Initial Cycloadduct Research Articles

The azomethine ylide strategy for β-lactam synthesis. Azapenams and 1-azacephams

Reaction of the β-lactam-based oxazolidinone 5 with N-sulfonylimines provides the exo and endo azapenams 8 in 22–54% yield. The reactivity of 2H-azirines as 1,3-dipolarophiles towards β-lactam-based azomethine ylides derived from oxazolidinones 5 and 15 has also been evaluated. Azirines 11 and 12a provide cycloadducts 13a,b and 16 respectively, which incorporate the novel 2,6-diazatricyclo[4.2.0.02,4]octan-7-one ring system. These adducts were resistant towards C–N cleavage as the basis of an entry to 1-azacephams (1,5-diazabicyclo[4.2.0]octan-8-ones) 4. The use of the 3-(4-methoxyphenyl)-2H-azirine 19 provides a labile initial cycloadduct, which undergoes in situ ring-cleavage and further reaction to give the 2 ∶ 1 adduct 1-azacepham 22. The initial product is stable when 3-(4-nitrophenyl)-2H-azirine 23 is employed, and cycloadducts 24a and 24b are converted under mild reducing conditions to the 1-azacepham derivatives 25 and 26.

Synthesis of thiadiazole, dithietane, and imine derivatives of the [1,2]dithiolo[1,4]thiazine ring system.

We report the synthesis of some new polysulfur-nitrogen heterocyclics by cycloaddition reactions to the thioketo group of readily available tricyclic 1,2-dithiole-3-thiones. Thus treatment of bis[1,2]dithiolo[1,4]thiazine ketothione 1 with diaryl nitrile imines generated from hydrazonoyl chlorides 2a-g gave [1,3,4]thiadiazolylidenyl[1,2]dithiolo[1,4]thiazines 4a-g in high yield. Compounds 4a-f, bearing the same substituents in both aryl groups, were stable but the analogous 4g,h with a p-nitrophenyl group on carbon gave the bis[1,2]dithiolo[1,4]thiazine dione 9, probably by cycloreversion and hydrolysis during chromatography. Treatment of 1, the bis[1,2]dithiolopyrrole ketothione 13, and dithione 12 with ethoxycarbonyl azide 11 gave imines 12 and 15 and bisimine 16, respectively, by an alternative fragmentation of the initial cycloadduct in which the 1,2-dithiole ring is retained. Reaction of 1 with TosMIC gave the imino-1,3-dithietane 17.

Reactions of Nitromethane on Si(100): First-Principles Predictions

Reactions of nitromethane on Si(100) are investigated using density functional theory. Calculations show that nitromethane should strongly chemisorb to the surface dimer by means of a 1,3-dipolar cycloaddition reaction pathway, with no significant activation barrier. Though the 1,3-dipolar cycloaddition results in a strongly bound product, this initial cycloadduct is metastable with respect to rearrangement products formed through oxygen migrations between lattice silicons. Multiple products are likely to be present on the surface, so that it will not be well ordered. This reaction suggests a new route for attaching organic monolayers to Si(100) and provides a model system for bonding in silicon oxynitride films.

Synthesis of mesomeric betaines containing a pyrrolo- or imidazotriaziniumolate system and their cycloaddition with acetylenic dipolarophiles leading to triazocinone derivatives

A series of 2-substituted mesomeric betaines containing a cyclic azomethine imine unit were synthesized and their cycloaddition with acetylenic dipolarophiles were examined. Unexpectedly the cycloaddition of the betaines with electron-deficient dipolarophiles gave ring-expanding adducts having a triazocinone structure. With electron-rich dipolarophiles such as ynamines, the reactions proceeded more readily leading regioselectively to the same type of triazocinones in almost quantitative yields. In particular in the case of an imidazobetaine and an ynamine the cycloaddition took place at room temperature to afford the initial cycloadducts exclusively and in excellent yields. The isolated tricyclic precursors were found to rearrange quantitatively to the final products on heating to 60°C.

2+3] Cycloadditions of ‘Thiocarbonyl Ylides’ (= (Alkylidenesulfonio)methanides) and diazoalkanes with N,N′‐(thiocarbonyl)diimidazole (= 1,1′‐(carbonothioyl)bis[1H‐imidazole

AbstractHeating of a mixture of N,N′‐(thiocarbonyl)diimidazole (= 1,1′‐(carbonothioyl)bis[1H‐imidazole]; 1) and 2,5‐dihydro‐1,3,4‐thiadiazole 2a or 2b gave the 1,3‐dithiolanes 4a and 4b, respectively, via a regiospecific 1,3‐dipolar cycloaddition of the corresponding ‘thiocarbonyl methanides’ 3a,b onto the CS group of 1 (Schemes 1 and 2). The adamantane derivative 4b was not stable in the presence of 1H‐imidazole and during chromatographic workup. The isolated 1,3‐dithiole 5 is the product of a base‐catalyzed elimination of 1H‐imidazole from the initial cycloadduct 4b. The formation of the S,N‐acetal 6 can be rationalized by a protonation of the ‘thiocarbonyl ylide’ 3b followed by a nucleophilic addition of 1H‐imidazole. With the diazo compounds 8a–e (Scheme 3) 1 underwent a regiospecific 1,3‐dipolar cycloaddition to give the corresponding 2,5‐dihydro‐1,3,4‐thiadiazole derivatives 9, which spontaneously eliminated 1H‐imidazole to yield (1H‐imidazol‐1‐yl)‐1,3,4‐thiadiazoles 10. The structures of 10a and 10d were established by X‐ray crystallography. In the case of diazodiphenylmethane (8f), the initial cycloadduct 9f decomposed via a ‘twofold extrusion’ of N2 and S to give 1,1′‐(2,2‐diphenylethenylidene)bis[1H‐imidazole] (11; Scheme 3).

Competing Pathways in the Azomethine Ylide Route to Indoloquinones: An Improved Procedure for the Generation of a Transient 4-Oxazoline from the Oxazolium Salt

Azomethine ylide generation from the oxazolium salt 22 and PhSiH3/CsF affords complex products derived from the initial cycloadduct 23 via three competing pathways. Colorless intermediates 24−27 have been detected, and their oxidation products 10, 28, and 29 have been identified. Nucleophilic activation of the oxazolium salt 22 is reported using the organic-soluble benzyltrimethylammonium cyanide. This variation affords the unstable cycloadduct 32, which undergoes aromatization via a single pathway involving 24 and 27, and DDQ oxidation gives the indoloquinone 10 in an improved 63% yield. Lower yields using PhSiH3/CsF or NaCN activation methods are attributed to the heterogeneous conditions and interception of the azomethine ylide by unreacted oxazolium salt.

Highly selective 1,3-dipolar cycloadditions of captodative olefins 1-acetylvinyl carboxylates to diverse dipoles

Regioselective 1,3-dipolar cycloadditions of captodative 1-acetylvinyl p-nitrobenzoyloxy ( 1a) with propionitrile oxide, diphenylnitrile imine and diazoalkanes provided the corresponding 5-acetyl- isoxazoles and pyrazoles. Evidence to support the formation of the initial cycloadducts was obtained. The addition of nitrones also proved to be highly regio- and stereoselective.

Hetero-1,3-dipolar cycloadditions of dithiolane-isocyanate imminium methylides: A novel route to 1,3-oxazolidine- and thiazolidine-2-thiones

Dithiolane-isocyanate imminium methylides which are a new type of azomethine methylide-derived 1,3-dipole undergo efficient and regioselective cycloaddition to conjugated carbonyls and thiocarbonyls to yield predominantly 1,3-oxazolidine- and thiazolidine-2-thiones formed from the initial cycloadducts via loss of thiirane.

Cycloaddition Chemistry of 1,3-Thiazolium-4-olate Systems. Reaction with Nitroalkenes and Interpretation of Results Using PM3 Calculations.

1,3-Dipolar cycloaddition of 1,3-thiazolium-4-olates, readily prepared from thioureido derivatives, and trans-beta-nitrostyrene at room temperature in methylene chloride (48 h) resulted in two readily separable diastereomeric racemic 4,5-dihydrothiophenes via transient cycloadducts that underwent rearrangement under these reaction conditions. Using chiral carbohydrate-derived nitroalkenes, two diastereomeric dihydrothiophenes were obtained, showing that regiospecificity and facial selectivity were involved in these cycloadditions. (1)H NMR data and trapping experiments with isolated initial cycloadducts indicated that the cycloadditions were reversible and accounted for observed adduct and final product ratios. Single-crystal X-ray determinations established the structures of critical intermediates and products, and PM3 semiempirical MO calculations provide a rationalization for both the reactivity of the thiazolium-4-olates and the regioselectivity observed in the cycloadditions.

Diels−Alder Reactions of Chiral 1,3-Dienes

Structurally related 1,3-dienes 3a−f attached to a chiral carbon were treated with maleic anhydride under a variety of conditions. The initial Diels−Alder adducts were not isolated as they spontaneously rearranged to the isomeric isoindolones 6 and 7. The rate of the rearrangement was dependent on the relative stereochemistry of the initial cycloadducts. The π-facial selectivity of the Diels−Alder reaction was determined by analyzing reaction mixtures of the isomeric isoindolones by 1H and 13C NMR spectroscopy and HPLC. A gradual increase in the π-facial selectivity was observed when the homoallylic hydroxyl group of the diene was endowed with a larger protecting group or slightly increased by performing the reactions in ether saturated with LiClO4. These effects were rationalized by proposing a model based on 1,3-allylic strain in the transition state for the dienes 3a−f.

Base-induced conversion of 5-aminothiazolium salts into substituted pyrroles and pyrrolines via 1,3-dipolar cycloadditions with electron-deficient alkynes and alkenes

A series of mesoionic thiazoles 2 were generated and converted in situ by treating the 5-aminothiazolium chlorides 1 with several electrophilic dipolarophiles in the presence of DBN or NEt 3. The reactions involved an 1,3-dipolar cycloaddition of the “masked” cyclic azomethine ylides across the olefinic or acetylenic π-bond, yielding unstable N-bridged adducts as the first step. Thus, DMAD and methyl propiolate gave functionalized pyrroles via a subsequent extrusion of isothiocyanate. Dimethyl fumarate, maleate and fumaronitrile afforded a variety of polysubstituted pyrrolines, pyrroles and aminobutadienes through base-catalyzed rearrangements of the primary 1 : 1 cycloadducts, with retention of the elements of isothiocyanate. A similar initial cycloadduct 17 was isolated from N-phenylmaleimide which generally led to the condensed imino thiopyrans 20. Some of the 1,3-dipolar reactional stereoselectivities were deduced from the stereochemistry or distribution of the final products and found to be markedly dependent on the substituent groups present.

Regio- and stereo-selective 1,3-dipolar cycloaddition reactions of ethyl diazoacetate to 3-substituted 2 H-1-benzopyran-2-ones.

The cycloaddition of ethyl diazoacetate to 3-substituted 2 H-1-benzopyran-2-ones, 1, gave the benzopyranol[3,4][2]pyrazolines 11, the benzopyrano[3.4]cyclopropanes 12, the benzopyrano[3,4- c]pyrazole 13 and the ( o-hydroxy)phenyl-pyrazoles 14 as the main products. When the cycloaddition was performed in the presence of silica gel the rate of the reaction increased substantially and the yields of the cyclopropane derivatives 12 were more than doubled. Ethyl diazoacetate adds to benzopyran-3,4-double bond regio- and stereo-selectively giving the endo-form of the initial cycloadduct 15, which being unstable, is then transformed mainly to the above mentioned compounds.

Exploration of the [3 + 2] Cycloaddition Reaction Between Allylstannanes and α,β-Unsaturated Acyliron Complexes

The reaction between allylstannanes and α,β-unsaturated acyliron complexes has been investigated. Contrary to the behavior of other α,β-unsaturated carbonyl compounds, α,β-unsaturated acyliron complexes react with allylstannanes to produce predominately cyclopentane derivatives with a high degree of stereoselectivity. The initial cycloadducts contain acyliron and trialkylstannyl functionalities, which are readily converted to ester and alcohol groups, respectively, with complete retention of stereochemistry. Transition state models involving a synclinal orientation of reactants have been proposed to explain the observed stereochemistry. Studies of cyclization reactions of 5-hexenylstannanes have also been described. 1. Introduction 2. Why Examine the Reaction Between Allylstannanes and α,β-Unsaturated Acyliron Complexes in the First Place? 3. Optimization of the Reaction Between Allyltributyltin and Acryloyldicarbonyl(η-cyclopentadienyl)iron (2). 4. Will Allyltributyltin React with Other α,β-Unsaturated Acyliron Complexes in the Same Manner? 5. Will Acryloyliron Complex 2 React Similarly with Other Allylic Tributylstannanes? 6. Reactions in which Both Cycloaddition Partners Bear Additional Substituents 7. What Do Other Allylmetal Complexes Do? 8. Development of Methods for Conversion of the Metals to Simpler Functional Groups 9. Development of New C-Sn Bond Cleavage Reactions 10. Assignment of Stereochemistry 11. What Is the Mechanism of the Reaction? 12. How Do We Explain the Observed Stereoselectivity? 13. What's So Great About This Model? 14. Why Do α,β-Unsaturated Acyliron Complexes Behave So Differently from Other α,β-Unsaturated Carbonyl Compounds? 15. How Do We Explain Those Cases Where Open-Chain Products Are Obtained? 16. Summary and Outlook

Organic heterocyclothiazenes. Part 16. Reactions of trithiadiazepyne with cyclopentadienones. Some stable norbornadienones

Trithiadiazepyne reacts with 2,5-dimethyl-11a and 2,5-diethyl-3,4-diphenylcyclopentadienone 11b in hot acetonitrile to give the initial Diels–Alder cycloadducts, 12a and 12b, which are remarkably stable norbornadienones. It reacts similarly with 2-methyl-3,4,5-triphenylcyclopentadienone 15 in cold acetonitrile to give the less stable carbonyl-bridged adduct 28. These initial cycloadducts readily lose carbon monoxide when heated to give the aromatic benzotrithiadiazepines, 13 and 29. In the reaction of trithiadiazepyne with phencyclone 8 the decarbonylated product 9 is the first to be isolated. With tetracyclone 2, and with the methyltriphenyl analogue 15 in hot acetonitrile, two molecules of the aryne are involved and more extensive reactions result in formation of the dithiins, 3 and 16, respectively. Stronger heating of the benzotrithiadiazepines induces a molecular arrangement with loss of nitrogen to give benzo-1,2,3-trithioles, 10, 14a,b and 17. A reaction sequence is proposed (Scheme 6) to explain the formation of all of these products.

Synthetic approaches to phorbols via the intramolecular Diels–Alder reaction of furans: influence of the dienophile upon the stereochemical control

A carbotricycle (13) having the same relative stereochemistry as the phorbols at 6 centres has been constructed via stereoselective Intramolecular Diels–Alder reaction of furans (IMDAF) of a precursor (7) possessing a Z-vinylogous ketoester followed by selective epimerisation at C-10 of the initial cycloadduct (11); whereas the corresponding E-isomer (8) or alkyne (3) show no stereoselection in the IMDAF.

1,5-Dihydropyrrol-2-ones from (1,4-diaza-1,3-diene)tricarbonyliron, (DAD)Fe(CO)3, and alkyne. 5. Spectroscopic and x-ray structural characterization of a bicyclo[2.2.1] complex resembling the initial cycloadduct. The C = N-Fe fragment in (DAD)Fe(CO)3 as an isolobal analog of the classical 1,3-dipole azomethine ylide in 1,3-dipolar cycloaddition

1,5-Dihydropyrrol-2-ones from (1,4-diaza-1,3-diene)tricarbonyliron, (DAD)Fe(CO)3, and alkyne. 5. Spectroscopic and x-ray structural characterization of a bicyclo[2.2.1] complex resembling the initial cycloadduct. The C = N-Fe fragment in (DAD)Fe(CO)3 as an isolobal analog of the classical 1,3-dipole azomethine ylide in 1,3-dipolar cycloaddition

1,3-Dipolar cycloadditions of 1-(N-arylidene)amino-1, 2,3-triazoles with diphenylnitrilimine

1-(N-Arylidene)amino-1,2,3-triazoles (1) and (9) react with diphenylnitrilimine (2) to give the corresponding 1,2,3- and 1,2,4-triazoles (3) and (4) as well as 1- and 2-benzohydrazonoyl-1,2,3-triazoles (5), (10) and (6) and (11) respectively. These products are formed assuming an initial cycloadduct, (7), which upon elimination of the triazole ring gives compounds (3) and (4). Further reaction of the triazole system with (2) gives the hydrazone derivatives (5), (6), (10), and (11). The reaction is also studied on the basis of frontier molecular orbitals (FMO) of the reacting species.

XY–ZH systems as potential 1,3-dipoles. Part 6. Metallo-1,3-dipoles. Cycloadditions of divalent metal complexes of glycine and alanine imines to electronegative olefins

Copper(II), zinc(II), and cadmium(II) complexes of imines derived from α-oxo acids and glycine or alanine undergo stereospecific cycloaddition at room temperature to 1,2-disubstituted electronegative olefins in the presence of weak base. Corresponding reactions of lead(II) complexes give insoluble cycloadducts. In contrast, the reactions of the same metallo imines with methyl acrylate, phenyl vinyl sulphone, and acrylonitrile frequently give mixtures of regio- and stereo-isomers. These mixtures are shown to arise by stereoisomerisation of initial cycloadducts formed by a 4π+ 2π concerted cycloaddition of intermediate metallo-1,3-dipoles.

Cycloaddition reactions of 1,4,2-dithiazole-5-thiones

1,4,2-Dithiazole-5-thiones can act either as the 2-atom or the 3-atom component in 2 + 3-cycloadditions. Benzonitrile N-phenylimine, generated in situ by dehydrochlorination of N-phenylbenzohydrazonoyl chloride, reacts at the exocyclic CS double bond forming the thiadiazolethione (17) and the spiro compound (18) by collapse of the initial cycloadduct (19) and further 1,3-dipolar cycloaddition. The corresponding reaction with ethyl azidoformate yields a 5-ethoxycarbonylimino-1,4,2-dithiazole. On treatment with dimethyl acetylenedicarboxylate and ethyl cyanoformate the dithiazolethione itself acts as a 1,3-dipole forming 1,3-dithiole and 1,4,2-dithiazole thiones with expulsion of a nitrile fragment.

1,3-Dipolar cycloaddition of azolium dicyanomethylides

1,3-Dipolar cycloaddition of azolium N-dicyanomethylides, which have an azomethine ylide structure, to acetylenic dipolarophiles affords azolopyridine derivatives. The initial cycloadduct has been isolated for the first time. Using unsymmetrical dipolarophiles, only one of the two possible regioisomers has been obtained. The orientation problem has been approached theoretically by a second-order perturbational treatment, which also gives good results in the case of the reaction of an azomethine imine, 1-ethylbenzotriazolium 3-dicyanomethylide.