Indoles In Good Yields Research Articles

Highly Diastereo‐ and Enantioselective Synthesis of Cyclohepta[b]indoles by Chiral‐Phosphoric‐Acid‐Catalyzed (4+3) Cycloaddition

AbstractA highly enantio‐ and diastereoselective formal (4+3) cycloaddition of 1,3‐diene‐1‐carbamates with 3‐indolylmethanols in the presence of a chiral phosphoric acid catalyst is reported. The approach described herein provides efficient access to 6‐aminotetrahydrocyclohepta[b]indoles in good yields with mostly complete diastereoselectivity and excellent levels of enantioselectivity (>98:2 dr and up to 98 % ee). Mild reaction conditions, facile scale‐up, and versatile derivatization highlight the practicality of this methodology. A mechanistic study suggests that cycloaddition occurs in a stepwise fashion, after the formation of an ion pair between the chiral catalytic phosphate and the intermediate carbocation.

Cleavage of C–C Bonds for the Synthesis of C2-Substituted Quinolines and Indoles by Catalyst-Controlled Tandem Annulation of 2-Vinylanilines and Alkynoates

The strategy for the synthesis of C2-substituted indoles and quinolines from 2-vinylanilines and alkynoates through C-C bond cleavage is developed. With these general methods, 2-substituted indoles and quinolines can be accessed via tandem Michael addition and cyclization with no requirement of oxidant. This strategy not only provides a method for the synthesis C2-substituted indoles in good yields through the simultaneous cleavage of C═C and C≡C bonds under metal-free conditions but also provides a simple method for the generation of the C2-substituted quinolines in moderate yields via Pd-catalyzed C≡C bond cleavage.

One-Pot MCR-Oxidation Approach toward Indole-Fused Heteroacenes.

A straightforward synthetic route toward indole-fused heteroacenes was developed. The strategy is composed of a one-pot process starting with a multicomponent reaction of cyclohexanone, primary amine and N-tosyl-3-nitroindole followed by an oxidation step. The one-pot approach was found to be general, affording both symmetric and nonsymmetric indolo[3,2-b]indoles in good yields. The strategy was also utilized for accessing 5-ring fused benzo[g]indolo[3,2-b]indole. We could extend the methodology for the synthesis of benzothieno[3,2-b]indoles starting from 3-nitrobenzothiophene. The importance of the developed method was exemplified by performing the reaction sequence on gram scale and also by the synthetic transformations of indolo[3,2-b]indoles. In addition, the change in photophysical properties with extension of conjugation of the synthesized heteroacenes was studied.

A Divergent Approach to Indoles and Oxazoles from Enamides by Directing-Group-Controlled Cu-Catalyzed Intramolecular C-H Amination and Alkoxylation.

A directing-group-controlled, copper-catalyzed divergent approach to indoles and oxazoles from enamides has been developed. The picolinamide-derived enamides undergo the intramolecular aromatic C-H amination in the presence of a Cu(OPiv)2 catalyst and an MnO2 oxidant to form the corresponding indoles in good yields. On the other hand, simpler aryl- or alkyl-substituted enamides are converted to the 2,4,5-trisubstituted oxazole frameworks via vinylic C-H alkoxylation under identical conditions. The copper catalysis can provide uniquely divergent access to indole and oxazole heteroaromatic cores of great importance in medicinal and material chemistry.

Iron‐Catalyzed Regioselective Synthesis of 3‐Arylindoles

AbstractAn interesting iron‐catalyzed synthesis of 3‐arylindoles from their corresponding nitrosoarenes and alkynes has been developed. By using iron(II) phthalocyanine as the catalyst precursor and CO as the reductant, broad range of nitrosoarenes and alkynes were transformed into the corresponding indoles in good yields with excellent functional groups tolerance. Remarkably, CO gas can be replaced by other reductants such as isopropanol as well.

Iron-Catalyzed 1,5-Enyne Cycloisomerization via 5-Endo-Dig Cyclization for the Synthesis of 3-(Inden-1-yl)indole Derivatives.

An Fe(OTf)3-catalyzed 1,5-enyne cycloisomerization via 5-endo-dig cyclization is described for the synthesis of 3-(1-indenyl)indole derivatives. Since a variety of 1,5-enynes are readily accessible via Heck-Suzuki coupling, this strategy provides a rapid and easy access to a wide range of highly substituted 3-(1-indenyl)indoles in good yields.

ChemInform Abstract: A Synthetic Route to Chiral Tetrahydropyrroloindoles via Ring Opening of Activated Aziridines with 2‐Bromoindoles Followed by Copper‐Catalyzed C—N Cyclization.

A new synthetic route to nonracemic tetrahydropyrrolo[2,3-b]indoles has been developed via SN2-type ring opening of enantiopure N-activated aziridines with 2-bromoindoles followed by copper-catalyzed C–N cyclization. A series of N-activated aziridines and 2-bromoindole derivatives with different substitution patterns were studied to afford the corresponding tetrahydropyrrolo[2,3-b]indoles in good yields and excellent ee (up to 99%). Highly substituted tetrahydropyrrolo[2,3-b]indole was synthesized as a single stereoisomer (de, ee >99%) from enantiopure trans-disubstituted aziridine.

Double C–H Functionalization of Indoles via Three-Component Reactions/CuCl2-Catalyzed Aerobic Dehydrogenative Coupling for the Synthesis of Polyfunctional Cyclopenta[b]indoles

A sequential Rh2(OAc)4-catalyzed multicomponent reaction and CuCl2-catalyzed postcyclization process is developed to build polyfunctional cyclopenta[b]indoles in good yields with high diastereoselectivities in an atom- and step-economic fashion. The key discovery in this process is the CuCl2-catalyzed intramolecular aerobic dehydrogenative Csp2–Csp2 cross-coupling of indole C2 with an enol functionality. Mechanistic studies including X-ray photoelectron spectroscopy analysis suggest that the catalytic cycle involves Cu(II) and Cu(I). This coupling reaction represents a unique example of aerobic Cu-catalyzed direct coupling of indoles with enols under mild conditions.

A Synthetic Route to Chiral Tetrahydropyrroloindoles via Ring Opening of Activated Aziridines with 2-Bromoindoles Followed by Copper-Catalyzed C-N Cyclization.

A new synthetic route to nonracemic tetrahydropyrrolo[2,3-b]indoles has been developed via SN2-type ring opening of enantiopure N-activated aziridines with 2-bromoindoles followed by copper-catalyzed C-N cyclization. A series of N-activated aziridines and 2-bromoindole derivatives with different substitution patterns were studied to afford the corresponding tetrahydropyrrolo[2,3-b]indoles in good yields and excellent ee (up to 99%). Highly substituted tetrahydropyrrolo[2,3-b]indole was synthesized as a single stereoisomer (de, ee >99%) from enantiopure trans-disubstituted aziridine.

Aminocatalyzed Cascade Synthesis of Enantioenriched 1,7‐Annulated Indoles from Indole‐7‐Carbaldehyde Derivatives and α,β‐Unsaturated Aldehydes

AbstractWe report herein a new cascade strategy for the enantioselective synthesis of 1,7‐annulated indoles based on iminium‐enamine activation. A careful study of the indole substitution pattern revealed that a chloro substituent at the C‐3 position was important to the implementation of the reaction. Employing a diphenylprolinol silyl ether catalyst, a range of 3‐chloro‐1H‐indole‐7‐carbaldehyde derivatives reacted with α,β‐unsaturated aldehydes to afford the corresponding 1,7‐annulated indoles in good yields (62–99%) and enantioselectivities (62–92%). Besides the fluorescence properties of the 1,7‐ring fused indoles prepared following our methodology, these compounds contain a useful set of functional groups which undergo various synthetic transformations.magnified image

5-Hydroxybenzo[g]indoles formation from oxa-aza[3.3.3]propellanes

Nucleophilic attack on the bridgehead carbon atoms of oxa-aza[3.3.3]propellanes is reported for the first time. This gives access to functionalized 5-hydroxybenzo[g]indoles in good yields under green conditions with an easy purification procedure.

Pseudopericyclic 1,5- versus Pericyclic 1,4- and 1,6-Electrocyclization in Electron-Poor 4-Aryl-2-azabuta-1,3-dienes: Indole Synthesis from 2H-Azirines and Diazo Compounds.

Transformations of 2-azabuta-1,3-dienes, formed in Rh2(OAc)4-catalyzed reactions of diazo carbonyl compounds with 2H-azirines, dramatically depend on the nature of substituents. 4,4-Diphenyl-2-azabuta-1,3-dienes with two electron-acceptor substituents at C(1) undergo thermal 1,5-cyclization to give indoles in good yields. The increase in electron-withdrawing ability of C(1)-substituents facilitates the reaction that proceeds via pseudopericyclic 1,5-electrocyclization of 2-azabutadiene into 7aH-indolium ylide followed by prototropic shift. 3,4-Diphenyl-2-azabuta-1,3-dienes, resulting from reaction of 2,3-diphenyl-2H-azirine and diazo compounds, do not produce indoles via 1,5-cyclization due to the trans-configuration of the 4-Ph-group and the nitrogen, but undergo 1,4-cyclization to 2,3-dihydroazetes. 1,6-Cyclization into 2H-1,4-oxazines with participation of the oxygen of ester or amide group at C(1) of corresponding 2-azabuta-1,3-dienes does not take place due to kinetic and thermodynamic reasons. Instead of this, 1,6-electrocyclization with participation of phenyl substituent at C(4) of the 2-azabuta-1,3-dienes, providing isoquinoline derivatives, can occur at elevated temperatures. The DFT-calculations (mPWB1K/6-31+G(d,p)) confirm the dependence of 2-azabuta-1,3-diene transformation type on the nature of substituents.

ChemInform Abstract: Pd(II)‐Catalyzed Ligand Controlled Synthesis of Methyl 1‐Benzyl‐1H‐indole‐3‐carboxylates and Bis(1‐benzyl‐1H‐indol‐3‐yl)methanones.

A simple change of ligand and solvent allows controlled, effective switching between cyclization–carbonylation and cyclization–carbonylation–cyclization-coupling (CCC-coupling) reactions of 2-alkynylanilines catalyzed by palladium(II). The use of a [Pd(tfa)2(box)] catalyst in iPrOH afforded symmetrical ketones bearing two indoles in good yields; replacing the catalyst and solvent with Pd(tfa)2 and DMSO–MeOH led to the formation of methyl 1-benzyl-1H-indole-3-carboxylates in good yields.

Palladium catalyzed addition of arylboronic acid or indole to nitriles: synthesis of aryl ketones

Aryl ketones can be synthesized conveniently by a palladium catalyzed addition of arylboronic acid to nitriles in aqueous triflic acid. This catalytic system was extended to the addition of unprotected indoles to nitriles under a slightly modified condition to produce 3-acyl indoles in good yields.

ChemInform Abstract: Studies on Electrophilic Cyclization of N‐(Buta‐2,3‐dienyl)amides with N‐Bromosuccinimide and Its Applications.

AbstractThe formed vinyl bromides can be converted to alkynes and vinyl indoles in good yields.

ChemInform Abstract: A Tandem Isomerization/Prins Strategy: Iridium(III)/Broensted Acid Cooperative Catalysis.

AbstractDifferent types of indoles containing aliphatic allyl ether side chains are investigated as substrates in a tandem isomerization/Prins‐cyclization sequence to give pyran fused indoles in good yields.

Asymmetric synthesis of 3,4-annulated indoles through an organocatalytic cascade approach

Indoles bearing Michael acceptors at the 4-position were engaged in organocatalytic enantioselective cascade reactions with enals. Careful optimisation of the reaction parameters overcame the inherent low reactivity of these substrates, rendering 3,4-ring fused indoles in good yields, excellent enantioselectivities and as single diastereoisomers.

ChemInform Abstract: A Facile Access to Substituted Indoles Utilizing Palladium Catalyzed Annulation under Microwave Enhanced Conditions.

AbstractA microwave promoted Pd‐catalyzed cyclocondensation of o‐iodoanilines with aliphatic aldehydes (I) is developed to give 3‐substituted indoles in good yields.

Syntheses of Spiro[cyclopent[3]ene‐1,3′‐indole]s and Tetrahydrocyclohepta[b]indoles from 2,3‐Disubstituted Indoles through Sigmatropic Rearrangement

AbstractA NaOH‐mediated protocol was developed for the syntheses of a series of 2′‐arylspiro[cyclopent[3]ene‐1,3′‐indole]s and 6‐alkyl‐5,6,7,10‐tetrahydrocyclohepta[b]indoles in good yields by cyclization through a sigmatropic rearrangement of suitable 2,3‐disubstituted indoles. These precursors that contain a 4‐chloro‐2‐butenyl side chain at the 3‐position were obtained as a mixture of (E) and (Z) isomers through the reactions of o‐alkynylanilines and 3,4‐dichloro‐1‐butene. The cyclization strategy is general, and both medicinally important scaffolds were achieved by changing the substituent at the 2‐position of methyl 3‐(4‐chlorobut‐2‐enyl)‐1H‐indole‐1‐carboxylate. The reaction likely proceeds through [1,3]‐ and [3,3]‐sigmatropic rearrangements of the vinylcyclopropane substituent of the indole intermediate.

Application of FeCl3/Diorganyl Diselenides to Cyclization of o-Alkynyl Anilines: Synthesis of 3-Organoselenyl-(N-methyl)indoles

In this manuscript we described the FeCl₃/diorganyl di­selenides promoted intramolecular cyclization of <i>o</i>-alkynyl anilines, as an alternative for the construction of functionalized 3-organoselenyl indoles. The cyclization reactions proceeded smoothly at room temperature in the presence of air giving the 3-organoselenyl indoles in good yields. Additionally, the 3-organo­selenyl indoles proved to be quite useful as synthetic intermediates for the construction of more functionalized indole units through a selenium–lithium exchange reaction followed by trapping the lithium intermediate with different electrophiles.