Reaction of electron deficient NN bonds with acyloxyketenes and mesoionic 1,3-dioxolium-4-olates: fast equilibrium between acyloxyketenes and mesoionic 1,3-dioxolium-4-olates

Reaction of azodicarboxylates with acyloxyketenes arising from dehydrochlorination of acyloxyphenylacetyl chlorides was carried out to give triacylamidine derivatives in good yields. The same triacylamidine derivatives were also obtained in good yields from the reaction with mesoionic 1,3-dioxolium-4-olates generated by Rh₂(OAc)₄-catalyzed decomposition of phenyldiazoacetic anhydride derivatives. Formation of the same compounds from different starting materials is explained by 1,3-dipolar addition between electron deficient NN bonds and mesoionic 1,3-dioxolium-4-olates, indicating fast equilibrium between acyloxyketenes and mesoionic 1,3-dioxolium-4-olates.     

Reaction of electron-deficient N=N, N=O double bonds, singlet oxygen, and CC triple bonds with acyloxyketenes or mesoionic 1,3-dioxolium-4-olates: generation of unstable mesoionic 1,3-dioxolium-4-olates from acyloxyketenes

Reactions of azodicarboxylates and nitrosobenzene derivatives with acyloxyketenes generated from dehydrochlorination of alpha-acyloxyarylacetyl chlorides were carried out to give triacylbenzamidine and N-arylimide derivatives, respectively, in good yields. The same compounds were obtained from the reaction with mesoionic 1,3-dioxolium-4-olates generated by Rh2(OAc)4-catalyzed decomposition of aryldiazoacetic anhydride derivatives. Formation of the same compounds from the different starting materials indicates that their reactions involve the same intermediates. The formation of triacylbenzamidine and N-arylimide derivatives is explained by 1,3-dipolar cycloaddition between electron-deficient N=N or N=O bonds and mesoionic 1,3-dioxolium-4-olates following by decarboxylation, ring opening of the resultant carbonyl ylides, and subsequent Mumm rearrangement of the corresponding imidates. The reaction with singlet oxygen composed of more electronegative atoms than N=N and N=O bonds also gave products arising from the singlet oxygen adducts with 1,3-dioxolium-4-olates. The generation of less stable mesoionic 1,3-dioxolium-4-olates from acyloxyketenes was also confirmed by isolation of furandicarboxylates on generation of acyloxyketenes from alpha-acyloxyarylacetyl chlorides in the presence of reactive dipolarophile dimethyl acetylenedicarboxylate.     

Fast ring opening of unstable mesoionic 1,3-dioxolylium-4-olates to acyloxyketenes: formation of [2+2] cycloadducts of acyloxyketene with several ketenophiles

Fast ring opening of mesoionic 1,3-dioxolylium-4-olate 5, generated by Rh₂(OAc)₄-catalyzed decomposition of a phenyldiazoacetic anhydride 6, to an acyloxyketene 10 was demonstrated by trapping the ketene 10. Rh₂(OAc)₄-catalyzed decomposition of p-nitrophenyldiazoacetic p-chlorobenzoic anhydride 6a in the presence of ketenophiles such as dihydrofuran, carbodiimides, and imines did not give 1,3-dipolar cycloadducts with the 1,3-dioxolylium-4-olates 5a, but their [2+2]-cycloadducts with the acyloxyketene 10a. PM3 calculation of heats of formation of a 1,3-dioxolylium-4-olate 5 and an acyloxyketene 10 indicates that the acyloxyketene 10 is 9 kcal/mol more stable than the 1,3-dioxolylium-4-olates 5.     

Convenient synthesis of alpha-trifluoromethylated acyloins from alpha-hydroxy or alpha-amino acids

Alpha-trifluoromethylated acyloins (2 and 6) have been prepared from alpha-hydroxy acids (1), N-acylprolines (5) or N-acyl-N-alkyl alpha-amino acids (8) by novel transformation reactions with trifluoroacetic anhydride (TFAA) in the presence of pyridine. The former reaction of 1 could proceed through mesoionic 1,3-dioxolium-4-olates, whereas the latter two reactions of alpha-amino acids (5 and 8) could involve mesoionic 1,3-oxazolium-5-olates. The reaction of 1 with TFAA shows more potential for practical applications because of the ready availability of the starting materials and ease of manipulation.     

Intermolecular 1,5-dipolar cycloaddition reaction of tungsten-containing vinylazomethine ylides leading to seven-membered heterocycles

[STRUCTURE: SEE TEXT] Intermolecular 1,5-dipolar cycloaddition reaction of tungsten-containing vinylazomethine ylide, generated from o-(alk-3-en-1-ynyl)phenylbenzaldimines and tungsten carbonyl complex, with ketene acetals proceeds efficiently to give azepino[1,2-a]indole derivatives in good yield. Formation of [5+2] or [3+2] cycloadducts can be controlled by an appropriate choice of dipolarophile.     

Convenient synthesis of ferrocenyl β-C-glycosydic spiropyrrolidines and pyrrolizidines through 1,3-dipolar cycloaddition reaction

An expedient method for the synthesis of ferrocene grafted β-C-glycosydic spiroheterocycles is reported through 1,3-dipolar cycloaddition reaction (1,3-DC reaction). The novel C-glycosyl dipolarophiles derived from d-glucose, d-mannose, and d-ribose underwent neat [3+2] cycloaddition reaction with the azomethine ylides generated from 1,2-diketones and secondary amino acids to give the corresponding β-C-glycosidic heterocycles in good yields. The electrochemical behavior of the cycloadducts is also described.     

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.     

Novel quinone-fused corroles

Gallium(III)(pyridine) complex of 5,10,15-tris(pentafluorophenyl)corrole-3-carbaldehyde was used as a precursor of an azomethine ylide, which was trapped in 1,3-dipolar cycloaddition reactions with quinones. Besides the expected dehydrogenated 1,3-dipolar cycloadducts, novel quinone-fused corrole derivatives were also obtained in moderate yields.     

Substrate-controlled and site-selective [3+2] cycloadditions of N-heterocyclic carbene derived ambident dipoles

2-aryl thiocarbamoyl benzimidazolium and imidazolinium inner salts derived from benzimidazole and imidazoline carbenes are unique ambident C-C-S and C-C-N 1,3-dipolar systems, which undergo highly efficient and site-selective cycloaddition reactions with dimethyl acetylenedicarboxylate or dibenzoylacetylene to furnish spiro(imidazole-2,3'-thiophene) derivatives in excellent yields. When treated with ethyl propiolate, methyl acrylate or acrylonitrile, spiro(imidazole-2,3'-pyrrole) derivatives were formed in good yields. Theoretical studies revealed an asynchronous concerted mechanism for both the C-C-S and C-C-N 1,3-dipolar cycloaddition reactions. The site selectivity in the [3+2] cycloaddition reaction of ambident 1,3-dipoles was predictably regulated by both the electronic and steric effects of dipolarophiles.     

Transition states for the dimerization of 1,3-cyclohexadiene: a DFT, CASPT2, and CBS-QB3 quantum mechanical investigation

Quantum mechanical calculations using restricted and unrestricted B3LYP density functional theory, CASPT2, and CBS-QB3 methods for the dimerization of 1,3-cyclohexadiene (1) reveal several highly competitive concerted and stepwise reaction pathways leading to [4 + 2] and [2 + 2] cycloadducts, as well as a novel [6 + 4] ene product. The transition state for endo-[4 + 2] cycloaddition (endo-2TS, DeltaH(double dagger)(B3LYP(0K)) = 28.7 kcal/mol and DeltaH(double dagger)(CBS-QB3(0K)) = 19.0 kcal/mol) is not bis-pericyclic, leading to nondegenerate primary and secondary orbital interactions. However, the C(s) symmetric second-order saddle point on the B3LYP energy surface is only 0.3 kcal/mol above endo-2TS. The activation enthalpy for the concerted exo-[4 + 2] cycloaddition (exo-2TS, DeltaH(double dagger)(B3LYP(0K)) = 30.1 kcal/mol and DeltaH(double dagger)(CBS-QB3(0K)) = 21.1 kcal/mol) is 1.4 kcal/mol higher than that of the endo transition state. Stepwise pathways involving diallyl radicals are formed via two different C-C forming transition states (rac-5TS and meso-5TS) and are predicted to be competitive with the concerted cycloaddition. Transition states were located for cyclization from intermediate rac-5 leading to the endo-[4 + 2] (endo-2) and exo-[2 + 2] (anti-3) cycloadducts. Only the endo-[2 + 2] (syn-3) transition state was located for cyclization of intermediate meso-5. The novel [6 + 4] "concerted" ene transition state (threo-4TS, DeltaH(double dagger)(UB3LYP(0K)) = 28.3 kcal/mol) is found to be unstable with respect to an unrestricted calculation. This diradicaloid transition state closely resembles the cyclohexadiallyl radical rather than the linked cyclohexadienyl radical. Several [3,3] sigmatropic rearrangement transition states were also located and have activation enthalpies between 27 and 31 kcal/mol.     

Heteropolyacid–silica mediated [3+2] cycloaddition of azomethine ylides—a facile multicomponent one-pot synthesis of novel dispiroheterocycles

An efficient synthesis of dispiroindenoquinoxaline pyrrolizidine derivatives has been expediently accomplished by a one-pot four component 1,3-dipolar cycloaddition reaction. High regioselectivity was achieved using heteropolyacid H₄[Si(W₃O₁₀)₃]–silica as a catalyst. X-ray diffraction studies of one of the cycloadducts proved the structure and regiochemistry of the cycloadduct.     

2 + 4] and [4 + 2] cycloadditions of o-thioquinones with 1,3-dienes: a computational study

Cycloadditions of o-thioquinones (o-TQs) with 1,3-dienes could proceed via either a [2 + 4] or a [4 + 2] mechanism. Under kinetic control and with acyclic dienes the reaction affords the spiro cycloadducts 5deriving from the [2 + 4] path as the main products. Under thermodynamic control, or with cyclic dienes, the o-TQs behave as heterodienes to give the benzoxathiin derivatives 4, in most cases with complete regioselectivity. In the present computational study, DFT calculations were performed in order to achieve a deep understanding of both [2 + 4] and [4 + 2] paths. The reactions of three o-TQs with six 1,3-dienes were thoroughly investigated at the B3LYP/TZVP//B3LYP6-31G level, and the two reaction mechanisms were then compared, evidencing that [2 + 4] cycloadditions are kinetically favored, strongly asynchronous, or even unconcerted, while [4 + 2] reactions are thermodynamically favored, quite asynchronous, but undoubtedly concerted. Moreover, the observed regioselectivity was rationalized by mean of the FMO theory and by comparison of the activation energies for different pathways.     

New thiopyran-4-spiro-2′-(1,3-dithiolane):Formation mechanism and crystal structure

Ethylene trithiocarbonate reacted with dimethyl acetylenedicarboxylate to furnish tetramethyl thiopyran-4-spiro-2'-(1,3- dithiolane)-2,3,5,6-tetracarboxylate,a new thiopyran-4-spiro-2'-(1,3-dithiolane) heterocyclic compound,as the minor product together with the major product dimethyl 2-thioxo-1,3-dithiole-4,5-dicarboxylate.The new heterocycle was probably formed through a[2 + 2]cycloaddition between ethylene trithiocarbonate and dimethyl acetylenedicarboxylate followed by a 1,3-dipolar cycloaddition or[...     

Synthesis of New Spiro[1,4,2-dioxazole-5,3′-indolin]-2′-one by 1,3-Dipolar Cycloaddition

Novel spiro[1,4,2-dioxazole-5,3′-indolin]-2′-one derivatives were synthesized by 1,3-dipolar cycloaddition reactions of the isatin derivative with aryl nitrile oxide. The cycloadducts were characterized by spectral data including ¹H NMR, ¹³C NMR, infrared, mass spectra, and elementary analysis.     

4-Isoxazolines and pyrroles from allenoates

The synthesis of 4-isoxazolines via 1,3-dipolar cycloaddition of nitrones generated from allenoates and the subsequent thermal rearrangement to pyrroles is reported. The selection of the reaction conditions allowed the isolation of the initial 1,3-dipolar cycloadducts, the 4-isoxazolines, or the pyrrole derivatives. The isomerization of the parent system (4-isoxazoline) was examined by carrying out quantum chemical calculations and corroborated the favourability of the 4-isoxazoline rearrangement to five-membered heterocycles via 2-acylaziridine intermediates.     

PtCl2-Promoted cyclopropane opening in [4+2+2] homo Diels-Alder cycloadducts

A new and readily available catalytic system has been developed to open the cyclopropane ring in [4+2+2] homo Diels-Alder cycloadducts formed by reaction of norbornadienes and 1,3-butadiene. The cobalt-mediated homo Diels-Alder reaction followed by this PtCl₂-promoted isomerization is a key step in the efficient route to bicyclo[5.3.0]decanes, core of numerous natural products.     

Catalytic enantioselective 1,3-dipolar cycloaddition of azomethine ylides with vinyl sulfones

[reaction: see text] A general protocol for the enantioselective catalytic 1,3-dipolar cycloaddition of azomethine ylides with aryl vinyl sulfones is described. Nearly complete exo selectivity and enantioselectivities up to 85% ee are attained with Cu(CH(3)CN)(4)ClO(4)/Taniaphos as the catalyst system. The resulting enantioenriched 3-sulfonyl cycloadducts are versatile intermediates in the synthesis of 2,5-disubstituted pyrrolidines.     

Expedient Approach for the Synthesis of Trispiropyrrolidine Bisoxindoles Through 1,3-Dipolar Cycloaddition Reactions

A series of trispiropyrrolidine bisoxindoles has been achieved via a three-component 1,3-dipolar cycloaddition reaction of 3-aryl-5-arylmethylenespiro[indole-3′,2-[1,3]thiazolane]-2′(1H),4-dione, isatin, and sarcosine in refluxing toluene, which produced the corresponding cycloadducts in good yields (79–88%). Their structures were determined by infrared, ¹H and ¹³C NMR, elementary analysis, and single-crystal x-ray diffraction analysis, and the cycloaddtion reaction was found to be highly regio- and stereoselective.     

1,3-dipolar cycloaddition of 2-dialkylaminothioisomünchnones with aliphatic aldehydes: synthesis of beta-lactams and thiiranes,structure elucidation,and rationale for chemoselective fragmentation of cycloadducts

A series of highly funtionalized beta-lactams and thiiranes can be generated on treatment of 1,3-thiazolium-4-olates (thioisomünchnones) with aliphatic aldehydes. Although in some cases a variety of products have been obtained, the present paper now provides a mechanistic rationale to explain the product distribution based on stereoelectronic effects. Thus, ring fragmentation of the initial [3+2] cycloadduct is essentially dictated by the electronic character of the aryl substituent on the nitrogen atom of the parent thioisomünchnone. However, further evolution of such cycloadducts into beta-lactams or thiiranes is governed by steric effects to a large extent. Evidence for such interactions has been obtained by computing PM3-optimized diastereomeric transition structures in the reaction of a thioisomünchnone with a chiral aliphatic aldehyde.     

Novel [4 + 2]-cycloaddition of 1-phenyl-1-benzothiophenium salts with dienes. Experimental evidence for a lack of aromaticity in the thiophene ring

The [4 + 2]-cycloaddition reaction of 1-phenyl-1-benzothiophenium triflates has been conducted for the first time. [4 + 2]-Cycloaddition with dienes such as cyclopentadiene and 1,3-diphenylisobenzofuran occurs successfully to give cycloadducts. This result indicates that the C=C bond of the thiophene ring acts as a 2pi electron component in the cycloaddition reaction. Cycloadducts were formed in high yields with high stereoselectivity. However, the cycloaddition with other less reactive dienes such as 2,3-dimethyl-1,3-butadiene did not take place. The structure and stereochemistry of cycloadduct 2a were analyzed by NMR techniques. Furthermore, reaction of the cycloadducts with sodium methoxide in methanol gave the ring-opened products in high yields.