Divergent synthesis of isoindolo[2,1-a]indole and indolo[1,2-a]indole through copper-catalysed C- and N-arylations

A simple and efficient synthetic route to both isoindolo[2,1-a]indole and its structural isomer indolo[1,2-a]indole skeletons is presented. The key steps of the strategy are based on copper-catalysed C_aryl-C and C_aryl-N bond formation reactions, respectively. Moreover, we report the first copper-mediated intramolecular C-H functionalisation of an indole.     

Enhanced efficiency of recyclable C3-symmetric cinchonine-squaramides in the asymmetric Friedel–Crafts reaction of indoles with alkyl trifluoropyruvate

The highly enantioselective Friedel–Crafts reaction of indoles with trifluoropyruvate catalyzed by a C₃-symmetric cinchonine-squaramide is reported. A wide variety of trifluoromethylated indole derivatives were obtained in high yields and with excellent enantioselectivities (99% and up to >99% ee). Moreover the C₃ catalyst can be easily recovered and was used five times.     

Total synthesis of maremycins A,B, C1/C2, D1, and D2

The total synthesis of maremycins A, B, C₁/C₂, D₁, and D₂ is achieved starting from the natural amino acids l-isoleucine and S-methyl-l-cysteine, in which the total synthesis of maremycins B, C₁/C₂, and D₂ is accomplished for the first time. The synthesis features a position-selective intramolecular bromination process for the synthesis of key chiral building block, a Pd-catalyzed indole synthesis for the preparation of (2S,3S)-β-methyltryptophan and hydroxylation of oxindoles by molecular oxygen. In addition, the protocol for conversion of maremycins A and B to maremycins C and D was improved.     

Efficient coupling of heteroaryl halides with arylboronic acids in the presence of a palladium-tetraphosphine catalyst

Cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane:·1/2[PdCl(C₃H₅)]₂ system catalyses the Suzuki cross-coupling of heteroaryl halides with a range of arylboronic acids with very high ratio substrate/catalyst in good yields. Substrates such as pyridines, quinolines, thiophenes, an indole, pyrimidines or a furane have been used successfully.     

Sonogashira cross-coupling reactions with heteroaryl halides in the presence of a tetraphosphine-palladium catalyst

Heteroaryl halides undergoes cross-couplings with alkynes in good yields in the presence of [PdCl(C₃H₅)]₂/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as catalyst. A variety of heteroaryl halides such as pyridines, quinolines, a pyrimidine, an indole, a thiophene, or a thiazole have been used successfully. The reaction also tolerates several alkynes such as phenylacetylene and a range of alk-1-ynols. Furthermore, this catalyst can be used at low loading with some substrates.     

Ring-methylation of pyrrole and indole using supercritical methanol

The ring-methylation of pyrrole or indole using supercritical methanol proceeded at 623 K without the further addition of catalysts. Pyrrole produced a mixture of unreacted pyrrole and mono-, di-, tri-, and tetra-methylpyrroles at the reaction time of 8 h. On the other hand, indole was selectively methylated at the C3 position to afford 3-methylindole in 79% yield at the reaction time of 5 h. The ring-methylation of indole using supercritical methanol was claimed to proceed via (1H-indol-3-yl)methanol. The conversion of indole to (1H-indol-3-yl)methanol would be achieved by the electrophilic aromatic substitution between the indol-1-ide (indole anion) and H₂C⁺–OH. The (1H-indol-3-yl)methanol must be reduced to 3-methylindole in the presence of supercritical methanol.     

Voacalgines A–E,new indole alkaloids from Voacanga grandifolia

Five new indole alkaloids, voacalgines A–E (1–5) consisting of a C-mavacurine type of skeleton with 2,3-dihydroxybenzoate moiety, a macroline-type of skeleton, or a macroline-type of skeleton with C₆ unit, were isolated from the bark of Voacanga grandifolia. Their relative structures were determined by means of NMR data. Voacalgine A showed moderate cell growth inhibitory activities against HL-60 and HCT116 cells.     

Malonate-type bis(oxazoline) ligands with sp hybridized bridge carbon: synthesis and application in Friedel-Crafts alkylation and allylic alkylation

A series of simple and new C₂-symmetric diphenylmethylidene malonate-type bis(oxazoline) ligands were synthesized and applied to the Friedel-Crafts reaction and allylic alkylation. The Cu(II) complex of ligand 4b bearing the benzyl group afforded good to excellent enantioselectivity for the F-C adducts (up to >99% ee) between indole and alkylidene malonate, and the palladium complex of ligand 4c bearing the phenyl group afforded excellent enantioselectivity (up to 94% ee) for the allylic alkylation product.     

Fischer indolization and its related compounds—VII : Development of abnormal fischer indolization of ortho-methoxyphenylhydrazone to provide a synthetic method for useful indole derivatives possessing an active methine group at C6 and novel 3,6′-biindole derivatives

Fischer indolization of ethyl pyruvate 2-methoxyphenylhydrazone (1) with p-toluene-sulfonic acid in benzene in the presence of an enolizable dicarbonyl or an indolic compound gave either an indole product having an active methine group at C₆ or a novel type of 3,6′-biindole compound. Structures of the products were established by NMR spectra and chemical evidence.     

(Z)‐2‐(1‐Benzyl‐5‐nitro‐1H‐indol‐3‐ylmethyl­ene)‐1‐aza­bicyclo­[2.2.2]octan‐3‐one

In the title compound, C₂₃H₂₁N₃O₃, the indole ring is planar and the phenyl ring of the benzyl group makes a dihedral angle with the best plane of the indole ring of 73.77 (4)°. The double bond connecting the aza­bicyclic and indole moieties has Z geometry.     

(E)‐2‐Methyl‐3‐(2‐methyl‐2‐nitro­vinyl)‐1H‐indole and (E)‐3‐(2‐methyl‐2‐nitro­vinyl)‐2‐phenyl‐1H‐indole

In the title compounds, C₁₂H₁₂N₂O₂, (I), and C₁₇H₁₄N₂O₂, (II), respectively, the indole rings are planar and the vinyl groups lie out of the indole planes, making dihedral angles of 33.48 (5) and 41.31 (8)°, respectively. In (II), the dihedral angle between the phenyl and indole ring planes is 32.06 (6)°. In both mol­ecules, the double bond connecting the methyl­nitro­vinyl group and the indole nucleus adopts an E configuration. Notwithstanding the differences in space group [C2/c for (I) and P2₁2₁2₁ for (II)], the mode of packing of compounds (I) and (II) is determined by similar inter­molecular N—H⋯O hydrogen‐bonding inter­actions, forming chains that run parallel to [101] in (I) and [001] in (II).     

Direct C2-trifluoromethylation of indole derivatives catalyzed by copper acetate

Direct C2-selective trifluoromethylation of indole derivatives was achieved with Togni’s hypervalent iodine reagent and CuOAc as a catalyst in MeOH under mild conditions, affording the desired C2-trifluoromethylated indoles in good yield (up to 90%).     

Enantioselective Friedel–Crafts alkylation of indoles with β,γ-unsaturated α-ketoesters catalyzed by new squaramide-linked bisoxazoline–Zn(OTf)2 complexes

Enantioselective Friedel–Crafts alkylation reactions of indoles with β,γ-unsaturated α-ketoesters catalyzed by novel chiral C₂-symmetric squaramide-linked bisoxazoline–Zn(OTf)₂ complexes were investigated. The corresponding indole ketoesters were obtained in good to excellent yields (up to 98%) and with high enantioselectivities (up to 94% ee). This is the first report on the use of chiral squaramide-linked bisoxazoline SQBOX in a catalytic enanitioselective Friedel–Crafts alkylation reaction.     

Synthesis, characterization and comparison of group 14 pyrrolides and indolides Ph3MX (M = Si, Ge, Sn; X = C4H4N, C8H6N)

The biologically important heterocycles pyrrole, C₄H₄N, and indole, C₈H₆N, ought to be useful as reagents in organic synthesis. Unfortunately, working with them has proved to be difficult because they tend to self-polymerize in solution, especially in the presence of acid catalysts. When the self-polymerization can be controlled, however, the pyrrole and indole units should provide an important route to selective N-metal binding, particularly when these ligands are activated by alkyl-lithium reagents. Using this approach, a general synthesis of the group 14 pyrrolides and indolides, Ph₃MX (M = Si, Ge, Sn; X = C₄H₄N, C₈H₆N), has been developed and the results are reported here. The compounds are formed as high-melting, white crystalline solids and have been characterized by ¹³C-, ²⁹Si- and ¹¹⁹Sn-NMR, Raman and electron-impact mass spectroscopy as well as elemental analysis. A single-crystal X-ray study of Ph₃Si(C₄H₄N) has shown that the compound is disordered in the tetragonal lattice, even at low temperature (100 K).     

Design,synthesis of novel N prenylated indole-3-carbazones and evaluation of in vitro cytotoxicity and 5-LOX inhibition activities

A series of novel N-1 and C-3 substituted indole derivatives (5a–f) were designed, synthesized and evaluated for their cytotoxic properties, viz Brine Shrimp Lethality Bioassay (BSLB) besides 5-Lipoxygenase (5-LOX) inhibitory activities through in vitro assays. Structure Activity Relation (SAR) studies showed that compound 5d with an LC₅₀ of 6.49 μM and 5c with an IC₅₀ of 33.69 μM were found to be interesting for cytotoxicity and 5-LOX inhibitory activity respectively.     

Four novel gelsedine-type oxindole alkaloids from Gelsemium elegans

Four new gelsedine-type oxindole alkaloids (1-4) were isolated from the leaves and branches of Gelsemium elegans, together with 10 known alkaloids. The structures of the new alkaloids were determined by spectroscopic analyses and partial synthesis from known compounds. Gelsecrotonidine (1), 14-hydroxygelsecrotonidine (2), and 11-methoxygelsecrotonidine (3) possess an additional C₂ unit with an acetic acid residue compared to gelsenicine-related monoterpenoid indole alkaloids. 14-Hydroxygelsedilam (4) is an 18,19-nor-type monoterpenoid indole alkaloid.     

Synthesis of pyrrole- and indole-containing nitropropanoates on the basis of β-heteryl-α-nitroacrylates

Synthetic approach to β-furyl- and β-thienyl-α-nitroacrylates was modified. It was established that these nitroethenes react with pyrrole, N-methylpyrrole, and substituted indole derivatives in the absence of catalyst to afford products of the alkylation of pyrrole C² and indole C³ reaction sites. A possibility of this reaction to proceed under “dry reaction” condition on a silicagel surface was shown.     

Use of a Modified Leimgruber–Batcho Reaction to Prepare 6‐Chloro‐5‐fluoroindole

Abstract

An efficient synthesis of the title indole, the heterocyclic core of the standard 5‐HT_2C receptor agonist Ro 60‐0175, via a modified Leimgruber–Batcho indole synthesis is presented. The process can be used to make >100 g quantities of the target indole.     

New thieno[3,2-b]indole conjugates with 5-(methylene)rhodanine-3-acetic acid in dye-sensitized solar cells

Five new dyes with D–π–A structure bearing 5-(methylene)-rhodanine-3-acetic acid as an acceptor-anchoring part and thieno[3,2-b]indole or benzo[g]thieno[3,2-b]indole as an electron-donating part were synthesized and applied as photosensitizers for dye-sensitized solar cells (DSSCs). In addition, thermal stability, optical and electrochemical properties of these dyes were investigated. The highest PCE value of 1.09% (J_sc = 3.01 mA cm^–2, V_oc = 0.53 V, FF = 0.69) was achieved for DSSC based on benzo[g]thieno[3,2-b]indole dye under AM 1.5G irradiation.     

Caulerpin

The crystal structure of caulerpin (di­methyl 6,13‐di­hydro­dibenzo­[b,i]­phenazine‐5,12‐di­carboxyl­ate, C₂₄H₁₈N₂O₄), an indole alkaloid, reported in space group Cc with an acute β angle, has been redetermined in the correct space group, C2/c. The mol­ecule has twofold crystallographic symmetry and is composed of two essentially planar indole groups fused to an eight‐membered cyclo­octatetraene ring which adopts a boat conformation. The molecular dimensions are normal. The structure is stabilized by intermolecular and intramolecular interactions involving the indole N—H atom and carbonyl O atom [N?O 3.211 (4) and 2.836 (4) Å].