Showing papers on "Intramolecular reaction published in 2008"

Intramolecular Pd(II)-catalyzed oxidative biaryl synthesis under air: reaction development and scope.

Abstract: New reaction conditions for intramolecular palladium(II)-catalyzed oxidative carbon-carbon bond formation under air are described. The use of pivalic acid as the reaction solvent, instead of acetic acid, results in greater reproducibility, higher yields, and broader scope. This includes the use of electron-rich diarylamines as illustrated in the synthesis of three naturally occurring carbazole products: Murrayafoline A, Mukonine, and Clausenine. A variety of side products have also been isolated, casting light on competing reaction pathways and revealing new reactivity with palladium(II) catalysis.

Palladium-catalyzed method for the synthesis of carbazoles via tandem C-H functionalization and C-N bond formation.

Abstract: The development of a new method for the assembly of unsymmetrical carbazoles is reported. The strategy involves the selective intramolecular functionalization of an arene C-H bond and the formation of a new arene C-N bond. The substitution pattern of the carbazole product can be controlled by the design of the biaryl amide substrate, and the method is compatible with a variety of functional groups. The utility of the new protocol was demonstrated by the concise synthesis of three natural products from commercially available materials.

Copper-Catalyzed Domino Annulation Approaches to the Synthesis of Benzoxazoles under Microwave-Accelerated and Conventional Thermal Conditions

Abstract: Two domino annulation approaches for benzoxazole synthesis have been developed. In the first approach, copper-catalyzed intermolecular cross-coupling of 1,2-dihaloarenes with primary amides initially forms the Ar−N bond of the benzoxazole ring, followed by copper-catalyzed intramolecular cyclization to form the Ar−O bond. Benzoxazoles were formed in good yields for the reaction of 1,2-dibromobenzene, but the reaction was not regioselective for the reaction of 3,4-dibromotoluene. Furthermore, the method is limited by the availability of 1,2-dihaloarenes. As a result of these limitations, an alternative more versatile one-pot domino annulation strategy was developed involving reaction of 2-bromoanilines with acyl chlorides in the presence of Cs2CO3, catalytic CuI, and the non-acylatable ligand 1,10-phenanthroline. Under these conditions initial acylation of the aniline is followed by copper-catalyzed intramolecular cyclization of the resultant 2-haloanilide to form the Ar−O bond of the benzoxazole ring. Opt...

InBr3-promoted divergent approach to polysubstituted indoles and quinolines from 2-ethynylanilines: switch from an intramolecular cyclization to an intermolecular dimerization by a type of terminal substituent group.

Abstract: Use of a 2-ethynylaniline having an alkyl or aryl group on the terminal alkyne selectively produced a variety of polyfunctionalized indole derivatives in moderate to excellent yields via indium-catalyzed intramolecular cyclization of the corresponding alkynylaniline. In contrast, employment of a substrate with a trimethylsilyl group or with no substituent group on the terminal triple bond, exclusively afforded polysubstituted quinoline derivatives in good yields via indium-promoted intermolecular dimerization of the ethynylaniline. This indium catalytic system successfully accommodated the intramolecular cyclization of other arylalkyne skeletons involving a carboxylic acid and an amide group.

N-tosyloxycarbamates as reagents in rhodium-catalyzed C-H amination reactions.

Abstract: Metal nitrenes for use in C-H insertion reactions were obtained from N-tosyloxycarbamates in the presence of an inorganic base and a rhodium(II) dimer complex catalyst. The C-H amination reaction proceeds smoothly, and the potassium tosylate that forms as a byproduct is easily removed by filtration or an aqueous workup. This new methodology allows the amination of ethereal, benzylic, tertiary, secondary, and even primary C-H bonds. The intramolecular reaction provides an interesting route to various substituted oxazolidinones, whereas the intermolecular reaction gives trichloroethoxycarbonyl-protected amines that can be isolated with moderate to excellent yields and that cleave easily to produce the corresponding free amine. The development, scope, and limitations of the reactions are discussed herein. Isotopic effects and the electronic nature of the transition state are used to discuss the mechanism of the reaction.

Stereodivergent methodology for the synthesis of complex pyrrolidines.

Abstract: The intramolecular reaction of oxime ethers and cyclopropane diesters results in the diastereoselective formation of substituted pyrrolo-isoxazolidines which serve as precursors to the ubiquitous pyrrolidine motif. A simple reversal of addition order of catalyst and substrate results in formation of two discrete diastereomers in a highly selective and predictable manner. The adducts are prepared in excellent yields from either enantiomer of an alkoxyamino-tethered cyclopropanediester, allowing efficient access to highly substituted homochiral pyrrolidines.

Copper-Catalyzed Synthesis of Benzimidazoles via Cascade Reactions of o-Haloacetanilide Derivatives with Amidine Hydrochlorides

Abstract: We have developed an efficient method for the synthesis of benzimidazoles via cascade reactions of o-haloacetoanilide derivatives with amidine hydrochlorides. The protocol uses 10 mol % CuBr as the catalyst, Cs2CO3 as the base, and DMSO as the solvent, and no ligand is required. The procedure proceeds via the sequential coupling of o-haloacetoanilide derivatives with amidines, hydrolysis of the intermediates (amides), and intramolecular cyclization with the loss of NH3 to give 2-substituted 1H-benzimidazoles.

Scope of the asymmetric intramolecular stetter reaction catalyzed by chiral nucleophilic triazolinylidene carbenes.

Abstract: A highly enantioselective intramolecular Stetter reaction of aromatic and aliphatic aldehydes tethered to different Michael acceptors has been developed. Two triazolium scaffolds have been identified that catalyze the intramolecular Stetter reaction with good reactivity and enantioselectivity. The substrate scope has been examined and found to be broad; both electron-rich and -poor aromatic aldehydes undergo cyclization in high yield and enantioselectivity. The tether can include oxygen, sulfur, nitrogen, and carbon linkers with no detrimental effects. In addition, the incorporation of various tethered Michael acceptors includes amides, esters, thioesters, ketones, aldehydes, and nitriles. The catalyst loading may be reduced to 3 mol % without significantly affecting the reactivity or selectivity of the reaction.

Enantioselective intramolecular hydroarylation of alkenes via directed C-H bond activation.

Abstract: Highly enantioselective catalytic intramolecular ortho-alkylation of aromatic imines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using [RhCl(coe)2]2 and chiral phosphoramidite ligands. Cyclization of substrates containing 1,1- and 1,2-disubstituted as well as trisubstituted alkenes were achieved with enantioselectivities >90% ee for each substrate class. Cyclization of substrates with Z-alkene isomers proceeded much more efficiently than substrates with E-alkene isomers. This further enabled the highly stereoselective intramolecular alkylation of certain substrates containing Z/E-alkene mixtures via a Rh-catalyzed alkene isomerization with preferential cyclization of the Z-isomer.

Gold(I)-catalyzed cycloisomerization of arylvinylcyclopropenes: an efficient synthetic protocol for the construction of indene skeletons.

Abstract: As the smallest of cycloolefins, the cyclopropenes are highly strained but readily accessible substances, which have been serving as useful building blocks in many organic reactions. It can bee seen that during the last several decades, thermal and photochemical skeleton rearrangements as well as metal-catalyzed/-mediated reactions of cyclopropene-containing compounds have attracted much attention from both synthetic and mechanistic viewpoints and numerous interesting transformations have been disclosed. For example, we recently have explored a new type of arylvinylcyclopropenes from the corresponding arylvinylidenecyclopropanes under basic conditions and have reported that the choice of Lewis acid catalyst can result in dramatic differences in the chemoselectivity of the rearrangement reactions of these vinylcyclopropenes, leading to naphthalene and indene derivatives (Scheme 1). This is because that different Lewis acids can form the key carbon cationic intermediates at the different positions of cyclopropane. In fact, trace of water in these systems plays a very important role to release H as the real catalyst if using BF3·OEt2 as the catalyst. Gold, which has emerged as the most efficient catalyst for the activation of alkynes, allenes and alkenes, has recently been a rising star of transition-metal catalysts. Since there is the similarity on the chemical behavior between LAu and H , we envisaged that intramolecular rearrangement may take place in an interesting manner in the presence of gold(I) under mild conditions. In this communication, we wish to report an efficient gold(I)-catalyzed intramolecular cycloisomerization of arylvinylcyclopropenes to produce indene derivatives in good to excellent yields. To the best of our knowledge, this is the first example of goldcatalyzed intramolecular reaction of cyclopropenes.

Synthetic utility of ammonium salts in a Cu-catalyzed three-component reaction as a facile coupling partner.

Abstract: Ammonium salts were found to be a convenient and inexpensive reagent in the Cu-catalyzed three-component reaction with terminal alkynes and sulfonyl or phosphoryl azides leading to N-unprotected amidines. Thus obtained amidines bearing 2-bromobenzenesulfonyl moiety were efficiently cyclized by the Cu-catalyzed intramolecular N-arylation to give an important pharmacophore skeleton of 2H-1,2,4-benzothiadiazine 1,1-dioxides. Conveniently, two tandem catalytic procedures could be readily operated in one pot.

Mechanistic Studies on the Catalytic Asymmetric Mannich-Type Reaction with Dihydroisoquinolines and Development of Oxidative Mannich-Type Reactions Starting from Tetrahydroisoquinolines

Abstract: Detailed mechanistic studies on our recently reported asymmetric addition reactions of malonates to dihydroisoquinolines (DHIQs) catalyzed by chiral Pd(II) complexes were carried out. It was found that an N,O-acetal was generated in situ by the reaction of DHIQ with (Boc)2O, and cooperative action of the Pd(II) complex as an acid−base catalyst allowed the formation of a chiral Pd enolate and a reactive iminium ion via α-fragmentation. The iminium ion was also accessible via oxidation with DDQ as an oxidant, and a catalytic asymmetric oxidative Mannich-type reaction was achieved with tetrahydroisoquinolines (THIQs) as starting materials. This oxidation protocol was applicable to N-acryloyl-protected THIQs, allowing the efficient synthesis of optically active tetrahydrobenzo[a]quinolizidine derivatives via intramolecular Michael reaction.

Gold(I)-catalyzed intramolecular hydroarylation of allenes.

Abstract: Gold(I) complexes react with 4-allenyl arenes in an exo fashion to furnish vinyl-substituted benzocycles. Phosphite gold(I) monocations were found to be optimal, and the catalyst was tolerant of ethers, esters, and pyrroles. Reactions proceeded in unpurified solvent at room temperature.

Intramolecular Pd(II)-catalyzed cyclization of propargylamides: straightforward synthesis of 5-oxazolecarbaldehydes.

Abstract: Direct synthesis of 2-substituted 5-oxazolecarbaldehydes was performed by intramolecular reaction of propargylamides through treatment with a catalytic amount of Pd(II) salts in the presence of a stoichiometric amount of reoxidant agent The heterocyclization process was well-tolerated by a wide range of aryl, heteroaryl, and alkyl propargylamides This protocol constitutes a valuable synthetic pathway to 5-oxazolecarbaldehydes, alternative to the formylation on oxazole rings, often unsatisfactory in term of regioselectivity and yields

Electrophilic ipso-cyclization of N-(p-methoxyaryl)propiolamides involving an electrophile-exchange process.

Abstract: A novel electrophilic ipso-cyclization involving an electrophile-exchange process has been developed. In the presence of CuX (X = I, Br, SCN) and electrophilic fluoride reagents, a variety of N-(p-methoxyaryl)propiolamides and 4-methoxyphenyl 3-phenylpropiolate were cyclized to selectively afford the corresponding spiro[4.5]decenones in moderate to good yields. It is noteworthy that two azaquaternary tricyclic products were synthesized through a two-step pathway involving an electrophilic ipso-cyclization and then an intramolecular Heck reaction.

Indium(III)-catalyzed tandem reaction with alkynylbenzaldehydes and alkynylanilines to heteroaromatic compounds.

Abstract: Starting from ortho-alkynylbenzaldehydes and ortho-alkynylanilines, In(OTf)3-catalyzed synthesis of ring-condensed heteroaromatic compounds was developed via a domino intramolecular nucleophilic attack/intermolecular cycloaddition/dehydration reaction.

One-step synthesis of substituted dihydro- and tetrahydroisoquinolines by FeCl3.6H2O catalyzed intramolecular Friedel-Crafts reaction of benzylamino-substituted propargylic alcohols.

Abstract: A mild, versatile, and efficient method for the one-step synthesis of substituted dihydro- and tetrahydroisoquinolines has been developed by the FeCl3·6H2O catalyzed intramolecular allenylation/cyclization reaction of benzylamino-substituted propargylic alcohols, representing the first example of the intramolecular Friedel−Crafts reaction of propargylic alcohols.

Investigations of glycosylation reactions with 2-N-acetyl-2N,3O-oxazolidinone-protected glucosamine donors.

Abstract: NIS/AgOTf-promoted glycosylations with ethyl 2,3-N,O-carbonyl-2-deoxy-1-thio-beta-D-glucopyranoside donors can be performed with either alpha- or beta-selectivity by tuning the reaction conditions. Small amounts of AgOTf (0.1 equiv) and short reaction times give beta-selectivity, whereas 0.4 equiv of AgOTf and prolonged reaction times afford alpha-linked products. NMR-monitored glycosylation and anomerization experiments show initial formation of exclusively the beta-linkage, which anomerizes, through an intramolecular mechanism involving an endocyclic C-O bond cleavage, to the alpha-linkage.

General access to the vinca and tacaman alkaloids using a Rh(II)-catalyzed cyclization/cycloaddition cascade.

Abstract: The total synthesis of several members of the vinca and tacaman classes of indole alkaloids has been accomplished. The central step in the synthesis consists of an intramolecular [3+2]-cycloaddition reaction of an α-diazo indoloamide which delivers the pentacyclic skeleton of the natural product in excellent yield. The acid lability of the oxabicyclic structure was exploited to establish the trans-D/E ring fusion of (±)-3H-epivincamine (3). Finally, a base induced keto-amide ring contraction was utilized to generate the E-ring of the natural product. A variation of the cascade sequence of reactions used to synthesize (±)-3H-epivincamine was also employed for the synthesis of the tacaman alkaloids (±)-tacamonine and (±)-apotacamine.

A General Synthetic Entry to the Pentacyclic Strychnos Alkaloid Family, Using a [4 + 2]-Cycloaddition/Rearrangement Cascade Sequence

Abstract: The total synthesis of (±)-strychnopivotine, (±)-tubifolidine, (±)-strychnine, and (±)-valparicine is reported. The central step in the synthesis consists of an intramolecular [4 + 2]-cycloaddition/rearrangement cascade of an indolyl-substituted amidofuran that delivers an aza-tetracyclic substructure containing the ABCE-rings of the Strychnos alkaloid family. A large substituent group on the amide nitrogen atom causes the reactive s-trans conformation of the amidofuran to be more highly populated, thereby facilitating the Diels–Alder cycloaddition. The reaction also requires the presence of an electron-withdrawing substituent on the indole nitrogen for the cycloaddition to proceed. The cycloaddition/rearrangement cascade was remarkably efficient given that two heteroaromatic systems are compromised in the reaction. Closure to the remaining D-ring of the Strychnos skeleton was carried out from the aza-tetracyclic intermediate by an intramolecular palladium-catalyzed enolate-driven cross-coupling between t...

Total synthesis of (S)-(+)-tylophorine via enantioselective intramolecular alkene carboamination.

Abstract: The enantioselective synthesis of (S)-(+)-tylophorine, a potent cancer cell growth inhibitor, has been accomplished in eight steps from commercially available 3,4-dimethoxybenzyl alcohol. A copper (II)-catalyzed enantioselective intramolecular alkene carboamination was employed as the key step to construct the chiral indolizidine ring.

New and Expeditious Tandem Sequence Aza-Michael/Intramolecular Nucleophilic Substitution Route to Substituted γ-Lactams : Synthesis of the Tricyclic Core of (±)-Martinellines

Abstract: A new and highly diastereoselective tandem reaction aza-Michael/intramolecular nucleophilic substitution is presented. This unprecedented tandem reaction between N-substituted α-bromoacetamides and Michael acceptors proceeds with good yields and excellent diastereoselectivity to provide the corresponding trisubstituted γ-lactam systems. An application to the concise synthesis of the tricyclic core of (±)-martinelline alkaloids is also described.

Domino Double Michael−Claisen Cyclizations: A Powerful General Tool for Introducing Quaternary Stereocenters at C(4) of Cyclohexane-1,3-diones and Total Synthesis of Diverse Families of Sterically Congested Alkaloids

Abstract: Reactions of substituted acetone derivatives with acrylic acid esters (>200 mol %) in the presence of t-BuOK (200 mol %) in t-BuOH-THF (1:1 by volume) turned out to proceed as a cascade process consisting of the first Michael addition, the second Michael addition, and the last Claisen reaction to afford 4,4-disubstituted cyclohexane-1,3-diones. Only more substituted enolates play the role of a Michael donor in this cascade process, and therefore the ketone took up two alkoxycarbonylethyl groups on the same carbon bearing more substituents. Such intermediates were followed by intramolecular Claisen reactions leading to cyclohexane-1,3-diones bearing quaternary stereogenic centers at C(4), which bears an alkoxycarbonylethyl group and the substituent of the starting acetone derivatives. Thus-obtained 4,4-disubstituted cyclohexane-1,3-diones were successfully employed for total syntheses of intricate alkaloids of biological interest such as (+)-aspidospermidine, (±)-galanthamine, (±)-lycoramine, and (±)-mesem...

Electrophilic ipso-Iodocyclization of N-(4-Methylphenyl)propiolamides : Selective Synthesis of 8-Methyleneazaspiro[4,5]trienes

Abstract: A novel and selective method for the synthesis of 8-methylenespiro[4,5]trienes via intramolecular electrophilic ipso-iodocyclization of N-(4-methylphenyl)propiolamides has been developed. In the presence of ICl or I2, 8-methylene-1-azaspiro[4,5]trienes were selectively prepared from the electrophilic ipso-iodocyclization of N-(4-methylphenyl)propiolamides in moderate to good yields.

Samarium(II)-Mediated Spirocyclization by Intramolecular Aryl Radical Addition onto an Aromatic Ring

Abstract: Samarium(II)-mediated spirocyclization by intramolecular addition of aryl radicals onto an aromatic ring was achieved by the reaction of N-(2-iodophenyl)-N-alkylbenzamides with SmI2 in the presence of HMPA, yielding spirocyclic indolin-2-one derivatives. The ether congeners afford spirocyclic benzofuran derivatives in moderate yields by aryl radical addition onto a benzene ring without having an electron-withdrawing group. The reaction with other aryl groups such as naphthalene and indole rings is also described.

Palladium-catalyzed intramolecular C-arylation of benzylic carbon: synthesis of 3-benzoxazolylisoindolinones by a sequence of Ugi-4CR/postfunctionalization.

Abstract: Submitting Ugi-adduct 4 to two consecutive metal-catalyzed intramolecular reactions, namely copper-catalyzed O-arylation and palladium-catalyzed C-arylation of benzylic carbon developed in the course of this study, affords the benzoxazolylisoindolinones in good to excellent yields.

Synthesis of (-)-Hamigeran B

Abstract: The synthesis of (−)-hamigeran B has been achieved, based on a new approach to cyclopentane construction, the rhodium-mediated intramolecular C−H insertion of α-aryl−α-diazoketones. The endo-isopropyl group was installed by selective hydrogenation of a cyclopropylidene substituent.

A Gold(I)‐Catalyzed Intramolecular Reaction of Propargylic/Homopropargylic Alcohols with Oxirane

Abstract: The gold(I)-catalyzed cycloisomerization of epoxy alkynes in the presence of nucleophile is an efficient protocol to provide ketal skeletons with high stereoselectivity. An intramolecular reaction of propargylic/homopropargylic alcohols with oxirane to produce ketal/spiroketals in moderate yields under mild conditions has been reported. Moreover, the mechanism of this kind of reaction has been discussed on the basis of a series of control and O-18 tracer experiments.