Synthesis of 2,4,5-Trisubstituted Thiazoles via Lawesson’s Reagent-Mediated Chemoselective Thionation–Cyclization of Functionalized Enamides

An efficient route to 2-phenyl/(2-thienyl)-5-(het)­aryl/(methylthio)-4-functionalized thiazoles via one-step chemoselective thionation–cyclization of highly functionalized enamides mediated by Lawesson’s reagent is reported. These enamide precursors are obtained by nucleophilic ring-opening of 2-phenyl/(2-thienyl)-4-[bis­(methylthio)/(methylthio)­(het)­arylmethylene]-5-oxazolones with alkoxides and a variety of primary aromatic/aliphatic amines or amino acid esters, leading to the introduction of an ester, an N-substituted carboxamide, or a peptide functionality in the 4-position of the product thiazoles

Synthesis of 2,4,5-Trisubstituted Thiazoles via Lawesson’s Reagent-Mediated Chemoselective Thionation–Cyclization of Functionalized Enamides

An efficient route to 2-phenyl/(2-thienyl)-5-(het)­aryl/(methylthio)-4-functionalized thiazoles via one-step chemoselective thionation–cyclization of highly functionalized enamides mediated by Lawesson’s reagent is reported. These enamide precursors are obtained by nucleophilic ring-opening of 2-phenyl/(2-thienyl)-4-[bis­(methylthio)/(methylthio)­(het)­arylmethylene]-5-oxazolones with alkoxides and a variety of primary aromatic/aliphatic amines or amino acid esters, leading to the introduction of an ester, an N-substituted carboxamide, or a peptide functionality in the 4-position of the product thiazoles

One-Pot Synthesis of 2,4,5-Trisubstituted Imidazoles via [2 + 2 + 1] Cycloannulation of 1,3-Bishet(aryl)-monothio-1,3-diketones, α‑Substituted Methylamines and Sodium Nitrite through α‑Nitrosation of Enaminones

An efficient one-pot synthesis of a series of diversely functionalized trisubstituted 4(5)­het­(aroyl)-2,5(4)-het­(aryl)/alkylimidazoles from readily available 1,3-bishet­(aryl)­monothio-1,3-diketones has been reported. This novel sequential one-pot, three step protocol, wherein three new carbon nitrogen bonds are formed in contiguous fashion, involves in situ generation of enaminones by reaction of monothio-1,3-diketones with α-substituted methylamines, followed by their α-nitrosation with sodium nitrite and subsequent base mediated intramolecular heterocyclization of the resulting α-hydroxyiminoimines to trisubstituted imidazoles in high yields under mild conditions. These newly prepared 4(5)-het­(aroyl)-5(4)-het­(aryl)/alkylimidazoles are shown to exist as tautomeric mixture, however, their subsequent alkylation with methyl iodide in the presence of potassium carbonate affords 1-<i>N</i>-methy-2,5-bishet­(aryl)-4-het­(aroyl)­imidazoles in highly regioselective fashion in most of the cases. Synthesis of few 4(5)-(2-hydroxyphenyl)-2,5(4)-substituted imidazoles, which are known to be good coordinating ligands, has also been reported. A probable mechanism for the formation of these imidazoles from hydroxyiminoimine intermediates has also been suggested

Sequential One-Pot Synthesis of Tri- and Tetrasubstituted Thiophenes and Fluorescent Push–Pull Thiophene Acrylates Involving (Het)aryl Dithioesters as Thiocarbonyl Precursors

An efficient, one-pot three component synthesis of highly functionalized tri- and tetrasubstituted thiophenes has been reported involving (het)­aryl dithioesters as thiocarbonyl precursors. Thus, sequential base mediated condensation of readily available (het)­aryl active methylene ketones with (het)­aryl dithioesters followed by <i>S</i>-alkylation of the resulting enethiolate salts with activated halomethylene compounds and concurrent intramolecular aldol-type condensation of <i>S</i>-alkylated compounds affords substituted thiophenes in excellent yields. The methodology has also been extended for the synthesis of highly fluorescent push–pull substituted thiophene-5-acrylates by using bromocrotonate as the activated methylene alkylating agent

One-Pot Synthesis of Functionalized Benzo[<i>b</i>]thiophenes and Their Hetero-Fused Analogues via Intramolecular Copper-Catalyzed S‑Arylation of In Situ Generated Enethiolates

An efficient one-pot synthesis of highly functionalized multisubstituted benzo­[<i>b</i>]­thiophenes and their hetero-fused analogues, such as thieno­[2,3-<i>b</i>]­thiophenes, indolo­[2,3-<i>b</i>]­thiophenes, and pyrazolo­[3,2-<i>c</i>]­thiophenes, has been reported. The overall strategy involves sequential base-mediated condensation of 2-bromohet­(aryl)­acetonitrile precursors with (het)­aryl/alkyl dithioesters or other thiocarbonyl species such as dimethyl trithiocarbonate, <i>S</i>-methyl xanthates, methyl <i>N</i>-imidazolyl dithioate, <i>N</i>-alkyl dithiocarbamate, and phenyl isothiocyanate, followed by intramolecular copper-catalyzed arylthiolation of in situ generated enethiolates, furnishing a broad range of 2-functionalized 3-cyanobenzo­[<i>b</i>]- and/hetero-fused thiophenes in high yields

Synthesis of 2‑Phenyl-4,5-Substituted Oxazoles by Copper-Catalyzed Intramolecular Cyclization of Functionalized Enamides

An efficient two-step synthesis of 2-phenyl-4,5-substituted oxazoles involving intramolecular copper-catalyzed cyclization of highly functionalized novel β-(methylthio)­enamides as the key step has been reported. These enamides are obtained by nucleophilic ring-opening of newly synthesized 4-[(methylthio)­hetero­(aryl)­methylene]-2-phenyl-5-oxazolone precursors by alkoxides, amines, amino acid esters and aryl/alkyl Grignard reagents, thus leading to the introduction of an ester, N-substituted carboxamide or acyl functionalities at 4-position of the product oxazoles. Synthesis of two naturally occurring 2,5-diaryloxazoles, i.e., texamine and uguenenazole, via two-step hydrolysis–decarboxylation of the corresponding 2,5-diaryloxazole-4-carboxylates has also been described. Similarly, three of the serine-derived oxazole-4-carboxamides were elaborated to novel trisubstituted 4,2′-bisoxazoles through DAST/DBU-mediated cyclodehydration–dehydrohalogenation sequence. The present protocol is complementary and an improvement to our previously reported silver carbonate-induced cyclization of β-bis­(methylthio)­enamides to 2-phenyl-5-(methylthio)-4-substituted oxazoles

Synthesis of N‑Functionalized/NH-Multisubstituted Indoles, Thienopyrroles, Pyrroloindoles, and Pyrazolopyrroles via Sequential One-Pot Base-Mediated and Copper-Catalyzed Inter- and Intramolecular Amination of 2‑[2-Bromo(het)aryl]-3-(het)aryl-3-(methylthio)acrylonitriles

A novel, efficient route to substituted 1-<i>N</i>-(het)­aryl/NH-2-(het)­aryl-3-cyanoindoles and related pyrrolo-fused heterocycles such as thienopyrroles, pyrroloindoles, and pyrazolopyrroles has been reported. The overall protocol involves sequential cycloamination of readily available 2-[2-bromo­(het)­aryl]-3-(het)­aryl-3-(methylthio)­acrylonitrile precursors with primary amines or amides via two key C–N bond-forming processes, one base-mediated intermolecular and the other Cu-catalyzed intramolecular arylamination leading to N(1)–C(2) and N(1)–C­(7a) bond formation, respectively, in a two-step one-pot procedure

Cyclocondensation of Arylhydrazines with 1,3-Bis(het)arylmonothio-1,3-diketones and 1,3-Bis(het)aryl-3-(methylthio)-2-propenones: Synthesis of 1‑Aryl-3,5-bis(het)arylpyrazoles with Complementary Regioselectivity

Two efficient highly regioselective routes for the synthesis of unsymmetrically substituted 1-aryl-3,5-bis­(het)­arylpyrazoles with complementary regioselectivity starting from active methylene ketones have been reported. In the first protocol, the newly synthesized 1,3-bis­(het)­aryl-monothio-1,3-diketone precursors (prepared by condensation of active methylene ketones with het­(aryl) dithioesters in the presence of sodium hydride) were reacted with arylhydrazines in refluxing ethanol under neutral conditions, furnishing 1-aryl-3,5-bis­(het)­arylpyrazoles <b>7</b>, in which the het­(aryl) moiety attached to the thiocarbonyl group of monothio-1,3-diketones is installed at the 3-position. In the second method, the corresponding 3-(methylthio)-1,3-bis­(het)­aryl-2-propenones (prepared in situ by base-induced alkylation of 1,3-monothiodiketones) were condensed with arylhydrazines in the presence of potassium <i>tert</i>-butoxide in refluxing <i>tert</i>-butyl alcohol, yielding 1-aryl-3,5-bis­(het)­arylpyrazoles <b>9</b> with complementary regioselectivity (method A). The efficiency of this protocol was further improved by developing a one-pot, three-component procedure for the synthesis of pyrazoles <b>9</b>, directly from active methylene ketones, by reacting in situ generated 3-(methylthio)-1,3-bis­(het)­aryl-2-propenones with arylhydrazines in the presence of sodium hydride (instead of potassium <i>tert-</i>butoxide as base). The structures and regiochemistry of newly synthesized pyrazoles were confirmed from their spectral and analytical data along with X-ray crystallographic data of three pairs of regioisomers