RESUMEN
In this study, we discover a good NO/HNO precursor, N-hydroxypyridinesulfonamide, and the regioselective radical nitrososulfonylation reaction of propargyl alcohols. Direct and unique isoxazole synthesis afforded a good-to-high yield of 5-alkyl-3-aryl-4-pyridinesulfonylisoxazoles. Copper-catalyzed aerobic oxidation could efficiently proceed in the presence of thiazolidine-2,4-dione. This work provides a powerful method for the synthesis and functionalization of alkyl-substituted isoxazoles and explores a new investigation route for drug-drug discovery.
RESUMEN
Dehydration is an abundant and promising process in chemical, biochemical, and industrial fields. Dehydration methods can contribute to building a modern and sustainable society with minimal environmental impact. Breakthrough advances in the dehydrative SN1 reaction can be achieved through the discovery of new cationic indium catalysts. Here we show that the breakthrough advances in the dehydrative SN1 reaction can be achieved using the cationic indium catalysts. The dehydrative carbon-carbon bond formation of α-alkyl propargyl alcohols afforded a wide variety of α-aryl- and heteroaryl-propargyl compounds. Mechanistic investigations into this process revealed that the InCl3/AgClO4/Bu4NPF6/1,1'-binaphthol catalytic system generated a powerful cationic indium catalyst that could promote the dehydration of alcohols. Labile α-alkyl propargyl cations were found to self-condense, and the catalyst system efficiently regenerated propargyl cations for reaction with nucleophiles. This propargylation reaction directly proceeded from the corresponding alcohols under mild and open-air conditions and tolerated a broad scope of functional groups. Furthermore, a wide variety of nucleophiles, including aromatic and heteroaromatic compounds, phenols, alcohols, and sulfonamides, reacted with the corresponding cations to afford the propargyl compounds in good to high yields. Finally, the synthetic utility of this reaction was demonstrated by the synthesis of colchicine and allocolchicine analogues. The dehydration process could help create new compounds that were previously impossible to synthesize and is more eco-friendly and efficient than conventional methods.
RESUMEN
A unique 1,7-S- and Se-shift reaction under Pummerer reaction conditions of 4-alkenyl-3-sulfinyl- and seleninylpyrroles was described. The usual Pummerer reaction of 4-(alkenylaminomethyl)-3-phenylsulfinylpyrroles and a successive reaction with tetrabutylammonium hydroxide (TBAH) yielded either pyrrolo[3,2-c]azepines or N-pyrrol-3-ylmethyl-N-(4-hydroxy-3-sulfanylpropyl)-p-toluenesulfonamides (diols). Seleno-Pummerer reactions of 3-selanylmethylpyrroles also proceeded via in situ generation of selenoxides, followed by a treatment with TBAH.
RESUMEN
In this study, the first aza-Henry reaction of nitriles with nitromethane in a CuI/Cs2CO3/DBU system is described. The process was conveniently and directly used for the synthesis of ß-aminonitroalkenes 2a-x and tolerated aryl-, alkyl-, hetaryl-, alkenyl-, and alkynylnitriles. The resulting aminonitroalkenes 2 could be successfully transformed to the corresponding 2-nitroacetophenones, 2-amino-1-halonitroalkenes, 2-alkylaminonitroalkenes, or 3-nitropyridines. In the presence of H2O, the aza-Henry reaction turned the reaction path to the nitrile hydration to exclusively yield the amides 3a-s.
RESUMEN
The Ni-Pd catalyzed addition-cyclization of sulfanyl 1,6-diynes 2-9 with nucleobases is described. The reactions of N-tethered 1,6-diynes with N3-benzoylthymine, N4,N4-bis(Boc)cytosine, N3-benzoyluracil and N6,N6-bis(Boc)adenine exclusively afforded the pyrrolylmethyl and furylmethyl nucleotides in good yields. Deprotection of nucleobases was completed by treatment with acids or bases. Furthermore, the reactions of pyrroles and furans with nucleophiles such as alkoxides and amines underwent detosylation and conversion to the alkoxymethyl- and arylaminomethyl-pyrroles and furans in good yields.
RESUMEN
A protocol for the direct synthesis of azepines using a hafnium(III)-catalyzed [6 + 1] annulation of N-tethered ynenitriles with Reformatsky reagents is reported. A broad range of 3-amino-2,7-dihydro-1H-azepine-4-carboxylates 4aa-4he were obtained in high yields and with excellent functional group tolerance. The copper-mediated reactions of isolable Blaise intermediates (enamino esters 3), uniquely underwent 5-endo cyclization to afford the ß-2,5-dihydropyrrolyl α,ß-unsaturated esters 5aa-5fc, which exhibit anticancer activity.
RESUMEN
Pyrazoles direct: propargyl alcohols undergo hydrazination when treated with p-tosyl hydrazide in the presence of catalytic amounts of either Sc(OTf)(3) or La(OTf)(3) (see scheme; Tf=trifluoromethanesulfonyl). Propargyl hydrazides are converted into either N-tosyl or N-H pyrazoles when treated with an acid or a base, respectively. The one-step acid-catalyzed hydrazination/cyclization of propargyl alcohols directly affords pyrazoles in high yields.
Asunto(s)
Alquinos/síntesis química , Hidrazinas/síntesis química , Propanoles/síntesis química , Pirazoles/síntesis química , Alquinos/química , Aminación , Catálisis , Hidrazinas/química , Estructura Molecular , Propanoles/química , Pirazoles/química , EstereoisomerismoRESUMEN
Copper(I)-catalyzed alkynylation-cyclization of 4-oxahepta-1,6-diynes 1 with a wide variety of terminal alkynes proceeded to give (3E,4Z)-3-(phenylsulfanylmethylene)-4-(2-propynylidene)tetrahydrofuran-2-yl]benzenes 2aa-he in high yields with complete regio- and stereoselectivity.
Asunto(s)
Cobre/química , Compuestos de Azufre/química , Alquilación , Catálisis , Ciclización , Modelos Moleculares , Estructura Molecular , EstereoisomerismoRESUMEN
Direct scandium- and lanthanum-catalyzed etherifications of propargyl alcohols 1 and 6 in MeNO2-H2O provided propargyl ethers 3, 4 and 7 in high yields. In addition, reactions of 1 and 6 with thiols exclusively yielded the corresponding propargyl sulfides.
Asunto(s)
Alquinos/química , Éteres/química , Ácidos de Lewis/química , Metales/química , Nitritos/química , Propanoles/química , Sulfuros/química , Agua/química , Alquinos/síntesis química , Catálisis , Éteres/síntesis química , Lantano/química , Escandio/química , Compuestos de Sulfhidrilo/química , Sulfuros/síntesis químicaRESUMEN
Propargylations of 1,3-diketones using 3-sulfanyl and 3-selanylpropargyl alcohols 1 in MeNO(2)-H(2)O gave alkynyl ketones 2a-m, 2o-v and 6,7-dihydro-5H-cyclohexa[b]pyran-5-ones 3k-n. With some bases, the useful propargylated 1,3-diketones underwent intramolecular cyclization to give 6,7-dihydro-5H-benzofuran-4-ones 4a-i or 4,5,6,7-tetrahydrobenzofurans 5p, 6p-v.
Asunto(s)
Alquinos/química , Furanos/química , Cetonas/química , Propanoles/química , Piranos/química , Escandio/química , Catálisis , Ciclización , Compuestos de Selenio/química , Compuestos de Azufre/químicaRESUMEN
New cyclizations of 1-sulfanyl- and -selanyl-4-oxa-1,6-heptadiynes using sodium alkoxide or thiolates provided 4-alkoxymethyl-3-phenylsulfanyl- and 3,4-bis(sulfanylmethyl)furans in high yields.
Asunto(s)
Selenio/química , Azufre/química , Ciclización , Furanos/química , Isomerismo , Estructura Molecular , Fenómenos Químicos OrgánicosRESUMEN
Alpha-sulfanyl and alpha-selanyl propadienyl cations were easily generated by the catalytic system, scandium triflate-nitromethane-H(2)O in the presence of Bu(4)NHSO(4), to regioselectively afford the multifunctionalized thiazoles and selenazoles in high yields.
Asunto(s)
Compuestos de Organoselenio/química , Compuestos de Sulfhidrilo/química , Tiazoles/síntesis química , Tioamidas/química , Catálisis , Cationes , Ciclización , Mesilatos/química , Estructura Molecular , Compuestos de Organoselenio/síntesis química , Escandio/química , Estereoisomerismo , Tiazoles/químicaRESUMEN
The scandium-catalyzed substitution reactions of the phenylsulfanyl and phenylselanyl propargyl alcohols 3a- i and 7a- h regioselectively proceeded to give the propargylated compounds 4 and 8 in high yields.
RESUMEN
The scandium-catalyzed reactions of alpha-organosulfanyl and organoselanyl-alpha-fluoroacetates 1-2, acetamides 3-4 and acetonitrile 5 with soft nucleophiles proceeded to give the products 6a-b, 7a-c, 8a-c, 9a-e in good to high yields. We also successfully performed the scandium-catalyzed intramolecular cyclization reactions and obtained the unique 5-methylene-2-oxotetrahydropyrans 16-17.
Asunto(s)
Carbono/química , Fluoroacetatos/síntesis química , Escandio/química , Compuestos de Azufre/química , Catálisis , Ciclización , Fluoroacetatos/química , Estructura Molecular , EstereoisomerismoRESUMEN
Reactions of alpha-tellanyl-beta-ethoxyvinyl lithiums of aldehydes and ketones proceeded in good to high yields and the successive treatment with acids gave the alpha-tellanyl alpha,beta-unsaturated aldehydes. alpha-Tellanyl alpha,beta-unsaturated aldehydes easily transformed to more useful compounds.
Asunto(s)
Aldehídos/química , Cetonas/química , Litio/química , Compuestos Organometálicos/síntesis química , Telurio/química , Estructura Molecular , Compuestos Organometálicos/químicaRESUMEN
3,4-Dichalcogenopenta-2,4-dienylation of aldehydes proceeded in good to high yields using 4-ethoxy-1-(benzenesulfenyl)-2-(methanesulfenyl)- (5), 4-ethoxy-1,2-bis(benzenesulfenyl)but-1,3-diene (6), and 1-selenenyl derivatives 7 and 8. This novel four-carbon homologation could be applied to a synthesis of 3,4,7,8-tetrakis(benzenesulfenyl)-10,10-dimethylundeca-2,4,6,8-tetraenal (20).
Asunto(s)
Aldehídos/síntesis química , Litio/química , Compuestos de Selenio/síntesis químicaRESUMEN
5-(phenylselenenyl)- and 5-(phenylsulfenyl)-4-ethoxy-1-phenyl-2,4-pentadien-1-ones (2) and (3) underwent [4+2] cycloaddition with N-methyl and N-phenylmaleimides and successive isomerization to give the 7-benzoyl-3a,4,5,7a-tetrahydro-1H-isoindole-1,3(2H)-diones 5, 8 and 9 in good yields. The 4-ethoxy group on the 2,4-pentadien-1-one was found to be effective to facilitate the cycloaddition with dienophiles. We also performed other [4+2] cycloadditions of 2,4-pentadien-1-ones with DMAD or naphthoquinone.
Asunto(s)
Alcadienos/síntesis química , Calcógenos/síntesis química , Alcadienos/química , Alcadienos/farmacocinética , Calcógenos/química , Calcógenos/farmacocinética , Electrones , EstereoisomerismoRESUMEN
(Z)- and (E)-2-Ethoxyperfluoro-2-(phenylselenenyl)alk-2-enenitriles 2-4 prepared by our original method underwent transmetalation on treatment with n-BuLi or EtMgBr, and the successive reaction with aldehyde and ketones afforded the corresponding allylic alcohols 10a-f, 9a, and 11a,b in good to high yields. Hydrolysis of the alcohols gave alpha-cyano-alpha,beta-unsaturated perfluoroalkyl ketones 13a-c, 13e, 12a, and 15a. alpha-Cyanoperfluoroalkyl ketones were easily converted to alpha,beta-unsaturated 3-aryl-2-cyanoallylic alcohols 18-22 having interesting biological activities and chemical reactivities.
Asunto(s)
Aldehídos/síntesis química , Nitrilos , Acilación , Aldehídos/química , Indicadores y Reactivos , Conformación Molecular , Estructura MolecularRESUMEN
Highly useful C-C bond formation using 2-ethoxy-3-(phenylseleno)prop-2-enal acetal 2 was examined with various Lewis acids. The reaction of 2 with the silyl enol ether in the presence of BF(3)*Et2O, ZnBr2, or SnBr4 regioselectively provided (Z)-3,4-diethoxy-5-(phenylseleno)pent-4-enophenone 5a in high yields. On the other hand, the reaction with other Lewis acids such as EtAlCl2 or SnCl4 gave 5-(phenylseleno)- 6 or non-selenopentane-1,4-dione 7, respectively. Novel prop-2-enal acetals 2-4 and 13-15 reacted with various nucleophiles to give pent-4-enophenones 5a,b, 10a, 12, and 16-18, S-ethyl pent-4-enoate 5b, alkylated vinylic sulfide 10b, 3-pentenenitrile 5d, and 10c. A versatile pent-4-enophenone 5a could be converted to tetrahydrofuran 20 and penta-2,4-dienophenone 19, the Diels-Alder reactions of which with dienophiles gave the adducts 24 and 25.
RESUMEN
α-(Methylthio)- or α-(phenylthio)-substituted perfluoroacylolefinations of nonenolizable aldehydes using the ß-lithio-ß-thio-perfluoroalkyl enol ethers 1-4 stereoselectively proceeded to give (Z)-α,ß-unsaturated perfluoroalkyl ketones 9a-e, 10a-c, 11a-c, and 12a. The α-(thio)-α,ß-unsaturated trifluoromethyl ketones were easily converted to 3-(thio)-2-(trifluoromethyl)-1,3-butadienes 21a-c and 22a,b in moderate to high yields (41-85%).