Thermolysis diazo compounds

Thermal conversion of diazirines to linear diazo compounds was postulated occasionally and proved by indirect methods. The existence of a diazo compound isomeric to diazirine (197) was proved spectroscopically on short thermolysis in DMSO (76JA6416). An intermediate diazoalkane was trapped by reaction with acetic acid, yielding the ester (198) (77JCS(P2)1214). 

In the case of sodium 2-(diarylmethylene)cyclopentanone tosylhydrazones 3, however, thermolysis gives the 3//-1,2-benzodiazepines 6 in good yield selected examples are shown. It is suggested that steric constraints in the diazo compounds 4 favor the [1,7] ring closure. The reaction proceeds by way of the intermediates 5, which rearrange to the products by a [1,5] shift of hydrogen.115... 

Cyclizations of doubly unsaturated diazo compounds containing a thiophene ring within rather than at the end of the diene system to yield thicnodiazepines have also been reported. Thus, thermolysis of the sodium salt 7 gives the l//-thieno[3,2-r/]-2,3-diazepine 9. The intermediate 8 rearranges to the more stable product 9 by a symmetry allowed [1,5] shift of hydrogen.14,1... 

More recently, Williams has described the one pot synthesis of 2-substituted oxazoles 11 by the thermolysis of triazole amides 9 the reaction does not proceed photo-chemically.<92TL1033> Although the reaction does not involve addition to a nitrile, it is an interesting application of a diazo compound since the proposed zwitterionic intermediate 10 is a resonance form of a diazo imine, so formally the reaction may be thought of as a thermal decomposition of a diazo imine (Scheme 6). 

The triplet state is usually the ground state for non-conjugated structures, but either species can be involved in reactions. The most common method for generating nitrene intermediates, analogous to formation of carbenes from diazo compounds, is by thermolysis or photolysis of azides.246... 

Thermolysis of 58a in butanol affords, together with 17% of 60a (R = C4H9) which evidences the intermediacy of the thiophosphene 59 a, a variety of partly atypical products which seriously impede the desired rearrangement38. Photolysis of 58b in methanol is also found to give only 18 % 1,2-P/C shift to form the heterocumulene 59b, from which the thiophosphinic rater 60b (R = CH3) results 39). As already mentioned in connection with the photolysis of diazo compounds of type 36 (see Sect. 2.2), Wolff rearrangement (9%) and O/H insertion (6%) once again compete with thiophosphinic ester formation. Moreover, solvolysis of the P(S)/C(N2) bond 391 prevents a greater contribution of carbene products to the overall yield. 

Carbenes are commonly generated by irradiation or pyrolysis of an appropriate diazo-compound (2). Apart from differences readily traced to the change in temperature, the chemical properties of the carbenes formed from photolysis and from thermolysis are usually quite similar. These observations... 

Direct irradiation or thermolysis of a diazo-compound (2) is believed to generate the carbene initially in its singlet spin state. Triplet sensitization (5) is presumed to give the triplet carbene directly without first forming its singlet state via the triplet diazo-compound. In some cases, careful comparison of the results of direct irradiation experiments with those from triplet sensitization can provide useful information to identify the spin state initiating a reaction. 

Certain transition metal complexes catalyze the decomposition of diazo compounds. The metal-bonded carbene intermediates behave differently from the free species generated via photolysis or thermolysis of the corresponding carbene precursor. The first catalytic asymmetric cyclopropanation reaction was reported in 1966 when Nozaki et al.93 showed that the cyclopropane compound trans- 182 was obtained as the major product from the cyclopropanation of styrene with diazoacetate with an ee value of 6% (Scheme 5-56). This reaction was effected by a copper(II) complex 181 that bears a salicyladimine ligand. 

The photolysis or thermolysis of diazo compounds results in the formation of carbenes. These reactions were identified as early as 1901 by Hantzsch and Lehmann D and Staudinger and Kupfer who decomposed diazomethane photochemically and thermally, respectively. The subsequent work of Hine 3) and Doering ) started the era of carbene chemistry. Excellent reviews of the chemistry of carbenes are available 5-27),... 

Ando and co-workers have carried out photolysis and thermolysis on 2-alkylidene-l,3,4-thia-diazolines (34) synthesized from the thioketene (35) and diazo compounds (36). Irradiation of a benzene solution of (34) (R,R = —Me2C(CH2)2CMe2—) with a medium pressure mercury lamp produced (37) in a 51% yield, the bicyclo derivative (38) in a 15% yield, and a smaller amount of (35). In contrast, thermolysis of (34) at 130°C gave the thioketone (39) and the ethyne (40) in a quantitative yield. The episulfide (37) was isomerized quantitatively into the thiadiazoline (34) when treated with a trace of acid. A number of mechanisms were suggested for these transformations <90TL3571>. 

Catalyst-mediated decomposition of diazo compounds in the presence of C=S compounds has found application for the preparation of thiiranes in homogeneous systems (68,110,111). Recently, a convenient procedure for the preparation of geminal dichlorothiiranes from nonenolizable thioketones and chloroform under Makosza conditions was reported (112). Another approach to 2,2-dihalogenated thiiranes (e.g., 2,2-difluoro derivatives) involves the thermolysis of Seyferth reagents in the presence of thioketones (113,114a). Nucleophilic dimethoxycarbene was shown to add smoothly to adamantanethione to provide a unique approach to a thiiranone (5, 5 )-dimethylacetal (114b). 

Various ot,p y,5-unsaturated 1,3-dipoles are known to undergo 1,7-cyclization by a 871-electrocyclization process (329,330), and the corresponding diazo compounds behave similarly. 5-Diazopenta-l,3-diene derivatives such as 285 (Scheme 8.70), generated in situ by thermolysis of the corresponding tosylhydrazone sodium salts, cyclize to form 1,2-diazepines (286) (331). Sharp and co-workers studied the mechanism, scope, and limitations of this transformation. It was found that cis-substitution about the y,8-double bond prevents the 1,7-cyclization and directs the system toward 1,5-cyclization (332,333) (i.e., formation of a 3//-pyrazole), and that the ot,(3-double bond can be part of a phenyl ring (334). In special cases, the y,8-double bond can be incorporated as part of an aromatic [287 288 (335)] or 2- or 3-thienyl ring as well (336). 

The first carbene ever isolated was la, which was prepared using the most classical route to transient carbenes, namely, the decomposition of diazo compounds. The [bis(diisopropylamino)phosphino](trimethylsilyl)diazomethane precursor (la) was obtained by treatment of the lithium salt of trimethylsilyldiazomethane with 1 equiv of bis(diisopropylamino)chlorophosphine. Dinitrogen elimination occurs by photolysis (300 nm) or thermolysis (250 °C under vacuum) affording carbene la as a red oily material in 80% yield (Scheme 8.1). Carbene la is stable for weeks at room temperature and can even be purified by flash distillation under vacuum (10-2 Torr) at 75-80 °C. 

A potential problem in the use of diazo compounds as C atom precursors is the fact that intermediates in these reactions may act as C donors with the free atoms not involved. Indeed, the timing of the reactions in Eq. 6 is unknown and some of these intermediates may be bypassed in the thermolysis of 8. However, a comparison of the reactions of carbon from 8 with those of nucleogenic and arc generated carbon reveals quite similar products from many different substrates and provides circumstantial evidence for free C atoms in the decomposition of 8. 

This is a major route of decomposition of ethyl 2-furyldiazoacetate (%) (R = H, = C02Et) when heated in dichloromethane or methanol (74JOC2939). The same type of decomposition has been observed with other 2-furylcarbenes which were generated by decomposition of the sodium salts of tosylhydrazones at 3(X)°C (78JA7927). Thermolysis of the diazo compound 96 (R = R = H) in cyclooctane or styrene gave, besides the open-chain acetylene 97, products of intermolecular carbene insertion. This led the authors to favor the carbene mechanism of ring-opening (path A in Scheme 7). 

Monocyclic 1,3-oxazepines (325) with aryl substituents at the 2-, 4- and 7-positions can be prepared in moderate yield (20-40%) by the reaction of aliphatic diazo compounds with 1,3-oxazinium perchlorates (324) (74S187). Tetra- and penta-phenyl-l,3-oxazepines (328 R = H or Ph) have been obtained via the reaction of azide with pyrylium salts (326) (78H(l 1)331). This principle had earlier been applied to the preparation of 1,3-benzoxazepines (74CR(C)(278)1389> and more recently to 3,1-benzoxazepines (81JHC847). The preparation of 2-phenyl-1,3-oxazepine.(331) by the UV irradiation of (329) is mechanistically interesting in that it apparently involves an intermediate (330) of the same type as (327) (73TL1835), but the method has only been used in this one case. One of the few examples of a dihydro-1,3-oxazepine (333) has been prepared by the thermolysis of the aziridine (332) (68JOC4547). 

Certain transition metal complexes catalyze the decomposition of diazo compounds, where the metal-bound carbene intermediates behave differently from the free species generated by their photolysis or thermolysis. 

The reaction is assumed to involve initial formation of a carbene, by decomposition of the diazo compound with loss of nitrogen, followed by reaction of the electron-deficient carbene with the lone pair of electrons of the arsenic atom. Thermolysis of diazo compounds in copper-catalyzed reactions is known to provide singlet carbenes or carbenoid species (17). 

Diazomethane and its simple analogs undergo cycloaddition to unsaturated compounds both directly and after conversion to carbenes. The direct cycloadditions are 1,3-dipolar for the most part and provide access to pyrazolines and pyrazoles. Intramolecular cyclizations were recognized as early as 1965 95 The two main methods used in generation of diazo compounds for subsequent intramolecular cycloaddition include thermolysis of tosylhydrazone salts and thermolysis of iminoaziridines. Decomposition of nitros-amines has also been employed. 

The diazoacetonitrile-imine reaction may be considered complimentary to azide addition to cinnamonitriles because in the latter case only triazoline thermolysis products result.284 The reversed order of reactivity of the diazoacetonitrile to that of diazomethane implies an electrophilic attack on the imine and is explained in terms of a LUMOdi MC lonit[ile-HOMOin,int controlled interaction. Thus electron-rich enamines, which do not react with diazoalkanes, may be expected to react with electron-poor diazo compounds. 

The triazoline diazo compound equilibrium may be considered to play a role in the cis-trans isomerization332 and oxidation (Scheme 119)284 of certain triazolines. Triazole formation by elimination of amine214 or alcohol405 is also postulated to involve intermediate diazo compounds (Scheme 123). Unlike normal triazolines, the inability of 1-fluorotriazolines to undergo thermolysis or photolysis reactions to yield aziridines is ascribed to the fact that the triazoline always exists in equilibrium with the diazo compound (Scheme 98).356 Spontaneous isomerizations of triazolines not... 

Enamine formation occurs by the thermolysis of diazo compounds (Scheme 150)67 109,278 284 288,304 332 453 454 via a carbene-like intermediate.284 332 When R1 = Ph, it enters into competition with hydrogen migration,284,332 and the electrophilic character of the carbene enhances the migration of the dimethylaminophenyl more than the phenyl.332 When triazoline synthesis is carried out at temperatures higher than that at which thermolysis of diazo compounds occurs, enamines are obtained exclusively, as in the addition of phenyl azide to cinnamic nitriles and ketones, with phenyl migration dominating in the nitrile.284 Enamine is also formed quantitatively in the reaction of ethyl diazoacetate with benzylideneaniline at 110°C.455... 

Triazoline thermolysis leads to aziridines, diazo compounds, imines, or enamines a diazonium betaine is postulated as the intermediate that can undergo stabilization by different pathways,16,30,806,112,465 as depicted in Scheme 161. Imine and enamine formation may occur directly from the diazonium betaine806,112,226 237 247 or via the diazo compound.32 Acceleration of the rate of thermolysis of 4,5-dialkyl-substituted triazolines in polar solvents is commensurate with the betaine intermediate,100,112,457,466 and attempts to prove a 1,3-zwitterionic intermediate have failed 467-469... 

Azide addition to open-chain vinyl ethers results in different thermolysis products, depending on the azide and the enol ether employed. In Scheme 180, when R = benzoyl or ethoxycarbonyl, R2 = OR1 and R3 = H, imino ethers are obtained by alkoxyl migration along with minor amounts of azir-idine.269 525 However, when R = Ph and the carbons are fully substituted, the imine (108) is obtained apparently from the reversibility of the imine-diazo compound addition (Section IV,B,2) (Scheme 181).270... 

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