Treatment of 2-propylideneimino guanidinium acetate with lead tetraacetate, in methylene chloride containing solid sodium carbonate, afforded the previously unknown 3,3-dimethyl-5-imino-Δ1-1,2,4-triazoline. Similarly, N,N′-diphenyl-N″-(2-propylideneimino)guanidinium acetate afforded Z-4-phenyl-5-phenylimino-Δ1-1,2,4-triazoline as the major oxidation product and the corresponding E isomer as a minor product. Stereochemistry was established spectrophotometrically and also by isomerizing the minor (E) isomer to the major (Z) isomer.

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2,5-Dihydro-1,3,4-oxadiazoles with heteroatom substituents at C-2 (also known as corresponding Delta(3)-1,3,4-oxadiazolines) are very useful materials for the thermal generation of acetoxy(alkoxy)-, dialkoxy-, alkoxy(aryloxy)-, diaryloxy-, alkoxy(alkylthio)-, bis(alkylthio)- and alkoxy(amino)-carbenes. Such carbenes are relatively nucleophilic and react with a variety of electrophilic functional groups. This Account reviews our work to prepare 2,5-dihydro-1,3,4-oxadiazoles and apply them to the synthesis of other target molecules. Carbenes bearing alkoxy substituents at the carbene carbon can be looked upon as acetals of carbon monoxide. Their reactions with electron-deficient alkenes or alkynes can afford acetals of cyclopropanones or cyclopropenones. Although such products may be formed by concerted cycloaddition, initial formation of one bond to produce zwitterions is likely in some cases. In addition, the reactions of these molecules with carbonyl compounds could involve acetals of alpha-lactones as intermediates. Although we have isolated some acetals of cyclopropanones, we have not isolated the other intermediates. However, some of the products we observe probably resulted from these intermediates. For example, dimethoxycarbene reacts with maleic anhydrides to generate six-membered rings by apparent carbonyl addition followed by an acyloxy group transfer. Similarly, dimethoxycarbene reacts with thiocarbonyl compounds, such as xanthates, by apparent carbonyl addition and transfer of the alkylthiyl group to the erstwhile carbene carbon. Reaction of ROC:(OR)' with an alcohol R''OH or a phenol should generate chiral (racemic) orthoformates. Similarly, reaction of alkoxy(alkylthiyl) carbenes with alcohols could generate chiral (racemic) dialkyl thiyl orthoformates. 2,5-Dihydro-1,3,4-oxadiazoles are particularly useful for synthetic applications because they are easily prepared and reasonably stable, thermal sources of bis(heteroatom)carbenes. Such carbenes react with a variety of electrophilic functional groups, often with rearrangement of initial products. Those products, many of them new, could be used as starting materials toward other synthetic targets. Isolation of products from the reaction is relatively simple because the coproducts of thermolysis of the oxadiazoles are primarily N(2) and a ketone, such as acetone. Thus, 2,5-dihydro-1,3,4-oxadiazoles should be part of every synthesis chemist's toolbox.

Synthesis of a bicyclic 2,2-dioxa oxadiazoline (6,7-diaza-1-methoxy-5-methyl-2,8-dioxabicyclo[3.2.1]oct-6-ene) is reported. Its thermolysis at 27 degrees C is about 200 times as fast as the thermolysis of a monocyclic oxadiazoline model system. Presumably, a cyclic dioxa carbonyl ylide is formed initially and the ylide then undergoes a bond scission to afford either a dioxacarbene or a dialkylcarbene or it cyclizes to an oxirane. A small fraction of a dialkylcarbene was trapped as the product of addition to dimethyl acetylenedicarboxylate (DMAD). Computations of the barriers to the loss of N-2 from the oxadiazolines and to the formation of the carbenes from the carbonyl ylide resulting from thermolysis of the bicyclic oxadiazoline are compared to corresponding barriers for a similar monocyclic oxadiazoline. The rate acceleration is accounted for in terms of geometric factors. The complex products from the decomposition of the bicyclic oxadiazoline were not studied. Copyright (C) 2007 John Wiley & Sons, Ltd.

2,2-Dimethoxy-3,3-dicyanospiro[cyclopropane-1,9'-[9H]fluorene] reacted fast with methanol to afford 9-trimethoxymethyl-9-dicyanomethyl-9H-fluorene. Reaction with benzaldehydes also gave products of cyclopropane ring opening. Strong electron-donor p-substituents or a strong attractor enhanced the rate. Ring opening of the cyclopropane to a zwitterion that recloses or reacts with an aryl aldehyde, to form either a CO or a CC bond first, can explain the result. The former mode of closure is sensitive to p-substituents because they are directly conjugated to the positive charge at the benzylic carbon of the former aldehyde. The latter mode is sensitive to the ground-state electrophilicity of the carbonyl carbon of the former aldehyde. Thus, reaction of the cyclopropane with p-substituted aldehydes is accelerated by either electron-donor or -acceptor substituents. [reaction: see text].

Dimethoxycarbene, in 2-fold or larger excess, reacts with dimethyl 2,3-dicyanomaleate and fumarate to afford an unstable dihydrofuran 1:1 adduct that was shown to react further with the carbene to afford a 2:1 adduct reported previously. In an astonishing process, the dihydrofuran reacts with water to afford a mixture of (d,l and meso) dimethyl 2,3-dicyanosuccinates in which both hydrogen atoms of water were used to hydrogenate a CC bond.

The reactions of dimethoxycarbene (DMC: 2), which was generated in situ by thermal decomposition of 2.5-dihydro-2,2-dimethoxy-5,5-dimethyl-1,3,4-oxadiazole (1), with N-tosylated imines of xanthone and 23 :6,7-dibenzosuberenone. 3a and 3d, respectively, led to different adducts with rearranged skeletons. In the case of 3a, the 1:1 adduct 5 as well as the 2: 1 adduct 6 were obtained (Scheme 2). The formation of both products can be explained by a migration of a MeO group of the DMC fragment in a zwitterionic intermediate. On the other hand, migration of a Me group of DMC is necessary for the formation of the two 1:1 adducts 13 and 14 of 2 and 3d (Scheme 5). The structures of all products have been established by X-ray crystallography.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Oxidation of the methoxycarbonylhydrazone of p-methoxyacetophenone affords both the cis- and trans-2-acetoxy-2-methoxy-5-(p-methoxyphenyl)-5-methyl-Δ3-1,3,4-oxadiazolines (also known as corresponding 2,5-dihydro-1,3,4-oxadiazoles) as well as methyl 1-acetoxy-1-(p-methoxyphenylethyl)diazenecarboxylate. The three isomers were separated and identified by spectroscopic means. Methyl 1-acetoxy-1-(p-methoxyphenylethyl)diazenecarboxylate is the major product from oxidation in dichloromethane. Oxidation in acetic acid did not afford the oxadiazolines but gave the diazenecarboxylate and, in addition, 1-(p-methoxyphenyl)ethyl acetate. Attempts to isomerize the diazenecar boxylate to the oxadiazolines by acid catalysis were not successful. Thermolysis of the oxadiazolines at 50.4 °C occurred with approximately the same rate constant (ca. 3.6 × 10–5 s–1) to afford acetoxy(methoxy)carbene, which rearranges to methyl pyruvate by acetyl transfer. The carbene, which reacts with relatively unhindered isocyanates to transfer the methoxy carbonyl group to carbon and the acetyl group to nitrogen, can be considered an acyl anion equivalent in that reaction.Key words: acetoxy(methoxy)carbene, diazene, oxadiazoline, isocyanate, (acetylamino)oxoacetate.

Gas-phase pyrolysis of 2-methoxy-2-methylsulfanyl-5,5-dimethyl-2,5-dihydro[1,3,4]oxadiazole (1) (also known as 2-methoxy-5,5-dimethyl-2-methylthio-2,5-dihydro[1,3,4]oxadiazole and 2-methoxy-2-methylthio-5,5-dimethyl-Δ3-l,3,4-oxadiazoline) in the source of an UV photoelectron spectrometer, by means of a CW CO2 laser as directed heat source, gave a photoelectron (PE) spectrum that included ionization bands belonging to acetone and methoxy(methylthio)carbene (3). Photoelectron spectra of authentic samples of (E)-1,2-dimethoxy-1,2-dimethyl thioethene (4), (Z)-1,2-dimethoxy-1,2-dimethylthioethene (5), S-methyl thioethanoate (6), and O-methyl ethanethioate (7), which can be derived by dimerization and rearrangement of the carbene, established that these compounds are not present in the pyrolysate. DFT calculations at the B3PW91/6-31+G(d,p) level and simulation of PE spectra at the B3LYP/6-31+G(d,p) level were instrumental in the interpretation of the experimental results. From the available experimental and calculated data, 3 is formed in a Sickle conformation upon pyrolysis of 1. Transition states for the rearrangement of 3 were examined with QTAIM. Key words: 2-methoxy-5,5-dimethyl-2-methylthio-2,5-dihydro[1,3,4]oxadiazole, pyrolysis, He(I) photoelectron spectroscopy, methoxy(methylthio)carbene, DFT calculations, QTAIM.

[reaction: see text] At 50 degrees C, dimethyl dicyanofumarate and maleate react with 2 equiv of dimethoxycarbene to generate the products shown.

Unlike electrophilic carbenes, which react at sulfur to produce thiocarbonyl ylide intermediates, dimethoxycarbene (DMC), generated by thermolysis of an oxadiazoline at 110 degreesC in benzene in a sealed tube, reacts at carbon, possibly to generate a zwitterionic intermediate, or at both carbon and sulfur in a concerted process that generates a thiirane. In case of the strained 2,2,4,4-tetramethylcyclobutane-1,3-dithione (2), an assumed zwitterion undergoes ring expansion. In analogous reactions, unstrained thiones afford thiiranes, possibly by ring closure of the postulated intermediates or by concerted addition. Desulfurization of thiiranes, which occurs spontaneously in some instances, results in the formation of ketene acetals, many of which hydrolyze during workup. O-Alkyl thioesters and xanthates react to afford products via insertion of the DMC into C-sp2-O or C-sp2-S bonds, respectively. Copyright (C) 2004 John Wiley Sons, Ltd.

Dimethoxycarbene (DMC), generated by thermolysis of 2,2-dimethoxy-5,5-dimethyl–Δ3-1,3,4-oxadiazoline at 110 °C, in benzene in a sealed tube, reacted with most xanthates by formal insertion of the carbene into the S=C‒SR single bond. The reaction course is probably attack of the carbene at carbon of the C= S function, concomitant with (or followed by) migration of the SR group. The products, all new, are mixed orthoesters (two methoxy and one SR at the same carbon), a functional group that has been reported for one case only. In the case where the R group was CO2Me, the reaction became complicated, probably from initial attack at the carbonyl group.

Allyloxy(methoxy)carbene, with and without deuterium in the α-position of the allyloxy group, was generated in benzene at 50 and at 110°C. At the higher temperature, the carbene fragmented to allyl and methoxycarbonyl radicals that subsequently coupled. At the lower temperature, most of the carbene dimerised. The structure of the major product and the distribution of deuterium indicated that the dimer underwent Claisen rearrangement at 50°C to methyl 2-allyloxy-2-methoxy-4-pentenoate. Facile rearrangement of the dimer was supported by the results of a computation which placed the barrier at about 18kcalmol−1.

Thermolysis of 2-acetoxy-2-methoxy-5,5-dimethyl-Delta(3)- 1,3,4-oxadiazoline affords acetoxy(methoxy)carbene. Thermal rearrangement of acetoxy(methoxy)carbene to methyl pyruvate is a concerted 1,2-migration, avoiding a potential radical-pair mechanism. Copyright (c) 2005 John Wiley & Sons, Ltd.

Thermolysis of 2-acetoxy-5,5-dimethyl-2-methylthio-Δ3-1,3,4-oxadiazoline in benzene at 110 °C afforded S-methyl 2-oxopropanethioate (S-methyl thiopyruvate) from 1,2-acyl migration in acetoxy(methylthio)carbene, as well as S,S-dimethyl 2-acetoxy-2-methylpropanebis(thioate) and S-methyl 2-acetoxy-2-(methylthio)butanethioate. The latter two, both composed of two carbene units, are derived from reaction of the first product with the carbene.Key words: acetoxy(methylthio)carbene, carbene, S-methyl thiopyruvate, rearrangement.

Three [3 + 2] cycloreversions of 2-acetoxy-2-methoxy-5,5-dimethyl-Delta(3)-1,3,4-oxadiazolines were examined by computation at the density functional level of theory. The lowest activation energies are those for cycloreversion to 2-diazopropane and acetic methylcarbonic anhydride and for cycloreversion to N(2) and a carbonyl ylide. Those are the reactions that are observed experimentally. A third cycloreversion, to acetoxy(methoxy)diazomethane and acetone, has a much larger barrier. The carbonyl ylide is a real intermediate, but it fragments easily to acetone and acetoxy(methoxy)carbene. The lifetime of the ylide may be so short, in some cases, as to blur the distinction between a two-step cycloreversion of the oxadiazoline and a concerted process that generates three fragments in one step.

Ten new oxadiazoline sources of methoxy(oximino)carbenes were synthesized by exchanging the acetoxy group of 2-acetoxy-2-methoxy-Δ3-1,3,4-oxadiazoline with an oximino group. The new compounds were characterized by means of spectroscopy and the formation of carbenes upon thermolysis of a few was demonstrated by means of interception with tert-butyl alcohol. The carbenes fragmented to form methoxycarbonyl and iminyl radicals.Key words: 2,2-dioxyoxadiazoline, methoxy(oximino)carbene, oxadiazole, radical pair, rearrangement.