Synthesis of pyrido[1,2-b]indazoles via aryne [3 + 2] cycloaddition with N-tosylpyridinium imides

The [3 + 2] cycloaddition of arynes with N-tosylpyridinium imides, followed by an elimination of Ts(-), affords pyrido[1,2-b]indazoles under mild reaction conditions in good yields.     

A brand-new Pd-mediated generation of benzyne and its [2+2+2] cycloaddition: δ-carbon elimination and concomitant decarboxylation

We found a brand-new method for the generation of aryne from methyl 2-bromobenzoates via the Pd-mediated concomitant δ-carbon elimination and decarboxylation. The generated arynes underwent Pd-mediated [2+2+2] cycloaddition to give triphenylenes.     

苯炔与硝酮[3+2]环加成制备二取代苯并异噁唑烷

采用[3 2]1,3-偶极环加成反应,苯炔前体邻-三甲硅基苯酚三氟甲磺酸酯在氟化铯的作用下与硝酮反应合成了9个2,3-二取代苯并[d]异噁唑烷,收率87%～97%。其结构经1H NMR,13C NMR和高分辨率MS确证。     

Intramolecular [3 + 2]-cycloaddition reaction of push-pull dipoles across heteroaromatic pi-systems

[reaction: see text] Push-pull dipoles generated from the Rh(II)-catalyzed reaction of diazo imides containing tethered heteroaromatic rings undergo successful [3 + 2]-cycloaddition across the 2,3-pi-bond to provide novel pentacyclic compounds in good to excellent yields in a stereocontrolled fashion. The facility of the cycloaddition is critically dependent on conformational factors in the transition state.     

Organocatalytic Asymmetric Formal [3+2] Cycloaddition as a Versatile Platform to Access Methanobenzo[7]annulenes

Pharmaceutically and structurally important methanobenzo[7]annulenes were synthesized in very good yields with excellent enantio‐ and diastereoselectivities through an unprecedented organocatalytic formal [3+2] cycloaddition from readily available 2‐alkyl‐3‐hydroxynaphthalene‐1,4‐diones and alkyl vinyl ketones.     

Regio- and stereochemistry of the intramolecular [2+2] photoproducts from two related vinylogous imides

The regio- and stereochemistry of the intramolecular [2+2] photoproducts from two related vinylogous imides have been determined with the aid of X-ray crystallography; their chemistry and a mechanistic rationale of their formation are presented.     

Development of a [3+3] cycloaddition strategy toward functionalized piperidines

This paper describes a novel route to functionalized piperidines via a formal [3+3] cycloaddition reaction of activated aziridines and palladium-trimethylenemethane (Pd-TMM) complexes. The cycloaddition reaction generally proceeds enantiospecifically with ring opening at the least hindered site of the aziridine. Therefore, readily available enantiomerically pure 2-substituted aziridines can be utilized to prepare enantiomerically pure 2-substituted piperidines in good to excellent yield. The N-substituent on the aziridine proved to be crucial to the success of this reaction with only 4-toluenesulfonyl (Ts) and 4-methoxybenzenesulfonyl (PMBS) aziridines permitting smooth cycloaddition to take place. Additionally, spirocyclic aziridines have been found to participate in the [3+3] cycloaddition reaction, whereas 2,3-disubstituted aziridines can be applied to provide fused bicyclic piperidines, albeit in low yield.     

A 2:1 coupling reaction of arynes with aldehydes via o-quinone methides: straightforward synthesis of 9-arylxanthenes

[reaction: see text] A novel coupling reaction, where an aldehyde and two molar amounts of an aryne are assembled selectively, has been demonstrated to afford diverse 9-arylxanthene derivatives in one step. o-Quinone methide arising from the [2 + 2] cycloaddition of an aldehyde with an aryne was postulated as a transient intermediate.     

Lewis acid-catalyzed intermolecular [4 + 2] cycloaddition of 3-alkoxycyclobutanones to aldehydes and ketones

Intermolecular [4 + 2] cycloaddition between 3-alkoxycyclobutanones and aldehydes or ketones by the activation with boron trifluoride etherate is reported. The carbonyl compounds are inserted into the less substituted C2-C3 bond of the cyclobutanone ring of 6-alkyl-2-oxabicyclo[4.2.0]octan-7-ones to afford 1-alkyl-5,7-dioxabicyclo[4.4.0]decan-2-one derivatives regioselectively (>99:1) and diastereoselectively. On the other hand, [4 + 2] cycloaddition of 3-ethoxy-2,2-dialkylcyclobutanones at low temperature proceeds at the more substituted C2-C3 bond to yield 3,3-dialkyl-6-ethoxy-2,3,5,6-tetrahydro-4H-pyran-4-one derivatives with high regioselectivities. This [4 + 2] cycloaddition is developed into a one-pot synthesis of tri- or tetrasubstituted dihydro-gamma-pyrones from 3-ethoxycyclobutanones which are readily prepared from acid chloride and ethyl vinyl ether. The two regioselectivities observed in ring-opening of cyclobutanones can ascribe to thermodynamic stabilities of zwitterionic intermediates generated from tetrahydropyran-fused cyclobutanones and 3-ethoxycyclobutanones.     

Rearrangement of a mesylate tropane intermediate in nucleophilic substitution reactions. Synthesis of aza-bicyclo[3.2.1]octane and aza-bicyclo[3.2.2]nonane ethers,imides, and amines

Nucleophilic substitution of 2beta-mesyloxymethyl-N-methyl-3beta-p-tolyl-tropane intermediate with alkoxides, metal imides, or amines was found to lead not only to the expected bicyclo[3.2.1]octane (tropane) ether, imide, and amine derivatives but also to unexpected bicyclo[3.2.2]nonane derivatives. When alkoxides were used as nucleophile, only the rearranged bicyclo[3.2.2]nonane structure was obtained, whereas the use of amines or imides as nucleophile afforded a mixture of the two structures. The bicyclo[3.2.2]nonane structure was assigned by NMR analysis.     

Highly Regio-, Diastereo-, and Enantioselective Synthesis of Tetrahydroazepines and Benzo[b]oxepines through Palladium-Catalyzed [4+3] Cycloaddition Reactions

A novel Pd⁰-catalyzed asymmetric [4+3] annulation reaction of two readily accessible starting materials has been developed for building seven-membered heterocyclic architectures. The potential [3+2] side pathway could be suppressed though fine tuning of the conditions. A broad scope of cycloaddition donors and acceptors participated in the transformation with excellent chemo-, regio-, diastereo-, and enantioselectivtities, leading to valuable tetrahydroazepines and benzo[b]oxepines.     

Rhodium N-heterocyclic carbene-catalyzed [4 + 2] and [5 + 2] cycloaddition reactions

[reactions: see text] A rhodium complex of N-heterocyclic carbene (NHC) has been developed for intra- and intermolecular [4 + 2] and intramolecular [5 + 2] cycloaddition reactions. This is the first use of a transition-metal NHC complex in a Diels-Alder-type reaction. For the intramolecular [4 + 2] cycloaddition reactions, all the dienynes studied were converted to their corresponding cycloadducts in 91-99% yields within 10 min. Moreover, up to 1900 turnovers have been obtained for the intramolecular [4 + 2] cycloaddition at 15-20 degrees C. For the intermolecular [4 + 2] cycloadditions, high yields (71-99%) of the corresponding cycloaddition products were obtained. The reaction time and yield were highly dependent upon the diene and the dienophile. For the intramolecular [5 + 2] cycloaddition reactions, all the alkyne vinylcyclopropanes studied were converted to their corresponding cycloadducts in 91-98% yields within 10 min. However, the catalytic system was not effective for an intermolecular [5 + 2] cycloaddition reaction.     

Synthesis of new functionalized 3,7-diazabicyclo[3.3.1]nonanes by aminomethylation of the Guareschi imides

The aminomethylation of 4,4-dialkyl-2,6-dioxopiperidine-3,5-dicarbonitriles (Guareschi imides) was studied for the first time. When the Guareschi imides were treated with primary aliphatic amines and an excess of formaldehyde, 2,4-dioxo-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarbonitriles were obtained in varying yields (15–67%). The structure of 9,9-dimethyl-7-(2-methylpropyl)-2,4-dioxo-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarbonitrile was studied by X-ray diffraction analysis.     

Rh-catalyzed [5+1] and [4+1] cycloaddition reactions of 1,4-enyne esters with CO: a shortcut to functionalized resorcinols and cyclopentenones

We have developed novel Rh-catalyzed [n+1]-type cycloadditions of 1,4-enyne esters, which involve an acyloxy migration as a key step. The efficient preparation of functionalized resorcinols, including biaryl derivatives, from readily available 1,4-enyne esters and CO was achieved by Rh-catalyzed [5+1] cycloaddition accompanied by 1,2-acyloxy migration. When enyne esters had an internal alkyne moiety, the reaction proceeded by a [4+1]-type cycloaddition involving 1,3-acyloxy migration, leading to cyclopentenones.     

Synthesis of [1,3]dithiole and spiro[1,3]dithiole thiopyran derivatives of the [1,2]dithiolo[1,4]thiazine ring system

We report the synthesis of some new polysulfur-nitrogen heterocycles by cycloaddition reactions to readily available tricyclic condensed 1,2-dithiole-3-thiones. Thus, treatment of bis[1,2]dithiolopyrrole ketothione 1 with diacyl acetylenes gave the bis-aducts 2a-d. On the other hand, cycloaddition of bis[1,2]dithiolo[1,4]thiazine ketothione 3 with 1 equiv of acyl or diacyl acetylenes gave [1,3]dithiolylidenyl[1,2]dithiolo[1,4]thiazines 4a-f in fair to high yields. Catalysis by scandium triflate was used in the reactions that implied the less reactive dipolarophiles. Treatment of 3 with 2 equiv of DBA gave the bis-aduct 5a, and reaction of 4c with DMAD gave the mixed bis-adduct 5b. Cyclic voltammetry of selected examples showed irreversible processes that were influenced by the electrochemical activity of peripheral groups bonded to the heterocyclic system.     

Highly enantioselective Ag(i)-catalyzed [3 + 2] cycloaddition of azomethine ylides

A highly reactive Ag(I)-catalyzed [3 + 2] cycloaddition of azomethine ylides is founded using AgOAc as the catalytic precursor and phosphines as ligands. Using a new bis-ferrocenyl amide phosphine (FAP) as the ligand, we found that high enantioselectivities (up to 97% ee) have been achieved in the [3 + 2] cycloaddition of azomethine ylides. Up to four stereogenic centers can be established in this multicomponent coupling reaction from readily available materials such as aldehydes, aminoesters, and dipolarophiles.     

Rhodium‐Catalyzed Intramolecular [3+2+2] Cycloadditions between Alkylidenecyclopropanes,Alkynes, and Alkenes

A Rh‐catalyzed intramolecular [3+2+2] cycloaddition is reported. The cycloaddition affords synthetically relevant 5,7,5‐fused tricyclic systems of type 2 from readily available dienyne precursors. The transformation takes place with moderate or good yields, high diastereoselectivity, and total chemoselectivity.     

Asymmetric synthesis of bicyclo[4.3.1]decadienes and bicyclo[3.3.2]decadienes via [6 + 3] trimethylenemethane cycloaddition with tropones

The cyanosubstituted trimethylenemethane donor undergoes palladium-catalyzed [6 + 3] cycloaddition with a variety of tropones to yield bicyclo[4.3.1]decadienes in excellent regio-, diastereo-, and enantioselectivity. Products of the Pd-TMM [6 + 3] cycloaddition participate in a thermal [3,3] sigmatropic rearrangement to yield bicyclo[3.3.2]decadienes in good yield.     

Regiodivergent Intermolecular [3+2] Cycloadditions of Vinyl Aziridines and Allenes: Stereospecific Synthesis of Chiral Pyrrolidines

The first rhodium‐catalyzed intermolecular [3+2] cycloaddition reaction of vinyl aziridines and allenes for the synthesis of enantioenriched functionalized pyrrolidines was realized. [3+2] cycloaddition with the proximal C=C bond of N‐allenamides gave 3‐methylene‐pyrrolidines in high regio‐ and diastereoselectivity, whereas, 2‐methylene‐pyrrolidines were obtained as the major products by the cycloadditions of vinyl aziridines with the distal C=C bond of allenes. Use of readily available starting materials, a broad substrate scope, high selectivity, mild reaction conditions, as well as versatile functionalization of the cycloadducts make this approach very practical and attractive.     

Synthesis of bicyclic pyrane derivatives via tungsten-mediated [3 + 3] cycloaddition of epoxides with tethered alkynes.

Propargyltungsten compounds bearing a tethered epoxide were prepared in short steps from readily available materials. In the presence of various Lewis acids, BF(3).Et(2)O catalysts (25 mol %) most effectively promote the [3 + 3] cycloaddition of the epoxide with its tethered propargyltungsten group, delivering bicyclic pyranyltungsten compounds in reasonable yields. This cyclization proceeds highly diastereoselectively with tolerance of various functional groups. The stereochemical outcome indicates that the cycloaddition is initiated by the ring opening of the epoxides via an exo-attack of the propargyltungsten group. The resulting pyranyltungsten organometallics were demetalated to yield various bicyclic pyranyl derivatives using different oxidants. This new method provides a short enantiospecific synthesis of bicyclic oxygen compounds if chiral epoxide is used in the cyclization. A mechanistic model is presented to rationalize the reaction pathway of this [3 + 3] cycloaddition.