8 research outputs found
Synthesis of 2,5-Bis(hetero)aryl 4′-Substituted 4,5′-Bisoxazoles via Copper(I)-Catalyzed Domino Reactions of Activated Methylene Isocyanides with 2‑Phenyl- and 2‑(2-Thienyl)-4-[(aryl/heteroaryl)(methylthio)methylene]oxazol-5(4<i>H</i>)‑ones
An efficient straightforward synthesis
of 2,5,4′-trisubstituted
4,5′-bisoxazoles via copperÂ(I)-catalyzed domino reactions of
2-phenyl- and 2-(2-thienyl)-4-[(aryl/heteroaryl)Âmethylene]-5-oxazolones
with activated methylene isocyanides has been reported. The overall
domino process comprised of formation of one C–C and two C–O
bonds involves initial nucleophilic ring opening of oxazolones by
cupriomethylene isocyanides followed by sequential construction of
two oxazole rings in the presence of copper catalyst. The broad substrate
scope and excellent functional group compatibility of the reaction
has been demonstrated by employing a variety of heteroaryl- and aryl-substituted
oxazolones and activated methylene isocyanides, yielding bisoxazoles
with three potential points of diversity. A probable mechanism for
this novel copper-catalyzed domino process has been proposed
Synthesis of Thieno-Fused Five- and Six-Membered Nitrogen and Oxygen Heterocycles via Intramolecular Heteroannulation of 4,5-Substituted 3‑Amino or 3‑Hydroxy 2‑Functionalized Thiophenes
Diverse
general high-yield routes for novel thieno-fused five-
and six-membered nitrogen and oxygen heterocycles such as thienoÂ[3,2-<i>b</i>]Âpyrroles, thienoÂ[3,2-<i>b</i>]Âfurans, thienoÂ[3,2-<i>b</i>]Âindoles, thienoÂ[3,2-<i>b</i>]Âbenzofurans, thienoÂ[3,2-<i>b</i>]Âpyridine-5-ones, thienoÂ[3,2-<i>b</i>]Âpyran-5-ones,
thienoÂ[3,2-<i>b</i>]Âisoquinolin-5-ones, thienoÂ[3,2-<i>b</i>]Âchromen-5-ones, thienoÂ[3,2-<i>b</i>]Âquinolin-9-ones,
and thienoÂ[3,2-<i>b</i>]Âchromen-9-ones have been developed
via in situ or stepwise intramolecular heteroannulation of newly synthesized
4,5-substituted 3-amino- or 3-hydroxy 2-functionalized thiophenes.
These substituted 3-amino/hydroxythiophenes were readily obtained
in high yields from easily accessible precursors, in a sequential
one-pot process, by treatment of a range of (het)Âaryl/unsubstituted
acetonitriles or acetates with (het)Âaryl dithioesters in the presence
of LDA, followed by in situ alkylation–intramolecular condensation
of the resulting enethiolate salts with functionalized activated methylene
halides. The functionalized activated methylene halides employed in
these reactions for the synthesis of various thieno-fused heterocycles
were cinnamyl bromide, 2-bromobenzyl chloride, bromocrotonate, 2-(bromomethyl)Âbenzoate,
and 2-chlorophenacyl bromide. A few of the 4,5-substituted 3-amino/hydroxy-2-stryrylthiophenes
(or 2-acrylates) displayed strong fluorescence, and their absorption/emission
spectra have also been examined
Synthesis of 2,4,5-Trisubstituted Oxazoles with Complementary Regioselectivity from α‑Oxoketene Dithioacetals and β‑(Methylthio)-β-(het)aryl-2-propenones
An efficient protocol for the synthesis
of 2,5-substituted 4-acyloxazoles
and the related 2,4-substituted 5-acyloxazoles with complementary
regioselectivity from the corresponding α-oxoketene dithioacetals
or β-(het)Âaryl/(methylthio)Âenone precursors has been reported.
In the first protocol, the α-oxoketene dithioacetals or β-(methylthio)Âenones
were converted to the corresponding α-bromo-β-(methylthio)Âenones
followed by copper catalyzed inter/intramolecular annulation of these
intermediates with various primary amides affording 2-(het)Âaryl/alkyl-4-(het)Âaroyl-5-(methylthio)/(het)Âaryloxazoles
via concomitant formation of the C4–N and C5–O bond
via enamide intermediates. In the second approach, the starting α-oxoketene
dithioacetals or β-(methylthio)-β-(het)Âarylenones were
subjected to base induced conjugate addition–elimination with
various primary amides to furnish β-aroylenamides, which, on
subsequent iodine catalyzed intramolecular oxidative C–H functionalization/C–O
bond formation, afforded the corresponding regioisomeric 2-(het)Âaryl/alkyl-4-(methylthio)/(het)Âaryl-5-(het)Âaroyloxazoles
in excellent yields. The methodology has also been extended for the
synthesis of regioisomeric 4- or 5-aminooxazoles and 4- or 5-(<i>n</i>-butyl)Âoxazoles from the corresponding 4- or 5-(methylthio)Âoxazoles
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
One-Pot Synthesis of 2‑(Het)aryl/alkyl-3-cyanobenzofurans from 2‑(2-Bromoaryl)-3-(het)aryl-3-(methylthio)acrylonitriles and Benzyl Carbamate
A one-pot synthesis of 2-(het)Âaryl/alkyl-3-cyanobenzofurans
has
been reported. The overall sequence involves base-induced reaction
of 2-(2-bromoaryl)-3-(het)Âaryl-3-(methylthio)Âacrylonitriles with benzyl
carbamate, generating α-(het)Âaroyl-α-(2-bromoaryl)Âacetonitriles,
which are in situ subjected to copper-catalyzed intramolecular <i>O</i>-arylation, furnishing the 2-(het)Âaryl/alkyl-3-cyanobenzofurans
in high yields. A probable mechanism for the base-induced cleavage
of 2-(2-bromoaryl)-3-(het)Âaryl-3-(methylthio)Âacrylonitriles to α-(het)Âaroyl-α-(2-bromoaryl)Âacetonitriles
in the presence of benzyl carbamate has been proposed
One-Pot Synthesis of 2‑(Het)aryl/alkyl-3-cyanobenzofurans from 2‑(2-Bromoaryl)-3-(het)aryl-3-(methylthio)acrylonitriles and Benzyl Carbamate
A one-pot synthesis of 2-(het)Âaryl/alkyl-3-cyanobenzofurans
has
been reported. The overall sequence involves base-induced reaction
of 2-(2-bromoaryl)-3-(het)Âaryl-3-(methylthio)Âacrylonitriles with benzyl
carbamate, generating α-(het)Âaroyl-α-(2-bromoaryl)Âacetonitriles,
which are in situ subjected to copper-catalyzed intramolecular <i>O</i>-arylation, furnishing the 2-(het)Âaryl/alkyl-3-cyanobenzofurans
in high yields. A probable mechanism for the base-induced cleavage
of 2-(2-bromoaryl)-3-(het)Âaryl-3-(methylthio)Âacrylonitriles to α-(het)Âaroyl-α-(2-bromoaryl)Âacetonitriles
in the presence of benzyl carbamate has been proposed
Additional file 2: of Steroids in fluid and/or vasoactive infusion dependent pediatric shock: study protocol for a randomized controlled trial
Summary of mechanistic studies. This table summarizes the mechanistic studies that will be performed as part of the STRIPES pilot study, including the rationale, timing, and amount of blood sample required for each test. (PDF 202 kb