containing peptides, has been studied. [ABSTRACT FROM AUTHOR]

A stereoselective, copper-catalyzed, arene C(sp2)–H functionalization/Michael-type annulation reaction involving α-diazocarbonyl compounds has been developed. The method features low catalyst loadings, high yields, and excellent regio and stereoselectivity, in the synthesis of various heteroaromatic frameworks by employing indoles as the arene partner. [ABSTRACT FROM AUTHOR]

A general and efficient Cp*CoIII-catalyzed C2-thiolation and C2,C3-dithiolation of indole derivatives has been achieved employing N-(aryl/alkylthio)succinimide as a thiolating reagent. This external oxidant-free method utilizes only catalytic amounts of additive and tolerates various functional groups to afford various thiolated products in good yields. Control experiments revealed the importance of the Cp*CoIII-catalyst for both C2- and C3-thiolation. [ABSTRACT FROM AUTHOR]

A strategy for one-pot synthesis of isoindoles is described via a catalytic multicomponent dehydrogenative annulation of diarylimines, vinyl ketones and simple amines. In the presence of a rhodium catalyst and Cu oxidant, four C–H and two N–H bonds are activated along with the formation of one new C–C and two new C–N bonds, leading to a series of isoindole derivatives in good to very high isolated yields. [ABSTRACT FROM AUTHOR]

The reaction of 2-alkenylanilines with SOCl2 in DMSO was found to selectively afford 3-unsubstituted indoles and 3-methylthioindoles. This switchable approach was found to be temperature-dependent: at room temperature, the reaction afforded 3-unsubstituted indoles through intramolecular cyclization and elimination; while at higher temperature, the reaction gave 3-methylthioindoles via further electrophilic methylthiolation. [ABSTRACT FROM AUTHOR]

A base-mediated transformation based on a designed intramolecular vinylogous Michael addition (intra-VMA) is presented to access 3-substituted 2-alkenyl indole derivatives. The reaction represents the first example of the intra-VMA for the construction of indoles. A one-pot N-allylation of ortho-tosylamidocinnamates/congeners with γ-bromocrotonates followed by intra-VMA has been described to provide access to a diverse range of 2-alkenyl indole derivatives in reasonable to high yields. The synthetic value of the developed intra-VMA has been demonstrated by gram-scale synthesis of a representative indole derivative and also by the formal synthesis of MK-7246: a Merck's clinical CRTH2 antagonist. [ABSTRACT FROM AUTHOR]

A nickel(II) catalyzed enantioselective thio-Claisen rearrangement of α-diazo pyrazoleamides with thioindoles was realized with modified chiral N,N′-dioxide ligands, affording a variety of C3-substituted indole derivatives in high yields (up to 95%) with excellent enantioselectivities (up to 96% ee) under mild reaction conditions. A possible transition state model was proposed based on previous reports and the X-ray crystal structure of the catalyst. [ABSTRACT FROM AUTHOR]

Herein, we report a protocol for visible-light-induced dearomative oxamination reactions of indole derivatives to afford functionalized spirocyclic products. These step-economical reactions, which involve C–N and C–O bond formation, feature mild conditions, a broad substrate scope, high yields, exclusive diastereoselectivity and step-economy. In addition, a similar protocol could be used to synthesize spirolactams by dearomative amidation of phenol derivatives. [ABSTRACT FROM AUTHOR]

A novel and efficient approach for the highly selective C-2 difluoromethylation of indole derivatives was developed by using sodium difluoromethylsulfinate (HCF2SO2Na) as the source of difluoromethyl groups and a Cu(II) complex as the catalyst. Various substrates were well tolerated in this transformation and the desired products were obtained in moderate to good yields. Moreover, the late-stage C-2 difluoromethylation of bioactive molecules containing an indole ring was achieved in good yields. Generally, this reaction features excellent functional group compatibility, broad substrate scope and excellent C-2 selectivity. [ABSTRACT FROM AUTHOR]

An efficient Rh/Pd relay catalyzed intermolecular and cascade intramolecular hydroamination for the synthesis of exclusive trans 1-indolyl dihydronaphthalenols (up to 88% yield, 99% ee) is described under mild conditions. Moreover, the in silico and in vitro screening showed that the novel 1-indolyl dihydronaphthalenol products are potent lead compounds for treating inflammation disease. [ABSTRACT FROM AUTHOR]

A process for the α-carboxyalkylation of tryptophols and tryptamines by the functionalization of C–H bonds under visible light irradiation has been developed. The photochemical strategy activated the C–Br bonds of α-bromo-alkylcarboxylic esters to provide carbon-centered radicals under the catalysis of Ir(III) photocatalyst and coupled with indole derivatives. This methodology displayed wide functional group tolerance and excellent regioselectivity, and was applied to the late-stage functionalization and preparation of indole-containing hybrids. [ABSTRACT FROM AUTHOR]

Traditionally, amines react with nitrosoarenes to provide the corresponding imines or azo compounds. Herein, we report an acid mediated annulation reaction of aliphatic amines and nitrosoarenes to provide indole derivatives. The elusive direct annulation of aliphatic amines and nitrosoarenes via simultaneous C–C and C–N bond formation was achieved under metal free conditions. This conceptually novel method for indole synthesis does not require pre-functionalization steps for the new C–C and C–N bond formation. The method has been applied for an elegant synthesis of nor-neocryptolepine and neocryptolepine. [ABSTRACT FROM AUTHOR]

An efficient Rh(III)-catalyzed straightforward strategy was developed for the tandem C4 arylamination/annulation of indole derivatives with anthranil to provide indoloquinoline moieties. This method is simple and regioselective with a wide scope and functional group tolerance. Mechanistic studies revealed the important role of the newly installed azacycle in the conversion of O-protected aldoximes to their cyano derivatives. Studies were carried out to explore the promising photophysical properties of the obtained indoloquinoline derivatives. [ABSTRACT FROM AUTHOR]

The first Pd-catalyzed direct C–H acylation of indoles at the C4 position with α-oxocarboxylic acids using a ketone directing group is described. This reaction exhibits high regioselectivity with the tolerance of a wide scope of functional groups to afford diverse acylated indoles in moderate-to-good yields. The control experiments evidence the generation of acyl radicals via K2S2O8 promoted decarboxylation of α-oxocarboxylic acids and the involvement of a PdII/PdIV catalytic cycle. Importantly, the synthetically useful selectivity observed might be applied to prepare indole derivatives with anti-tumor activity as tubulin inhibitors. [ABSTRACT FROM AUTHOR]

We herein report a rhodium(iii)-catalyzed cross coupling of indole derivatives with alkylidenecyclopropanes (ACPs) in the presence of KCl, affording the alkene products exclusively with E-selectivity via C–H bond activation. The beta-H elimination to afford the conjugated diene derivatives has been suppressed by the addition of KCl. A plausible reaction mechanism has been proposed along with derivatization of the obtained product to demonstrate the practical usefulness of this synthetic protocol. [ABSTRACT FROM AUTHOR]

A 1,3-iodo-amination with iodine reagent that involved the Csp2–Csp3 dual functionalization of 2-methyl indoles was developed to provide 2-aminomethyl-3-iodo-indole derivatives. The iodo-amination proceeded via a 1,4-transfer of an imide group through the formation of an indolyl(phenyl)iodonium imide using PhI(OAc)2, followed by an iodination using DIH or a double iodination of indole using excess DIH. [ABSTRACT FROM AUTHOR]

A highly enantioselective organocatalytic vinylogous Mukaiyama aldol reaction of silyloxy dienes and isatins under bifunctional organocatalysis is presented. Substituted 3-hydroxy-2-oxindoles are synthesised in good yields and enantioselectivities. These synthetic intermediates are used for the construction of more complex molecules with biological properties such as the formal synthesis of a CB2 agonist presented. [ABSTRACT FROM AUTHOR]

An unprecedented Rh-catalyzed C2-difluoroalkylation of indole derivatives with 2,2-difluorovinyl arenesulfonates has been reported. This reaction provides a rare instance of catalytic difluoroalkylation through hydroarylation of gem-difluoroalkenes. The sulfonate group works as a chelating ligand, thus stabilizing the rhodacycle intermediate, leading to the uncommon transformation. [ABSTRACT FROM AUTHOR]

A novel and expedient one-pot synthesis of thiazino[2,3,4-hi]indole derivatives from o-haloaryl enamines and o-bromothiophenols has been developed. The tandem oxidative coupling/heteroannulation reactions exhibit high selectivity and good efficiency. The polycyclic heterocyclic products obtained might be useful in medicinal chemistry and materials science. [ABSTRACT FROM AUTHOR]

We demonstrate that a simple cobalt complex can regioselectively couple epoxides and aziridines with alkenes to generate valuable homoallylic alcohols and amines. The intramolecular reaction exhibits complete atom economy and, in contrast to traditional Mizoroki–Heck reactions, does not require stoichiometric amounts of base. An indole derivative was also shown to be a suitable coupling partner. Finally, promising results regarding the development of an intermolecular process using both epoxides and aziridines are reported, as well as preliminary mechanistic studies suggesting a radical mechanism. [ABSTRACT FROM AUTHOR]

The dual character of benzoquinone is exploited for the synthesis of benzo[a]carbazole derivatives starting from 3-ethylindole derivatives. A diene is generated in situ from the 3-ethylindole derivative with the help of benzoquinone, where it acts as an oxidizing agent. Later it serves as a dienophile and participates in a Diels–Alder reaction with the diene to afford benzo[a]carbazole derivatives. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various articles within the issue on topics including transcription factor assays, peptoid nanosheets, and aerobic dearomative reaction of indole derivatives along with list of periodical editors including Polly Arnold, Xile Hu and Xi Zhang.

The synthesis of polysubstituted hexahydroindoles through trienamine-organocatalyzed cycloadditions of pyrrolidinyl dienals, prepared by palladium-catalyzed cycloisomerization, is reported. The cycloadditions of this novel class of dienals proceed with excellent levels of enantio- and diastereoselectivity, with the regioselectivity of cycloaddition with respect to the tethering ring readily tuned through design of the cycloisomerization substrate. This work culminates in the first examples of double-stereodifferentiating trienamine catalysis, where catalyst stereocontrol dominates facial selectivity in the cycloaddition, affording azacyclic products that are specifically functionalized at every position. [ABSTRACT FROM AUTHOR]

A gold(i)-catalysed hydroaminative/arylative cascade for the efficient synthesis of a variety of indole-fused skeletons has been developed. Factors controlling the catalyst loading required in these transformations involving 1,3-unsubstituted indole intermediates have been revealed, allowing isolation of an unprecedented 1,3-dimetallated 3H-indole gold complex characterized by X-ray diffraction. [ABSTRACT FROM AUTHOR]

A novel acceptor, (3E,7E)-3,7-bis(2-oxoindolin-3-ylidene)-5,7-dihydropyrrolo[2,3-f]indole-2,6(1H,3H)-dione, was reported. Donor–acceptor (D–A) polymer semiconductors using this new building block showed high ambipolar charge transport performance with hole and electron mobilities up to 0.19 and 0.09 cm2 V−1 s−1, respectively, in thin film transistors. [ABSTRACT FROM AUTHOR]

The first nickel-catalyzed method for the borylation of carbon–hydrogen bonds in arenes and indoles is described. The use of an N-heterocyclic carbene ligand is essential for an efficient reaction, with an N-cyclohexyl-substituted derivative being optimal. This method is readily applied to the gram scale synthesis of 2-borylindole. [ABSTRACT FROM AUTHOR]

An asymmetrical squaraine dye (Py-3) with its two electron-donating aryl groups directly linked to the electron-withdrawing squaric acid core possesses an ideal bandgap of 1.33 eV, together with an intense and broad absorption band in the range 550–950 nm. Hence, the resulting solution-processed solar cells display an impressive Jsc of 12.03 mA cm−2 and a PCE of 4.35%. [ABSTRACT FROM AUTHOR]

Guided by a biosynthetic hypothesis, a serendipitous total synthesis of yuremamine has resulted in its structural revision from the putative pyrroloindole (1) to the flavonoidal indole (2), which was initially proposed as a biosynthetic intermediate. [ABSTRACT FROM AUTHOR]

An asymmetrical squaraine dye (Py-3) with its two electron-donating aryl groups directly linked to the electron-withdrawing squaric acid core possesses an ideal bandgap of 1.33 eV, together with an intense and broad absorption band in the range 550–950 nm. Hence, the resulting solution-processed solar cells display an impressive Jsc of 12.03 mA cm−2 and a PCE of 4.35%. [ABSTRACT FROM AUTHOR]

A highly efficient intermolecular cascade dearomatization of substituted indoles with benzodithiolylium tetrafluoroborate has been developed. This reaction provides a novel strategy to synthesise C3 methyl-substituted pyrroloindolines and furoindolines under mild reaction conditions, the utility of which has been demonstrated by the synthesis of esermethol and physovenine in a highly concise manner. [ABSTRACT FROM AUTHOR]