Bromination of 7-norbornene derivatives revisited: failure of a computational NMR method in elucidating the configuration of an organic structure.

Previously we reported on the bromination of 7-bromonorbornene at different temperatures yielding mixtures of addition products. The structural elucidations of the formed compounds were achieved by NMR spectroscopy. Particularly, the γ-gauche effect and long-range couplings were instrumental in assigning the stereochemistry of the adducts.

Nucleophilic and electrophilic cyclization of -alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties.

Intramolecular nucleophilic and electrophilic cyclization of alkyne-substituted pyrrole esters is described. Efficient routes towards the synthesis of pyrrolopyrazinone, pyrrolotriazinone and pyrrolooxazinone have been developed. First, -alkyne-substituted pyrrole ester derivatives were synthesized.

Synthesis of Pyrrole-Fused C,N-Cyclic Azomethine Imines and Pyrazolopyrrolopyrazines: Analysis of Their Aromaticity Using Nucleus-Independent Chemical Shifts Values.

The AgOTf-catalyzed reaction of C-2 substituted pyrrole hydrazones having an N-propargyl group was studied. The selective 6-endo-dig mode of cyclization was observed, giving rise to the formation of pyrrole-fused C,N-cyclic azomethine imine derivatives. The reaction of one azomethine imine derivative with various dipolarophiles resulted in the formation of cycloadducts having a pyrazolopyrrolopyrazine skeleton.

Intramolecular Gold-Catalyzed and NaH-Supported Cyclization Reactions of N-Propargyl Indole Derivatives with Pyrazole and Pyrrole Rings: Synthesis of Pyrazolodiazepinoindole, Pyrazolopyrazinoindole, and Pyrrolopyrazinoindole.

Gold-catalyzed and NaH-supported intramolecular cyclization of N-propargyl indole derivatives with pyrazole and pyrrole units attached to indole is described. An efficient route to the synthesis of pyrazolodiazepinoindole, pyrazolopyrazinoindole, and pyrrolopyrazinoindole has been established. First, N-propargyl 2-(1H-pyrazol-5-yl)-1H-indole and 2-(1H-pyrrol-2-yl)-1H-indole were synthesized.

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products.

Various N-propargylpyrrole and indolecarboxylic acids were efficiently converted into 3,4-dihydropyrrolo- and indolo-oxazin-1-one derivatives by a gold(III)-catalyzed cyclization reaction. Some of the products underwent TFA-catalyzed double bond isomerization and some did not. Cyclization reactions in the presence of alcohol catalyzed by Au(I) resulted in the formation of hemiacetals after cascade reactions.

Gold-catalyzed oxime-oxime rearrangement.

The gold-catalyzed reaction of pyrrole and indole oximes having a propargyl group attached to the nitrogen atom was studied. The selective 6-endo-dig mode of cyclization was observed for the terminal alkynes giving rise to the formation of pyrazine N-oxides in the presence of a gold catalyst. However, the reaction with substituted alkyne transferred the oxime functionality intramolecularly from one carbon atom to another via the 7-endo-dig cyclization process.

Design of pyrazolo-pyrrolo-pyrazines and pyrazolo-pyrrolo-diazepines via AuCl₃-catalyzed and NaH-supported cyclization of N-propargyl pyrazoles.

A concise synthetic methodology for new heterocyclic scaffolds, such as pyrazolo-pyrrolo-pyrazine and pyrazolo-pyrrolo-diazepine skeletons, was developed. The key features of this method include (i) synthesis of pyrrole-derived α,β-alkynyl ketones, (ii) introduction of various substituents into the alkyne functionality by Sonogashira cross-coupling, (iii) synthesis of pyrazole units by the reaction of α,β-alkynyl compounds with hydrazine monohydrate, (iv) gold-catalyzed cyclization of pyrazoles with alkyne units, and (v) cyclization with NaH. Furthermore, this methodology allows various substituents to be introduced into all positions of the target compounds.

Intramolecular heterocyclization of O-propargylated aromatic hydroxyaldehydes as an expedient route to substituted chromenopyridines under metal-free conditions.

A concise and regioselective approach to the synthesis of chromenopyridine and chromenopyridinone derivatives was developed. The synthetic strategy relies on the O-propargylation of aromatic hydroxyaldehydes followed by reaction with propargylamine. The intramolecular cycloaddition reaction between the alkyne and azadiene, which is formed as an intermediate, furnished the desired skeletons.

Trisequential photooxygenation reaction: application to the synthesis of carbasugars.

4,5-Dimethylenecyclohex-1-ene was subjected to a photooxygenation reaction to introduce oxygen functionalities. The endoperoxide obtained underwent an ene-reaction to form hydroperoxides with 1,3-diene structures. Further addition of singlet oxygen to the diene units resulted in the formation of tricyclic hydroperoxides having three oxygens in the molecule.

Design and synthesis of pyrrolotriazepine derivatives: an experimental and computational study.

The pyrrole derivatives having carbonyl groups at the C-2 position were converted to N-propargyl pyrroles. The reaction of those compounds with hydrazine monohydrate resulted in the formation of 5H-pyrrolo[2,1-d][1,2,5]triazepine derivatives. The synthesis of these compounds was accomplished in three steps starting from pyrrole.

Stereoselective syntheses of racemic quercitols and bromoquercitols starting from cyclohexa-1,4-diene: gala-, epi-, muco-, and neo-quercitol.

The efficient synthesis of gala-, epi-, neo-, and muco-quercitols and some brominated quercitols starting from cyclohexa-1,4-diene is reported. Treatment of the dibromide, obtained by the addition of bromine to cyclohexa-1,4-diene, with m-chloroperbenzoic acid (m-CPBA) yielded the dibromoepoxide, which was successfully converted to the desired dibromodiol by treatment with sulfuric acid. The resulting diol was reacted with 2,2-dimethoxypropane to give the dibromoketal.

Design, synthesis, and biological activities of some branched carbasugars: construction of a substituted 6-oxabicyclo[3.2.1]nonane skeleton.

Transformation of cyclohexa-2,4-diene-1,2-diylbis(methylene) diacetate to various carbasugars is described. Photooxygenation of a cyclohexadiene derivative gave a bicyclicendoperoxide, which was reduced with thiourea to [2-[(acetyloxy)methyl]cyclohexa-2,4-dien-1-yl]methyl acetate. Epoxidation of the remaining double bond followed by epoxide ring-opening and hydrolysis of the acetate groups gave one of the target hexols.

Synthesis of bishomoinositols and an entry for construction of a substituted 3-oxabicyclo[3.3.1]nonane skeleton.

1,3,3a,7a-Tetrahydro-2-benzofuran was used as key compound for the synthesis of various bishomoinositol derivatives. The diene was subjected to an epoxidation reaction for further functionalization of the diene unit. The bisepoxide obtained was submitted to a ring-opening reaction with acid in the presence of water.

Palladium-catalyzed formation of oxazolidinones from biscarbamates: a mechanistic study.

Oxazolidinones can be synthesized starting from cyclic biscarbamates via a palladium-catalyzed reaction. To test the proposed mechanism of this reaction, first, bicyclonorcarene endoperoxides derived from cyano and carbomethoxy cycloheptatrienes were synthesized and converted into the corresponding diols. The reaction of diols with toluenesulfonyl isocyanate followed by a palladium catalyzed reaction furnished oxazolidinone derivatives in similar yields.

Endo- and exo-configured cyclopropylidenes incorporated into the norbornadiene skeleton: generation, rearrangement to allenes, and the effect of remote substituents on carbene stability.

For the synthesis of endo-configured cyclopropylidenes annelated to benzonorbornadiene, first the exo-bridge hydrogen in benzonorbornadiene was blocked with ethyl, bromine, and methoxy groups. All efforts to add dichloro-, dibromo-, or fluorobromocarbenes to ethylbenzonorbornadiene failed. However, addition of fluorobromocarbene to bromo- or methoxybenzonorbornadiene gave the corresponding cyclopropane derivatives bearing two halogen atoms, which were submitted to the Doering-Moore-Skattebøl reaction.

Synthesis of bromo-conduritol-B and bromo-conduritol-C as glycosidase inhibitors.

For the synthesis of bromo-conduritol-B skeleton, bromo-1,4-benzoquinone was subjected to bromination followed by the reduction of the carbonyl groups with NaBH(4). Substitution of bromides bonded to sp(3)-hybridized carbon atoms with AgOAc gave the bromo-conduritol-B tetraacetate in high yield. For the construction of bromo-conduritol-C skeleton, 2,2-dimethyl-3a,7a-dihydro-1,3-benzodioxole was used as the starting material.

rac-(2R*,3S*,5S*,6R*,7S*,8S*)-7,8-Dichloro-bicyclo-[2.2.2]octane-2,3,5,6-tetrayl tetra-acetate.

The title compound, C(16)H(20)Cl(2)O(8), contains a central bicyclo-[2.2.2]octane skeleton with slightly twisted conformation.

Stereoselective synthesis of bishomo-inositols as glycosidase inhibitors.

For the synthesis of various bishomo-inositol derivatives, 1,3,3a,7a-tetrahydro-2-benzofuran was used as the key compound. For further functionalization of the diene unit, the diene was subjected to photooxygenation, epoxidation, and cis-hydroxylation reactions. The endoperoxide linkage was cleaved by thiourea.

Substituent effects on the ring-opening mechanism of lithium bromocyclopropylidenoids to allenes.

The ring-opening reactions of lithium bromocyclopropylidenoids to allenes have been investigated computationally at the B3LYP/6-31G(d) level of theory. Formally, two pathways can be considered: the reaction may either proceed in a concerted fashion or stepwise with the intermediacy of a free cyclopropylidene. In both cases, the loss of the bromide ion determines the kinetic of the reaction.

Synthesis of bicyclo[2.2.2]octane-2,3,5,6,7,8 hexols (Bishomoinositols) as glycosidase inhibitors.

For the construction of the bicyclo[2.2.2]octane skeleton, 2,2-dimethyl-3a,7a-dihydro-1,3-benzodioxole was reacted with vinylene carbonate to give two isomeric cycloadditon products having the bicyclo[2.

The effect of the double bond pyramidalization on the mode of the bromination reaction: bromination of benzobicyclononadiene.

The bromination of 6,7,8,9-tetrahydro-5H-5,9-ethenobenzo[a][7]annulene yielded regio- and stereospecifically formed dibromides arising from the alkyl shift where the bromine exclusively attacks the double bond from the endo face of the double bond. DFT calculations on model compounds showed that the pyramidalization of the double bond and steric repulsion caused by the methylene protons are responsible for the stereo- and regioselective addition of bromine.

Unusual manganese(III)-mediated oxidative free radical additions of 1,3-dicarbonyl compounds to benzonorbornadiene and 7-heterobenzonorbornadienes: mechanistic studies.

Benzonorbornadiene and heterobenzonorbornadiene were reacted with dimedone/acetylacetone and Mn(OAc)3 in the presence and absence of Cu(OAc)2. The reaction of benzonorbornadiene with dimedone gave mainly the dihydrofuran addition product, whereas the reaction with acetylacetone produced a rearranged product in addition to the dihydrofuran derivative. On the other hand, oxanorbornadiene gave unusual products such as the cycloproponated compound and a product arising from the incorporation of 2 mol of dimedone.

(1SR,2SR,3SR,4RS,5RS,6RS,7SR,8RS)-7,8-Dichlorobicyclo[4.2.0]octa-2,3,4,5-tetrayl tetraacetate.

In the title compound, C(16)H(20)Cl(2)O(8), the bicyclic system contains a central non-planar cyclohexane ring which is fused to a cyclobutane moiety. The cyclohexane ring has a chair conformation and the whole system adopts a syn conformation. The structure provides information on the stereochemical course of the chlorination, photo-oxidation and hydroxylation steps of the reaction.

Stereospecific synthesis of a new class of compounds: bis-homoconduritol-A, -D, and -F.

Bis-homoconduritol derivatives with conduritol-A, -D, and -F structures have been synthesized starting from cyclooctatetraene. The photooxygenation of trans-7,8-dibromo- and cis-7,8-dichlorobicyclo[4.2.

Synthesis and structure of cyclopropano-annelated homosesquinorbornene derivatives containing pyramidalized double bonds: evidence for the sterical effect of a cyclopropyl group on the degree of C=C double-bond pyramidalization.

[reaction: see text] endo- and exo-2,3,4,7-tetrahydro-1H-1,4-methanobenzocycloheptene-7-carboxylic acid ethyl esters have been synthesized, and their Diels-Alder cycloaddition reactions with maleic anhydride, dimethyl acetylenedicarboxylate and singlet oxygen have been investigated. The X-ray analysis of four adducts indicated the pyramidalization of the central double bond. Density functional theory calculations on the isolated products and model compounds showed excellent agreement between the experimental and theoretical determined butterfly angles.