Synthesis and properties of azoles and their derivatives. 37. Synthesis of 3,5-disubstituted 1,2,4-oxadiazoles containing indole radicals

The 1,3-dipolar cycloaddition of nitrile N-oxides to indole nitriles yields 3,5-di-substituted 1,2,4-oxadiazoles containing an indole radical at the 5 position. Condensation of amidoximes with indole iminoester hydrochlorides yields 1,2,4-oxadiazoles having an indole segment at the 3 and/or 5 position of the oxadiazole ring. Pyrolysis of O-acyl derivatives of indole amidoximes yields 1,2,4-oxadiazoles with an indole residue at the 3 position.For Communication 36, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1609–1615, December, 1984.     

From cyclopentadiene to isoxazoline-carbocyclic nucleosides: a rapid access to biological molecules through nitrosocarbonyl chemistry

A rapid access to carbocyclic nucleosides containing a fused isoxazoline ring is proposed starting from cyclopentadiene. The route involves an hetero Diels-Alder cycloaddition reaction of nitrosocarbonylbenzene followed by a 1,3-dipolar cycloaddition of nitrile oxides, cleavage of the N-O tether and elaboration of the heterocyclic aminols into nucleosides via linear construction of purine and pyrimidine heterocycles.     

A regioselective cycloaddition route to isoxazoleboronic esters

Alkynylboronates participate in 1,3-dipolar cycloaddition reactions with nitrile oxides to provide isoxazoleboronic esters with excellent levels of regiocontrol; additionally, these potentially valuable synthetic intermediates have been shown to participate efficiently in Suzuki coupling reactions.     

Synthesis of a new class of keto-linked bis heterocycles

A new class of keto-linked bis heterocycles have been prepared by 1,3-dipolar cycloaddition of tosyl methyl isocyanide, nitrile imines and nitrile oxides to unsymmetrical bischalcones.     

Nitrile Imines: From Matrix Characterization to Stable Compounds

The concept of 1,3-dipolar cycloaddition was developed, starting in the late 1950s, largely by Rolf Huisgen and his students in Munich, and it has led to one of the most versatile methods for the construction of five-membered ring heterocycles. Although first known only as transient intermediates, nitrile imines have been at the heart of mechanistic studies of this type of cycloaddition reactions. Hundreds of mechanistic papers appeared in 1960s and 1970s; reliable spectroscopic observations were achieved in the early 1980s both at low temperatures and in the gas phase; finally, the first crystalline nitrile imine was reported in 1988. The unusual structures found by X-ray analyses as well as the facile rearrangements observed experimentally have fostered a new interplay between experiment and theory. The story of nitrile imines, from matrix characterization to stable compounds, nicely illustrates the role that main group elements can play in organic chemistry.     

Triptycene quinones in synthesis: preparation of triptycene cyclopentenedione and its reactivity as a dienophile

Triptycenene quinone 1 was converted to triptycene cyclopentenedione 5 through hydroxyquinone-phenyliodonium ylide formation and thermal ring contraction of the latter. Cyclopentenedione 5 reacts as a dienophile and as a dipolarophile with dienes and nitrile oxides, affording polycyclic adducts bearing the triptycene moiety.     

Variable Markovnikov orientation and "cis effect" in ene reactions of nitrosocarbonyl intermediates

Nitrosocarbonyl intermediates, generated at room temperature by the mild oxidation of nitrile oxides, undergo clean ene reactions with trisubstituted olefins. Allylic hydrogens on the more congested side of the alkene are exclusively abstracted (the "cis effect"), thus resembling singlet oxygen behavior. Nitrosocarbonyl benzene follows a Markovnikov orientation and abstracts preferentially the twix hydrogens over the lone ones. With the more sterically demanding nitrosocarbonyl mesitylene, the Markovnikov directing effect is relieved, and comparable twix and lone abstraction are observed.     

Trapping the elusive aza-oxyallylic cation: new opportunities in heterocycloaddition chemistry

The aza-oxyallylic cation is a reactive intermediate that undergoes a [4+3] cycloaddition with dienes to form seven-membered heterocycles. Although this type of intermediate was proposed over 50 years ago, only recently has experimental evidence been obtained to support its existence. This review highlights the historical studies of aza-oxyallylic cations and their recent development as intermediates for the synthesis of heterocycles and polyheterocyclic scaffolds.     

Cycloaddition of keteniminium with terminal alkynes toward cyclobuteniminium and their use in Diels–Alder reactions

An efficient access to cyclobutanone derivatives has been developed via a ‘one-pot’ [2+2]/[4+2] sequence involving keteniminium and cyclobuteniminium salts as key intermediates. A broad range of novel cyclobuteniminium salts have been prepared via [2+2] cycloaddition of keteniminium salts and alkynes. The resulting [2+2] adducts were then further transformed by Diels–Alder reaction with various dienes to afford cyclobutanone derivatives in good yields. A density functional theory (DFT) based computational study has been performed to obtain insight into the nature of the cycloaddition reactions and to investigate the difference in reactivity of cyclobuteniminium salts. Finally, the usefulness of cyclobutanone derivatives has been demonstrated by ring expansion reactions affording lactone, lactame, and cyclopentanone derivatives.     

Synthesis of Amido‐linked Oxazolyl/Thiazolyl/Imidazolyl Pyrazoles and Isoxazoles

The amido‐linked oxazolyl/thiazolyl/imidazolyl pyrazoles and isoxazoles were prepared from the synthetic intermediates oxazolyl/thiazolyl/imidazolyl acrylamides adpoting1,3‐dipolar cycloaddition of nitrile imines and nitrile oxides.     

A convenient synthesis of 5-(1,2,4-oxadiazol-5-yl)pyrimidine-2,4(1H,3H)-diones

The synthesis of 5-heteroaryl-substituted uracil derivatives is presented. The 1,3-dipolar cycloaddition reaction was applied for the construction of a heterocyclic ring. The nitrile oxides were obtained from the appropriate 4-substituted benzaldoximes using N-chlorosuccinimide (NCS) under basic conditions. [2+3] Cycloaddition of nitrile oxides with 5-cyanouracil as a dipolarophile gave the corresponding 5-(3-substituited-1,2,4-oxadiazol-5-yl)uracils in satisfactory yields under mild conditions. 5-Substituted uracils having an additional heterocyclic ring were obtained as a result of the [2+3] cycloaddition of 5-cyanouracil to nitrile oxides generated from thiophene-2-carbaldehyde and 5-formyluracil derivatives.     

Cycloaddition of Nitrile Oxides to Graphene: a Theoretical and Experimental Approach

Density functional theory (DFT) studies of the interaction between graphene sheets and nitrile oxides have proved the feasibility of the reaction through 1,3-dipolar cycloaddition. The viability of the approach has been also confirmed experimentally through the cycloaddition of few-layer exfoliated graphene and nitrile oxides containing functional organic groups with different electronic nature. The cycloaddition reaction has been successfully achieved in one-pot from the corresponding oximes under microwave (MW) irradiation. The successful formation of the isoxazoline ring has been confirmed by Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS).     

1,3‐dipolar cycloaddition reactions of nitrile oxides to prop‐1‐ene‐1,3‐sultone

The reaction of prop‐1‐ene‐1,3‐sultone 1 with a variety of nitrile oxides 3 afforded novel [3+2] cycloaddition products 4 in good yield. The cycloaddition reaction achieved excellent regioselectivity.     

Regioselective Cycloadditions of Phosphonyl Nitrile Oxides with Vinylphosphonate and Phosphaalkyne

1,3-Dipolar cycloaddition reactions are important synthetic manipulations allowing the construction of five-membered heterocycles. In this article, we report the cycloaddition of phosphonyl nitrile oxides with vinylphosphonate and phosphaalkyne to form the unexpected 2:1 cycloaddition product with excellent levels of regiocontrol product. The structures of title compounds were confirmed by ¹H NMR, ³¹P NMR, MS, and IR. The mechanism of the cycloaddition was explored using the density functional theory (DFT) method.     

Syntheses and degradations of fluorinated heterocyclics. IV. Imidoylamidoximes, 1,2,4-oxadiazole precursors

Perfluoroalkylether amidoximes free from amide-contamination were prepared from imidate esters. The amidoximes were stable at 110°C; at ～170°C partial decomposition to 1,2,4-oxadiazoles, admixed with other compounds, took place. Interactions between nitriles and amidoximes at 50°C resulted in the formation of imidoylamidoximes; these dissociated readily into their constituents when subjected to higher temperatures. At 70°C and above, in the presence of excess nitrile or other ammonia acceptors, the imidoylamidoximes afforded high yields of the corresponding 1,2,4- oxadiazoles.     

Asymmetric Cycloaddition: An Efficient Synthesis of Enantiopure Isoxazolines Substituted with Carbohydrate Analogues

A simple and convenient method for the synthesis of heterocycles substituted with carbohydrate analogs is described. The chiral optically pure five‐membered glycoconjugates containing the isoxazoline unit were obtained by an aromatic nitrile oxides cycloaddition with 1‐phenyl‐1,2‐dihydro‐pyridazine‐3,6‐dionyl N‐glycoside derivatives.     

Synthesis and nucleophilic substitutions of 3-alkyl-5-chloroisoxazoles

A 3-alkyl-5-chloroisoxazole synthesis is described based on the cycloaddition of nitrile oxides to 1,1-dichloroethylene, an inexpensive dipolarophile. Substitution of the chloride in these adducts by various nucleophiles is also described.     

Synthesis of 2-acylcyclohexane-1,3-diones through tetrahydrobenzisoxalones

A new method was developed for the synthesis of 2-acylcyclohexane-1,3-diones from the adducts of 1,3-dipolar cycloaddition of nitrile oxides to cyclohexenones. The method is examined in the case of the preparation of 2-acetyl-,2-enanthoyl-, and 2-benzoyldimedone.     

Isoxazoles from 1,1-Disubstituted Bromoalkenes

The regioselective synthesis of 3,5-disubstituted isoxazoles was achieved through the 1,3-dipolar cycloaddition of nitrile oxides with 1,1-disubstituted bromoalkenes. The substituted bromoalkenes function as alkyne synthons which were used to construct 5,5-disubstituted bromoisoxazoline intermediates that aromatize to the analogous isoxazoles through the loss of HBr.     

Generation and trapping reaction of an efficient 1,2-dehydrocarborane precursor, phenyl[o-(trimethylsilyl)carboranyl]iodonium acetate

An efficient 1,2-dehydrocarborane precursor, phenyl[o-(trimethylsilyl)carboranyl]iodonium acetate, was readily prepared by reaction of [o-(trimethylsilyl)carboranyl]lithium and IPh(OAc)2. The facile 2+4 cycloaddition of with dienes such as anthracene, naphthalene, norborna-2,5-diene and 2,5-dimethylfuran gave high yields of the 1,2-dehydrocarborane adducts in the presence of a desilylating agent. The reaction of with a cyclic alkene and strained cycloalkynes afforded the adducts formed by the ene reaction and the 2+2 cycloaddition reaction. The reaction of with a bicyclopalladacycle yielded the cyclization product. The structures of compounds and were determined by single-crystal X-ray crystallography.