A new polymer-supported reagent for the synthesis of beta-lactams in solution

A modified Mukaiyama reagent was prepared on a PS-DVB resin. This reagent was used for the preparation of beta-lactams, using the Staudinger reaction. The products were obtained by generating the ketene from a carboxylic acid under sonication with the resin followed by reaction with the imine. Excess of the imine was removed by reduction followed by acid scavenging.     

Synthesis of naphthalenes through three-component coupling of alkynes, Fischer carbene complexes, and benzaldehyde hydrazones via isoindole intermediates

The synthesis of naphthalene derivatives through three-component coupling of 2-alkynylbenzaldehyde hydrazones with carbene complexes and electron-deficient alkynes has been examined. The reaction involves formation of an isoindole derivative, followed by intramolecular Diels-Alder reaction, followed by nitrene extrusion. The reaction was highly regioselective using unsymmetrical alkynes.     

One-pot three-component tandem metathesis/Diels-Alder reaction

[reaction: see text] A tandem enyne, diene-ene metathesis reaction followed by Diels-Alder reaction accomplished a stereoselective three-component reaction protocol with four stereocenters.     

Synthesis of polyhydroxylated bicyclic tetrahydrofurans and tetrahydropyrans via a stereoselective domino cyclization/reduction reaction

A novel reaction cascade involving a Lewis acid-induced migration of an isopropylidene protecting group followed by the formation of a pyranose or furanose ring and subsequent reduction of the hemiacetal is described. Depending on the reaction conditions, as well as, the stereochemistry of the substrate, polyhydroxylated tetrahydrofurans or tetrahydropyrans can be obtained in reasonable yields. The synthons used in this transformation were prepared via a highly stereoselective one-pot tandem reaction, consisting of a 1,4-Michael addition of vinylmagnesium bromide to d-glucose-derived cyclohexenone followed by aldol reaction with 2,3-O-isopropylidene-d-glyceraldehyde.     

Intramolecular Diels-Alder Reaction of Furans with Allenyl Ethers Followed by Phenylthio and Trialkylsilyl Groups Rearrangement

A new reaction involving an intramolecular Diels-Alder reaction of a furan diene with an allenyl ether dienophile followed by phenylthio group rearrangement was discovered. Treatment of the propargyl ethers 2a-c with t-BuOK in t-BuOH at 85 ° C gave the phenylthio group rearrangement products 5a-c and 6a-c . A reaction involving an intramolecular Diels-Alder reaction of a furan diene with an allenyl ether dienophile followed by trialkylsilyl group rearrangement is also demonstrated.     

Synthesis of 3,4-Dihydro-2-methyl-3-oxo-N-aryl-2H-[1]benzothieno[3,2-e1,2-thiazine-4-carboxamide 1,1-Dioxides

A novel synthesis of the title compounds, representing a new heterocyclic ring system, is described. Chlorosulphonation of 3-methylbenzo[b]thiophene followed by reaction with methylamine gave sulfonamide, 4 . Lithiation of 4 , followed by quenching with carbon dioxide yielded acetic acid, 5 . Cyclodehydration of 5 to benzothienothiazine 6 followed by reaction with aryl isocyanates afforded the desired benzothieno[3,2-e]-1,2-thiazine-4-carboxamides 1a-f.     

Total synthesis of (+/-)-stemodinone via an efficient ring-exchange strategy

A total synthesis of (+/-)-stemodinone, a tetracyclic stemodane diterpene, from the known tricyclic methyl olefin 11 is described. The key steps involve an efficient ring-exchange reaction and palladium(0)-catalyzed lactone migration. The ring-exchange strategy for controlling the stereochemistry was based on an initial Diels-Alder reaction to form a new ring followed by cleavage of the original ring. Cleavage of the original ring of the Diels-Alder adduct 9 was achieved by an initial regio- and chemoselective Baeyer-Villiger oxidation followed by the Pd(0)-catalyzed lactone-migration reaction reported by us.     

Insights into the Oxidation Chemistry of 2‐Hydroxypurine by Electrochemical Methods

The oxidation chemistry of 2‐hydroxypurine has been investigated in phosphate containing supporting electrolytes at pH 1.4–9.8 at a pyrolytic graphite electrode by voltammetric studies, spectral studies, controlled potential electrolysis and related techniques. The kinetics of decay of the UV‐absorbing intermediate generated during electrooxidation was followed spectrophotometrically and the decay occurred in a pseudo‐first‐order reaction. The course of the electrode reaction has been deduced to involve a 6e, 6H⁺ oxidation of 2‐hydroxypurine via the formation of 2, 8‐dihydroxypurine. The electrooxidation of 2‐hydroxypurine has been found to be an EC reaction (electrode reaction followed by chemical reactions) in which charge transfer is followed by competitive chemical reactions. A detailed interpretation of the redox mechanism of 2‐hydroxypurine has been presented.     

Stereospecific synthesis of novel methyl-substituted mono- and di-methoxy conduritols

Methyl-monomethoxy conduritol-B and methyl-dimethoxy conduritol-B were synthesized starting from 2-methylbenzo-1,4-quinone. Bromination of 2-methylbenzo-1,4-quinone was followed by the reduction of the carbonyl groups with NaBH₄ to give a dioldibromo compound. Methyl-dimethoxy conduritol-B was synthesized from the reaction of the dioldibromo compound with CH₃ONa, followed by acetylation with Ac₂O-pyridine to obtain methyl-dimethoxy diacetate. On the other hand, acetylation of the methyl-dioldibromo compound followed by reaction with LiOH gave a monoepoxide compound stereoselectively. The reaction of the epoxide with H⁺/Ac₂O afforded the monobromo triacetate. Controlled reaction of monobromo-triacetate with CH₃ONa in MeOH furnished the desired new methyl-monomethoxy conduritol-B. The structures of all synthesized compounds were characterized by spectroscopic methods.     

Stereodivergent synthesis of 1,4-bifunctional compounds by regio- and diastereoselective Pd-catalyzed allylic substitution reaction

Highly stereoselective synthesis of 1,4-bifunctional compounds was accomplished via 1,2-asymmetric induction to α-oxyaldehyde and α-oxyketone followed by regio- and diastereoselective Pd-catalyzed allylic substitution reaction. We found that trifluoroacetate is a suitable leaving group for the allylic substitution reaction. Various nucleophiles containing carbon, nitrogen, and sulfur can be applied to the method. Both 1,4-syn- and 1,4-anti-adducts were synthesized with high stereoselectivity by using stereodivergent reduction of the propargyl alcohols followed by allylic substitution reaction.     

Synthesis of highly functionalized indeno[1,2-b]furans

Some novel functionalized indeno[1,2-b]furans were synthesized from the reaction of indandione/indanone and aldehydes at room temperature followed by the reaction of the Knoevenagel condendensed intermediate with 4-hydroxycoumarins in the presence of iodine as catalyst in dimethyl sulfoxide (DMSO) under thermal conditions. The reaction involved in a condensation and Michael addition followed by lactone ring opening and intramolecular cyclization process to afford the product in high yield in easy work-up procedure.     

Immobilized alpha-diazophosphonoacetate as a versatile key precursor for palladium catalyzed indole synthesis on a polymer support

Rh(II)-catalyzed N-H insertion reaction of immobilized alpha-diazophosphonoacetate with 2-haloanilines followed by Horner-Emmons reaction gave immobilized enaminoesters, which were efficiently cyclized to indoles via intramolecular palladium catalyzed reaction on a polymer support.     

Direct synthesis of beta-aminoketones from amides via novel sequential nucleophilic substitution/Michael reaction

[reaction: see text] The synthesis of beta-aminoketones from amides can be achieved in a process consisting of sequential nucleophilic substitution at the carbonyl group by vinylmagnesium bromide followed by Michael reaction after quench of the first reaction by water.     

On the Diels-Alder reactions of pentadienyl maleates and citraconates

Reactions between conjugated dienols and maleic anhydride provide either cis-fused or trans-fused bicyclic products as major products, depending upon how the reaction is carried out. Simply mixing the two reactants together generally leads to cis-fused lactone acids in thermal reactions which proceed viaintermolecular Diels-Alder reaction followed by intramolecular esterification. Pre-forming the maleate half ester derivative followed by heating affords predominantly trans-fused lactone acids in good yields by way of an intramolecular Diels-Alder (IMDA) reaction. Sorbyl citraconate half esters undergo a rapid thermolytic fragmentation in refluxing toluene to form the dienol and citraconic anhydride. The resulting diene-dienophile pair undergo an intermolecular cycloaddition followed by a rapid intramolecular esterification to give cis-fused bicyclic lactone acids as major products. The IMDA reaction of citraconic half esters is sufficiently rapid in DMSO to dominate over fragmentation: the exo-cycloadduct is formed almost exclusively. Nine literature reports of endo-selective IMDA reactions of triene acids are erroneous; the cycloadditions proceed in an intermolecular manner.     

Asymmetric synthesis of enantioenriched (+)-elaeokanine A

The key transformation in the total synthesis of (+)-elaeokanine A was accomplished by asymmetric deprotonation of N-Boc pyrrolidine, followed by the reaction of the in situ generated enantioenriched stereogenic cuprate reagent with (E)-4-bromo-1-iodo-1-trimethylsilyl-1-butene with retention of configuration. N-Boc deprotection, followed by a one-pot olefin isomerization and intramolecular amine alkylation afforded a bicyclic vinyl bromide that was converted into (+)-elaeokanine A by sequential halogen metal exchange and reaction of the organolithium reagent with N-butanoylmorpholine.     

Synthesis of triazoles from nonactivated terminal alkynes via the three-component coupling reaction using a Pd(0)-Cu(I) bimetallic catalyst

The synthesis of triazoles via the three-component coupling reaction of unactivated terminal alkynes, allyl carbonate, and trimethylsiyl azide under the Pd(0)-Cu(I) bimetallic catalyst is developed. The reaction most probably proceeds through the formation of a pi-allylpalladium azide complex and a copper-acetylide followed by a successive [3 + 2] cycloaddition. The deallylation of the resulting allyltriazoles proceeds very easily by the Ru-catalyzed isomerization followed by the ozonolysis of the resulting propenyltriazoles to give the triazoles in high yields.     

Multicomponent synthesis of dihydrobenzoxazepinones by coupling Ugi and Mitsunobu reactions

Various dihydrobenzo[f][1,4]oxazepin-5-ones have been convergently prepared in 2-3 steps by coupling Ugi and Mitsunobu reactions. Two alternative methodologies were used: in the first one the Ugi condensation was followed by a Mitsunobu cyclization (2 steps); in the second one an intermolecular Mitsunobu reaction was followed by a deprotection step and then by an intramolecular Ugi reaction. Also a "convertible" isocyanide was used.     

Investigation of the rh-catalyzed asymmetric reductive aldol reaction. Expanded scope based on reaction analysis

[reaction: see text] A series of experiments are described that suggest that the Rh-catalyzed reductive aldol reaction proceeds by addition of a Rh(I) hydride, generated in situ, to the reacting acrylate followed by a stereochemistry-controlling aldol addition reaction. On the basis of this hypothesis, reaction conditions are engineered that allow for increased substrate scope.     

A facile method for the synthesis of nicotinonitriles from ketones via a one-pot chloromethyleneiminium salt mediated three-component reaction

Simple enolizable ketones such as acetophenones and benzalacetones were treated with malononitrile under Vilsmeier-Haack reaction conditions to afford 2-chloronicotinonitriles. The reaction proceeds via a one-pot chloromethyleneiminium salt mediated three-component reaction followed by sequential cyclization and aromatization under Vilsmeier-Haack reaction conditions.     

Ugi multicomponent reaction followed by an intramolecular nucleophilic substitution: convergent multicomponent synthesis of 1-sulfonyl 1,4-diazepan-5-ones and of their benzo-fused derivatives

A short, two-step approach to the synthesis of diazepane or diazocane systems, based on a Ugi multicomponent reaction followed by a subsequent intramolecular SN2 reaction was studied. 1-sulfonyl tetrahydrobenzo[e]-1,4-diazepin-1-ones 1 were obtained in very high yield through a Ugi multicomponent reaction followed by Mitsunobu cyclization. On the other hand, aliphatic 1-sulfonyl 1,4-diazepan-5-ones 2 could be obtained employing different cyclization conditions (sulfuryl diimidazole). A similar approach toward diazocane rings using hydroxamates as nucleophiles was less successful, affording only O-cyclized adducts or unexpected side products. A mechanistic explanation of the observed outcomes is proposed.