Synthesis of dihydrobenzisoxazoles by the [3 + 2] cycloaddition of arynes and oxaziridines

Dihydrobenzisoxazoles are readily prepared in good yields by the [3 + 2] cycloaddition of oxaziridines and arynes. The reaction involves an unusual cleavage of the C-O bond of the oxaziridine and tolerates a variety of substituents on the oxaziridine and the o-(trimethylsilyl)aryl triflate to form aryl-, heteroaryl-, alkyl-, and naphthyl-substituted dihydrobenzisoxazoles. The resulting halogen-substituted dihydrobenzisoxazoles are readily elaborated to more complex products using palladium-catalyzed crossing-coupling processes.     

Synthesis of silafluorenes by iridium-catalyzed [2 + 2 + 2] cycloaddition of silicon-bridged diynes with alkynes

[reaction: see text] Silicon-bridged 1,6-diynes underwent [2 + 2 + 2] cycloaddition with alkynes in the presence of an iridium(I)-phosphine catalyst to afford densely substituted silafluorene derivatives. Extended silafluorene skeletons were constructed by the [2 + 2 + 2] cycloaddition of tetraynes.     

Nickel-mediated regioselective [2 + 2 + 2] cycloaddition of carboryne with alkynes

Transition metal-benzyne complexes have found many applications in organic synthesis, mechanistic studies, and the synthesis of functional materials. In sharp contrast, the chemistry of transition metal-carboryne complexes, especially late transition metal complexes, is virtually unknown. This communication reports a novel nickel-mediated regioselective [2 + 2 + 2] cycloaddition reaction of carboryne with alkynes via the Ni-carboryne intermediate (eta2-C2B10H10)Ni(PPh3)2. Because of the bulkiness of the carborane moiety, a high regioselectivity was achieved in the reactions involving unsymmetrical alkynes. This work furnishes a novel method for the preparation of highly substituted benzocarboranes which are difficult to obtain by other methods.     

Microwave-assisted iridium-catalyzed [2+2+2] cycloaddition of resin-bound dipropargylamine with alkynes

The [Ir(COD)Cl]₂/dppe system effectively catalyzes the solid-phase [2+2+2] cycloaddition of resin-bound dipropargylamine with alkynes under microwave conditions. The reaction results in high purity of isoindoline derivatives with moderate yields.     

Stereoselective [3+2+2] cycloaddition utilizing optically active binuclear Fischer carbene complexes with alkynes

The reaction of optically active α,β-unsaturated binuclear Fischer carbene complexes with alkynes gave planar chiral cycloheptatriene chromium complexes via [3+2+2] cycloaddition with high diastereoselectivity.     

Rhodium-catalyzed [2 + 2 + 2] cycloaddition of alkenyl isocyanates and alkynes

A rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition between alkenyl isocyanates and alkynes has been developed. Heating a mixture of an alkenyl isocyanate and a symmetrical internal alkyne in the presence of [Rh(ethylene)2Cl]2/P(4-OMe-C6H4)3 in toluene delivers substituted indolizinones and quinolizinones. Depending on the substrates, a rare fragmentation of the isocyanate unit can be involved within the cycloaddition process to furnish a vinylogous amide embedded in the indolizinone.     

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.     

Ligand-induced acceleration of the intramolecular [3 + 2] cycloaddition between alkynes and alkylidenecyclopropanes

[chemical reaction: see text]. Bulky phosphite L6 and several sterically robust phosphoramidites are excellent ligands for promoting the Pd-catalyzed [3 + 2] intramolecular cycloaddition between alkylidenecyclopropanes and alkynes. The use of these ligands allows for low catalyst loadings and facilitates the otherwise sluggish cycloaddition of hept-6-ynylidenecyclopropane systems.     

Synthesis of 2H-indazoles by the [3 + 2] dipolar cycloaddition of sydnones with arynes

A rapid and efficient synthesis of 2H-indazoles has been developed using a [3 + 2] dipolar cycloaddition of sydnones and arynes. A series of 2H-indazoles have been prepared in good to excellent yields using this protocol, and subsequent Pd-catalyzed coupling reactions can be applied to the halogenated products to generate a structurally diverse library of indazoles.     

Synthesis of conformationally restricted nicotine analogues by intramolecular [3+2] cycloaddition

We describe the synthesis of a series of conformationally constrained nicotine analogues 2-5 from appropriate pyridine-containing enals, featuring an intramolecular azomethine ylide-alkene [3+2] cycloaddition. The objective of the current project is to develop new selective nAChRs-targeting ligands. Of the nicotine analogues that we have studied, the conformation-restricting ring B unit can be either a five-membered carbocycle, or a six-membered carbocycle or heterocycle. The present work constitutes a general method for rapid assembly of other related tricyclic nicotine analogues.     

o-Dihaloarenes as aryne precursors for nickel-catalyzed [2 + 2 + 2] cycloaddition with alkynes and nitriles

o-Dihaloarenes acting as aryne precursors react with acetylenes and nitriles catalyzed by the NiBr(2)(dppe)/dppe/Zn system to give substituted naphthalene, phenanthridine or triphenylene derivatives depending on the reaction conditions in moderate to excellent yields with good tolerance of functional groups.     

Dehydrogenative [4 + 2] cycloaddition of formamides with alkynes through double C-H activation

Formamides having 1-arylalkyl groups on nitrogen undergo an unprecedented dehydrogenative [4 + 2] cycloaddition reaction with alkynes via nickel/AlMe(3) cooperative catalysis to give highly substituted dihydropyridone derivatives in good yields. Notably, the transformation proceeds through double functionalization of C(sp(2))-H and C(sp(3))-H bonds in the formamides.     

Catalytic enantioselective intermolecular [2 + 2 + 2] cycloaddition of an alkene and two alkynes

A catalytic enantioselective intermolecular [2 + 2 + 2] cycloaddition of one molecule of alkene (enone) and two molecules of alkyne was developed in the presence of a nickel complex modified by chiral monodentate oxazoline ligands, which have not previously been used as chiral ligands for transition metals in asymmetric catalysts, and an aluminium phenoxide.     

Rhodium-catalyzed chemo-, regio-, and enantioselective [2 + 2 + 2] cycloaddition of alkynes with isocyanates

[reaction: see text] We have developed a cationic rhodium(I)/modified-BINAP complex-catalyzed chemoselective [2 + 2 + 2] cycloaddition of alkynes with isocyanates leading to a wide range of 2-pyridones. This method was successfully applied to the chemo-, regio-, and enantioselective synthesis of axially chiral 2-pyridones from unsymmetrical alpha,omega-diynes, bearing an ortho-substituted phenyl at one terminal position, and alkyl isocyanates.     

Synthesis of novel isoxazolines and isoxazoles of N-substituted pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives through [3+2] cycloaddition

3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one 3 was prepared by an intramolecular cyclization of N-(4-cyano-3-methyl-1-phenyl-1H-pyrazol-5-yl) acetamide 2 in ethanol in the presence of piperidine. N-allylation and N-propargyl alkylation of N-substituted pyrazolo[3,4-d] pyrimidin-4(5H)-one 3 yielded the corresponding dipolarophiles 4 and 5 which afford by condensation with arylnitrile oxides in toluene the expected new isoxazolines 6 and isoxazoles 7, respectively. On the other hand, the aminopyrazole 1 in refluxing with ethanol in the presence of sodium hydroxide afforded the corresponding carboxamide 8, which then, was converted to its ethyl 3-methyl-4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d] pyrimidine-6-carboxylate 9 with neat diethyl oxalate. The dipolarophile 10 on regiospecific 1,3-dipolar cycloaddition with arylnitrile oxides affords isoxazoles 11 and the unexpected deethoxycarbonylated isoxazoles 12. The target compounds were completely characterized by ¹H NMR, ¹³C NMR, IR and HRMS.     

Cyclopentadienone synthesis by rhodium(I)-catalyzed [3 + 2] cycloaddition reactions of cyclopropenones and alkynes

The Rh(I)-catalyzed [3 + 2] cycloaddition of cyclopropenones and alkynes is found to provide a highly efficient and regiocontrolled route to cyclopentadienones (CPDs), building blocks of widespread use in the synthesis of natural and non-natural products, therapeutic leads, polymers, dendrimers, devices, and antigen presenting scaffolds. The versatility of the method is explored with 23 examples representing a wide range of alkyne variations (arylalkyl-, dialkyl-, heteroarylalkyl-) and diaryl- as well as arylalkylcyclopropenones. The reactions often proceed in high yield using minimal catalyst loadings and in all cases examined proceed with high or complete regioselectivity. The reaction is readily scalable to produce gram quantities of cycloadduct and provides a unique and versatile route to CPDs that would be otherwise difficult to obtain.     

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.     

Preparation of 3-azabicyclo [3.2.0] heptenones by intramolecular [2+2] cycloaddition

Pyrolysis of N-allyl enaminoesters is a general method for the stereoselective synthesis of 3-azabicyclo[3.2.0] heptenones ; the reaction involves a [2+2] intramolecular cycloaddition of an intermediate iminoketene.     

Regioselective rhodium-catalyzed intermolecular [2+2+2] cycloaddition of alkynes and isocyanates to form pyridones

A highly regioselective rhodium-catalyzed intermolecular [2+2+2] cycloaddition of terminal alkynes with a variety of isocyanates to provide 2- and 4-pyridones has been developed. This reaction proceeds in good to excellent yields and overcomes the problem of dimerization and trimerization through the use of phosphoramidite ligands. A CO migration in the metallacycle is proposed to account for the formation of 4-pyridone.