Allylindation of 1H-indole-3-carboxaldehyde in the presence of azoles—revisited

The allylindation of 1H-indole-3-carboxaldehyde in the presence of azoles (e.g., pyrazoles and imidazole) under aqueous Barbier-like conditions was reinvestigated and improved. Some of the results were at variance with a previous report (Tetrahedron Lett.2003, 44, 2101).     

Synthesis of substituted 4-(3-alkyl-1,2,4-oxadiazol-5-ylmethyl)-3,4-dihydro-2H-1,4-benzoxazines and 4-(1H-benzimidazol-2-ylmethyl)-3,4-dihydro-2H-1,4-benzoxazines

Substituted 2H-1,4-benzoxazines were synthesized from substituted 2-amino phenols and 1,2-dibromoethane using K₂CO₃ in good to excellent yields. The cyclized products were further reacted with alkyl bromides to obtain the desired N-substituted 3,4-dihydro-2H-1,4-benzoxazines.     

Reactions of aromatic dithiols with diethyl 2-alkyl-2-(oxiran-2-ylmethyl)malonates

New sulfur-containing butano-4-lactones were synthesized by reaction of diethyl 2-alkyl-2-(oxiran-2-ylmethyl)malonates with biphenyl-4,4′-dithiol, (biphenyl-4,4′-diyl)dimethanethiol, and (2,4,6-trimethylbenzene-1,3-diyl)dimethanethiol. Opening of the oxirane ring in the initial ester followed the Krasuskii rule.     

Synthesis of sulfur-containing vicinal aminoalcohols on the basis of N-(oxiran-2-ylmethyl)amines

The reaction of (methanediyldibenzene-4,1-diyl)dimethanethiol, (oxydibenzene-4,1-diyl)dimethanethiol, biphenyl-4,4′-diyldimethanethiol with 1-(oxiran-2-ylmethyl)piperidine and N-(oxiran-2-ylmethyl)-N-ethylaniline afforded the corresponding sulfur-containing vicinal aminoalcohols resulting from the opening of the oxirane ring in keeping with Krasusky rule.     

A novel and facile synthesis of 2-(cyclohexylamino)-6,7-dihydro-3-aryl-1H-indole-4(5H)-ones via a one-pot multi-component reaction

A simple and efficient synthesis of 2-(cyclohexylamino)-6,7-dihydro-3-aryl-1H-indole-4(5H)-ones was achieved via a one-pot multi-component reaction of cyclohexyl isocyanide, an aldehyde, a 1,3-dicarbonyl compound, and ammonium acetate in the presence of a catalytic amount of KHSO₄ in acetonitrile.     

Formation of the same pyrimido[1,2-a]indoles from 1-(oxiran-2-ylmethyl)-1H-indole or [1,3]oxazolo[3,2-a]indole derivatives in its reactions with aromatic amines

Reactions of two isomers—2-chloro-1-(oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde or 2-(chloromethyl)-2,3-dihydro[1,3]oxazolo[3,2-a]indole-9-carbaldehyde with aromatic amines lead to the same products in both cases—hydrochlorides of pyrimido[1,2-a]indole derivatives containing two fragments of an amine per one part of the indole nucleus. Its structure was confirmed by X-ray analysis of the crystals base, obtained by alkali treatment of the reaction product (when aryl is 4-MeOC₆H₄).     

Three-Component Reaction of 1-(Oxyran-2-ylmethyl)-1 H -indole-3-carbaldehyde with CH-Acids and Amines

One-pot synthesis of 3-vinyl substituted indoles containing 1,2-amino alcohol fragment at the nitrogen atom was performed by the reactions of 1-(oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde with methylene-active compounds and amines.     

Regioselective synthesis of 3-aryl-5-(1H-indole-3-carbonyl)-4-hydroxyfuroic acids as potential insulin receptor activators

3-Methoxy-4-aryl-furan-2,5-dicarboxylic acid (8) is selectively converted into its C-5 methylester (6) by treatment with methyl chloroformate followed by decarboxylation in one flask. Acylation of the resulting half ester with a 7-substituted indole was performed under mild conditions to afford 3-aryl-5-(1H-indole-3-carbonyl)-4-methoxy-2-furoic acid (11). The synthetic utility of the resulting furoic acids as a skeleton in the synthesis of potential insulin receptor activators is established.     

Reactions of aromatic dithiols with allyl glycidyl ether and 4-(oxiran-2-ylmethyl)morpholine

A reaction of allyl glycidyl ether and 4-(oxiran-2-ylmethyl)morpholine with aromatic dithiols furnished new substituted sulfur-containing propan-2-ols. The oxirane ring opening upon the action of aromatic dithiols follows a classic version and obeys the Krasuskii rule. O-Acetyl derivatives of some propan-2-ols synthesized were obtained as well.     

A new methodology for the synthesis of 3-amino-1H-indole-2-carboxylates

A new methodology has been developed for the synthesis of 3-amino-1H-indole-2-carboxylates. 2-Aminobenzonitriles were protected as benzyl (2-cyanophenyl)carbamates and converted into corresponding glycinate esters using sodium hydride and bromoacetate esters. Sodium hydride efficiently promotes the addition of the glycinate α-carbon to the cyano group at low temperatures, resulting in the formation of the desired indole core with 3-amino and 2-carboxylate groups. This new methodology uses Pd–C mediated hydrogenolysis with molecular hydrogen, providing neutral conditions for removal of the N-carbamate protecting group. This methodology demonstrates good functional group tolerance towards a variety of substituents in the aromatic ring and ester groups. The overall yield of 3-amino-1H-indole-2-carboxylates obtained by this four-step methodology is at least 30% or higher with yields as high as 50% realised for three of the indoles investigated in this study.     

Pd-catalyzed amination of 6-halo-2-cyclopropyl-3-(pyridyl-3-ylmethyl) quinazolin-4(3H)-one

6-Halo-2-cyclopropyl-3-(pyridyl-3-ylmethyl) quinazolin-4(3H)-one derivatives have been synthesized and utilized for amination reactions with aryl, heteroaryl and alkyl amines. Optimization of reaction conditions with different catalysts, ligands, bases, and solvents was conducted. The combination of Pd₂(dba)₃ with DavePhos (L3) proved to be best for these conversions in the presence of NaO^tBu in 1,4-dioxane at 100 °C. The relative reactivities of 6-bromo and 6-chloro-2,3-disubstitued quinazolinones with p-toluidine were conducted and as anticipated the 6-bromo analogue was totally consumed and 6-chloro derivative was completely unreactive.     

Synthesis of 2-(phenoxymethyl)oxirane derivatives through unexpected rearrangement of oxiran-2-ylmethyl benzenesulfonates

The synthesis of 2-(phenoxymethyl)oxirane derivatives from oxiran-2-ylmethyl benzenesulfonates was developed through a base promoted rearrangement. A new C-O bond was formed along with the unexpected cleavage of C-S bond via this process. This unusual reaction was characterized with mild reaction conditions, high efficiency, and excellent functional group tolerance. A plausible reaction mechanism was proposed on the basis of experimental results and control experiments.     

Synthesis of substituted 3-(3-chloro-1H-pyrazol-5-yl)quinoxalin-2(1H)ones

Synthetic strategies to gain access to all four isomers of 3-(3-chloro-1H-pyrazol-5-yl)quinoxalin-2(1H)ones with monosubstituted benzo core (i.e., compounds 8a–d) are described. Preparation of these heterocyclic compounds succeeded starting from only two different substituted 2-nitroanilines (i.e., 3-methoxy- and 4-methoxy-2-nitroaniline) in three or five steps, respectively.     

Efficient synthesis and solid state analysis of 3-(1H-pyrrol-2-yl)quinoxalin-2(1H)-one and 2-(1H-pyrrol-2-yl)-1H-benzo[d]imidazole from pyrrolo-2-ylglyoxyl acid

The synthesis of new pyrrole-functionalized quinoxalines and benzimidazole is described. Our methodology involves the condensation between 2-oxo-2-(1H-pyrrol-2-yl)acetic acid and differently substituted 1,2-phenylene diamines. Depending on the substitution and on the reaction conditions, the synthesis leads to either the pyrrolyl-quinoxaline or -benzimidazole heterocycles. Further insights concerning the structural arrangement of the pyrrolyl-quinoxaline were obtained by solid state analysis, revealing an inverted pyrrole similar to that observed for 2,3-dipyrrolyl quinoxalines. This observation accounts for the fact that strong dipolar interactions or intermolecular H-bonds may govern the structural arrangement in the solid state.     

Synthesis of (Z)-1-benzylidene-3-(1H-indol-1-yl)-1H-indene-2,2(3H)-dicarbonitriles via three-component reaction of 2-alkynylbenzaldehyde, malononitrile, and indole

Three-component reaction of 2-alkynylbenzaldehyde, malononitrile, and indole under mild conditions is described, which generates the desired (Z)-1-benzylidene-3-(1H-indol-1-yl)-1H-indene-2,2(3H)-dicarbonitriles in moderate to good yields. This reaction proceeds smoothly with high selectivity. The tandem condensation, nucleophilic addition, and 5-exo-cyclization may be involved in the process.     

Multienzymatic preparation of (−)-[3-(oxiran-2-yl)phenyl]methanol and (−)-3-(oxiran-2-yl)benzoic acid

The cascade use of enzymatic activities allows for the preparation of enantiomerically pure epoxides. In particular, using whole-cell biocatalysts we can prepare both (?)-[3-(oxiran-2-yl)phenyl]methanol and (?)-3-(oxiran-2-yl)benzoic acid in one-pot, two or three steps procedure. The yield is quantitative and enantiomeric purity greater than 95%. The selected biocatalysts contain a styrene monoxygenase from Pseudomonas fluorescens ST and a naphthalene dihydrodiol dehydrogenase from P. fluorescens N3, cloned and expressed in Escherichia coli.     

Diastereoselective synthesis of (2S)-2-[(R)-1H-indol-3-yl(phenyl)methyl]-2,3-dihydro-1H-inden-1-one

Double asymmetric induction in Michael reactions has been studied. Enantioselective alkylation of a cyclic ketone (1-indanone) with α-phenyl-nor-gramine was carried out. The relative configuration of (2S^∗)-2-[(R^∗)-1H-indol-3-yl(phenyl)methyl]-2,3-dihydro-1H-inden-1-one was established by X-ray diffraction. The relative configuration of (R^∗,R^∗,S^∗)- and (S^∗,R^∗,S^∗)-2-1H-indol-3-yl(phenyl)methyl]-2,3-dihydro-1H-inden-1-ols was established by ¹H NMR studies.     

Novel syntheses of 3-anilino-pyrazin-2(1H)-ones and 3-anilino-quinoxalin-2-(1H)-ones via microwave-mediated Smiles rearrangement

In this Letter, we report a novel approach to the preparation of 3-anilino-pyrazin-2(1H)-ones and 3-anilino-quinoxalin-2(1H)-ones from the corresponding 3-halo pyrazin-2-amines and 3-haloquinoxalin-2-amines, using a microwave-mediated Smiles rearrangement.     

Efficient microwave-assisted synthesis of 1-(1H-indol-1-yl)-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents

New conazole antifungals, in the series of triazole alcohols 23a-d and 24a-e incorporating an indole moiety substituted at 5-position by halogens, a cyano or 4-methoxyphenyl group, have been synthesized by ring opening of corresponding oxiranes 15 and 16. These dihalogeno intermediates and their congeneers could be prepared in high yields by Corey-Chaykovsky reaction under microwave irradiation.