ABSTRACT
The reaction of 1,1-bis(triflyl)ethylene generated in situ with enolizable carbonyls yielded δ-oxo-1,1-bis(triflyl)alkane derivatives. Their acidities in both the gas and solution phases were determined.
Subject(s)
Alkanes/chemical synthesis , Combinatorial Chemistry TechniquesABSTRACT
(Z)-Selective olefination of several lactones with ketene silyl acetals was achieved by the catalysis of carbon acids (C-H acids) having a bis(triflyl)methyl group as an acidic functionality; in particular, the triple carbon acid having three bis(triflyl)methyl groups in phloroglucinol shows an excellent catalytic performance.
Subject(s)
Alkenes/chemistry , Carbonic Acid/chemistry , Lactones/chemistry , Acetals/chemistry , Catalysis , Ethylenes/chemistry , Ketones/chemistry , StereoisomerismSubject(s)
Acids/chemistry , Mesylates/chemistry , Alkylation , Catalysis , Crystallography, X-Ray , Esterification , Molecular StructureABSTRACT
In the absence of any additional catalysts, the reactions of (CF(3)SO)(2)CH(2), aldehydes, and 1,3-dienes gave gem-bis(triflyl)cyclohexenes in excellent yields with high regioselectivity. gem-Bis(triflyl)cyclohexene products can be easily converted to the corresponding aryl trifluoromethyl sulfones.
Subject(s)
Sulfones/chemistry , Sulfones/chemical synthesis , Aldehydes/chemistry , Alkenes/chemistry , Cyclohexenes/chemistry , Fluorine/chemistry , Stereoisomerism , Substrate SpecificityABSTRACT
In situ-generated silyl methide species (R(3)Si-CTf(2)R') effectively catalyzed the reaction of ß-substituted α,ß-unsaturated aldehydes with silicon dienoates such as 3-bromo-2-TESO-furan to give the corresponding γ-adducts with excellent 1,4-selectivity and good anti selectivity.
Subject(s)
Aldehydes/chemistry , Organosilicon Compounds/chemistry , Organosilicon Compounds/chemical synthesis , Catalysis , Molecular Structure , StereoisomerismABSTRACT
1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane (Tf(2)CHCH(2)CHTf(2)) is one of the most effective Brønsted acid precatalysts for the Mukaiyama aldol type reactions of sterically hindered ketones. By using Tf(2)CHCH(2)CHTf(2) in a range from 0.5 to 2.0 mol %, the vinylogous Mukaiyama aldol reaction of alpha-substituted cyclohexanones with 2-silyloxyfurans smoothly proceeded to give the aldol products in excellent yield without the loss of diastereoselectivity. Under similar conditions, acyclic ketene silyl acetals also performed as nice nucleophiles toward sterically hindered ketones. These findings suggest that Tf(2)CHCH(2)CHTf(2) induced Mukaiyama aldol type reactions can overcome the steric hindrance between reaction sites.
Subject(s)
Acids/chemistry , Aldehydes/chemistry , Carbon/chemistry , Ketones/chemistry , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Electrospray IonizationABSTRACT
Silyl methide species in situ generated from 1,1,3,3-tetrakis(trifluoromethanesulfonyl)propane (Tf(2)CHCH(2)CHTf(2)) performed as an excellent acid catalyst for the vinylogous Mukaiyama-Michael reaction of alpha,beta-unsaturated ketones with 2-silyloxyfurans. Notably, the required loading of Tf(2)CHCH(2)CHTf(2) to obtain the 1,4-adducts in reasonable yield was significantly low (from 0.05 to 1.0 mol %). This carbon acid-mediated VMM reaction provides a powerful synthetic methodology to construct highly substituted gamma-butenolide structure.
Subject(s)
Furans/chemistry , Hydrocarbons, Fluorinated/chemistry , Organosilicon Compounds/chemistry , Propane/analogs & derivatives , Catalysis , Ketones/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , Propane/chemistry , StereoisomerismABSTRACT
The intramolecular Diels-Alder reaction of an ester-tethered 1,3,9-decatriene system was significantly accelerated in ionic liquids such as [emim]BF(4), [bmim]BF(4) and [bdmim]BF(4). Under the present conditions, the IMDA reaction proceeded smoothly without the use of Lewis acid catalysts to give cis-fused bicyclic lactones in good yield with high diastereoselectivity.
Subject(s)
Ionic Liquids/chemistry , Alkenes/chemistry , Esters/chemistry , Kinetics , Lactones/chemistry , Metals/chemistry , Organometallic Compounds/chemistry , Stereoisomerism , Substrate SpecificityABSTRACT
In(OTf)(3) was found to be a useful Lewis acid catalyst for direct alkylative Passerini reaction of aldehydes, isocyanides, and free aliphatic alcohols. In the present reaction, aromatic and alpha,beta-unsaturated aldehydes performed as nice substrates to give the corresponding alpha-alkoxy amide products in good yield.
Subject(s)
Alcohols/chemistry , Aldehydes/chemistry , Cyanides/chemistry , Mesylates/chemistry , Alkylation , CatalysisABSTRACT
The reaction of trifluoroacetaldehyde N,O-acetal derivatives with 2 molar equivalents of alkyllithium reagents proceeded viabeta-elimination of fluoride followed by alkyl transfer from excess alkyllithium to the generated ketene N,O-acetal intermediate at the beta-carbon of fluorine groups.
Subject(s)
Acetaldehyde/analogs & derivatives , Acetals/chemical synthesis , Fluorides/chemistry , Acetaldehyde/chemical synthesis , Acetaldehyde/chemistry , Acetals/chemistry , Alkylation , Ethylenes/chemistry , Ketones/chemistry , Nitrogen/chemistry , Oxygen/chemistryABSTRACT
A chemical library of 1,2,3-triazole fused carbohydrate mimetics was constructed. To synthesize enantiomerically pure mimetics, we developed a stereo- or diastereodivergent synthetic route from D-glucose, D-mannose and D-galactose as chiral sources. In this synthesis, an In(OTf)(3)-catalyzed tandem azidation-1,3-dipolar cycloaddition reaction of 1,1-dimethoxyhex-5-yne derivatives with TMSN(3) was used as the key step to construct the 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyridine framework. Additionally, NMR was used to carry out a conformational analysis of the synthesized mimetics, which are of structural interest since they have an N,O-acetal moiety in place of the anomeric position of normal pyranosides.
Subject(s)
Biomimetics , Carbohydrates/chemical synthesis , Triazoles/chemical synthesis , Alkynes/chemistry , Carbohydrates/chemistry , Cyclization , Molecular Conformation , Molecular Structure , Small Molecule Libraries , Stereoisomerism , Triazoles/chemistryABSTRACT
1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane was found as an excellent Brønsted acid catalyst for the Mukaiyama-Michael reaction of alpha,beta-enones with 2-silyloxyfurans; using beta,beta-disubstituted enones as a Michael acceptor, an excellent yield construction of quaternary carbon centers could be achieved; in addition, very low catalyst loading of Brønsted acid was used in a range from 0.05 to 1.0 mol%.
Subject(s)
Alkenes/chemistry , Furans/chemistry , Ketones/chemistry , Mesylates/chemistry , Propane/analogs & derivatives , Vinyl Compounds/chemical synthesis , Catalysis , Furans/chemical synthesis , Ketones/chemical synthesis , Propane/chemistry , Vinyl Compounds/chemistryABSTRACT
In this paper, we describe the synthesis of (+)-(1R( *),2R( *))-2-[(1S( *))-1-amino-1-carboxy-2-(9H-xanthen-9-yl)-ethyl]-1-fluorocyclopropanecarboxylic acid (+)-16a, a compound, that is, fluorinated at the alpha position of the carboxylic acid in the cyclopropane ring of a group II mGluRs antagonist, 1 (LY341495), using a previously reported stereoselective cyclopropanation reaction. The fluorinated compound (+)-16a exhibited almost the same affinity (IC(50)=3.49 nM) for mGluR2 as 1 but had a superior pharmacokinetic profile. Furthermore, a marked elevation of the plasma levels of (+)-16a was observed following the administration of a prodrug, (+)-17.
Subject(s)
Receptors, Metabotropic Glutamate/antagonists & inhibitors , Xanthenes/chemical synthesis , Xanthenes/pharmacology , Animals , Crystallography, X-Ray , Liver/drug effects , Liver/metabolism , Male , Models, Molecular , Molecular Structure , Prodrugs/chemical synthesis , Prodrugs/chemistry , Prodrugs/pharmacology , Protein Binding , Rats , Receptors, Metabotropic Glutamate/metabolism , Structure-Activity Relationship , Xanthenes/chemistryABSTRACT
We have developed novel bidentate Lewis acids that efficiently promote the intramolecular cycloaddition reactions of ester-tethered substrates. Bis-aluminated triflic amide derivatives [TfN(AlR(1)R(2))2], which are generated by simply mixing triflic amide and 2 equiv of methyl aluminum or aluminum hydride, catalyzed intramolecular Diels-Alder (DA) reactions of ester-tethered 1,7,9-trienes and intermolecular DA reactions of alpha,beta-unsaturated lactones. We also found that bimetallic Lewis acid derived from 1,1'-biphenyl-2,2'-di(triflyl)amide and dimethylaluminum chloride promoted the intramolecular [3 + 2] cycloaddition reaction of acrylate derivatives having an allylsilane part.
Subject(s)
Ethers/chemistry , Organometallic Compounds/chemistry , Aluminum , Catalysis , Cyclization , Fluorine Compounds/chemistry , Indicators and Reagents , Lactones/chemical synthesis , Silanes/chemistryABSTRACT
We successfully synthesized the potent and selective group II mGluR agonist (+)-1 (MGS0008) via a process incorporating the key step of efficient fluorination of epoxide (+/-)-5c. This method would be adaptable to large-scale synthesis to produce (+)-1 in multi-gram quantities.
Subject(s)
Cyclohexanes/chemical synthesis , Cyclohexanes/pharmacology , Excitatory Amino Acid Agonists/pharmacology , Receptors, Metabotropic Glutamate/agonists , Bridged Bicyclo Compounds , Dicarboxylic Acids , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Electrospray IonizationABSTRACT
In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)(2) catalyst, N-arylation (aromatic amination) of various o-tert-butylanilides with p-iodonitrobenzene proceeds with high enantioselectivity (88-96% ee) to give atropisomeric N-(p-nitrophenyl)anilides having an N-C chiral axis in good yields. Atropisomeric anilide products highly prefer to exist as the E-rotamer which has trans-disposed o-tert-butylphenyl group and carbonyl oxygen. The application of the present catalytic enantioselective N-arylation to an intramolecular version gives atropisomeric lactam derivatives with high optical purity (92-98% ee). The reaction of the lithium enolate prepared from the atropisomeric anilide and lactam products with various alkyl halides gives alpha-alkylated products with high diastereoselectivity (diastereomer ratio = 13:1 to 46:1).
Subject(s)
Anilides/chemical synthesis , Nitrobenzenes/chemistry , Amination , Anilides/chemistry , Catalysis , Crystallography, X-Ray , Molecular Conformation , Palladium/chemistry , StereoisomerismABSTRACT
In the presence of the Trost ligands-Pd catalysts, N-monoallylation of bis(2,4,6-triisopropylbenzne)sulfonylamides derived from meso-1,2-diamines proceeds with good to excellent enantioselectivity (85-96% ee) to give asymmetric desymmetrization products. Under the same conditions, in the reaction with meso-bistolunesulfonylamide derivatives, reversal of the enantioselectivity is observed.
Subject(s)
Allyl Compounds/chemistry , Diamide/chemical synthesis , Organometallic Compounds/chemistry , Palladium/chemistry , Alkylation , Catalysis , Diamide/analogs & derivatives , Diamide/chemistry , Molecular Structure , StereoisomerismABSTRACT
Reactions of o-(alkoxymethyl)styrene derivatives with a stoichiometric amount of zirconocene-butene complex (zirconocene equivalent, "Cp(2)Zr") brought about an insertion of the zirconocene species into a benzylic carbon-oxygen bond. The oxidative insertion of Cp(2)Zr to the benzylic carbon-oxygen bond is a result of sequential reactions: (i) formation of zirconacyclopropane by the ligand exchange with o-(alkoxymethyl)styrene, (ii) elimination of the alkoxy group through an aromatic conjugate system giving metalated o-quinodimethane species, and (iii) transfer of zirconium metal to the benzylic position. Through use of a catalytic amount of "Cp(2)Zr", however, unprecedented homo-coupling reactions (dimerization) of o-(alkoxymethyl)styrene derivatives occurred to give a tetracyclic compound. On the other hand, reactions of o-(1-alkoxyisopropyl)styrene derivatives gave rise to the analogous tetracyclic compounds regardless of the amount of "Cp(2)Zr" (stoichiometric or catalytic). Heterocoupling product between o-(1-alkoxyisopropyl)styrene and styrene congeners was obtained in high cis stereo- and regioselectivity by treating o-(1-alkoxyisopropyl)styrene derivatives with "Cp(2)Zr" in the presence of an excess amount of styrene derivatives.
ABSTRACT
In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, N-arylation of ortho-tert-butyl-NH-anilides with 4-nitroiodobenzene proceeds with high enantioselectivity (89-95% ee) to give optically active atropisomeric anilides possessing N-C chiral axis. Furthermore, the intramolecular version of the present catalytic asymmetric N-arylation gave atropisomeric lactams with high optical purity (94-96% ee).