8 research outputs found
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)Âaryl/(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-[bisÂ(methylthio)/(methylthio)Â(het)Âarylmethylene]-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)Âaryl/(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-[bisÂ(methylthio)/(methylthio)Â(het)Âarylmethylene]-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)ÂhetÂ(aroyl)-2,5(4)-hetÂ(aryl)/alkylimidazoles from
readily available 1,3-bishetÂ(aryl)Âmonothio-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)-hetÂ(aroyl)-5(4)-hetÂ(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-bishetÂ(aryl)-4-hetÂ(aroyl)Âimidazoles
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)Âaryl
dithioesters as thiocarbonyl precursors. Thus, sequential base mediated
condensation of readily available (het)Âaryl active methylene ketones
with (het)Âaryl 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
benzoÂ[<i>b</i>]Âthiophenes and their hetero-fused analogues,
such as thienoÂ[2,3-<i>b</i>]Âthiophenes, indoloÂ[2,3-<i>b</i>]Âthiophenes, and pyrazoloÂ[3,2-<i>c</i>]Âthiophenes,
has been reported. The overall strategy involves sequential base-mediated
condensation of 2-bromohetÂ(aryl)Âacetonitrile precursors with (het)Âaryl/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-cyanobenzoÂ[<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)Âenamides as the key step has been reported.
These enamides are obtained by nucleophilic ring-opening of newly
synthesized 4-[(methylthio)ÂheteroÂ(aryl)Âmethylene]-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-bisÂ(methylthio)Âenamides
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)Âaryl/NH-2-(het)Âaryl-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-bromoÂ(het)Âaryl]-3-(het)Âaryl-3-(methylthio)Âacrylonitrile
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)–CÂ(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-bisÂ(het)Âarylpyrazoles with complementary regioselectivity
starting from active methylene ketones have been reported. In the
first protocol, the newly synthesized 1,3-bisÂ(het)Âaryl-monothio-1,3-diketone
precursors (prepared by condensation of active methylene ketones with
hetÂ(aryl) dithioesters in the presence of sodium hydride) were reacted
with arylhydrazines in refluxing ethanol under neutral conditions,
furnishing 1-aryl-3,5-bisÂ(het)Âarylpyrazoles <b>7</b>, in which
the hetÂ(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-bisÂ(het)Âaryl-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-bisÂ(het)Âarylpyrazoles <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-bisÂ(het)Âaryl-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