Diazoalkanes carbene formation

The most common byproducts encountered in cyclopropanations with diazoalkanes as carbene precursors are azines and carbene dimers , i.e. symmetric olefins resulting from the reaction of the intermediate carbene complex with the diazoalkane. The formation of these byproducts can be supressed by keeping the concentration of diazoalkane in the reaction mixture as low as possible. For this purpose, the automated, slow addition of the diazoalkane to a mixture of catalyst and substrate (e.g. by means of a pump or a syringe motor) has proven to be a very valuable technique. 

The complications that occasionally arise in the use of diazoalkanes reflect the possible further reactions of carbene ligands, which will be dealt with subsequently, e.g. insertion into adjacent M-H or M-halide bonds and the formation of bimetallic complexes supported by bridging carbene ligands. In some cases, transition metals may catalyse reactions of diazoalkanes, leading to products which are suggestive of the reactions of free carbenes, i.e. dimerization, addition to alkenes (cyclo-propanation) and insertion into C-H bonds (Figure 5.9). In such cases, however, the actual mechanism does not involve free carbenes but rather transient diazoalkane/carbene complexes. This is supported by the obser-... 

Ketone 4-toluenesulfonylhydrazone salts can be used for carbene formation. The mild thermolysis and the photolysis of these salts leading to diazoalkanes are known as the Bamford-Stevens reaction. If run under more energetic conditions, the metastable diazoalkanes form carbenes and their subsequent products (e.g., alkenes), or, in the presence of mild acids, products of carbocations (see Subsect. 2.5.2). 

Interestingly, Dixneuf has shown recently that vinyl metal carbenoid intermediate 176 generated with an electrophilic ruthenium catalyst [RuCl(cod)Cp ] (Cp = CsMes) could be trapped by a diazoalkane carbene to yield acetoxy dienes 186 through carbene dimerization, in good yields (Scheme 77) [162], No dimerization product and no cyclopropane formation could be noticed even when the reaction was run in the beneficial presence of 5 equiv. of styrene. 

The stereochemistry of the ring product (17) was rationalized in terms of the attraction and repulsion between the involved substituents98. The accompanying olefins may be formed via carbene intermediates (arising from a-elimination of S02 from sulfene), and the intermediacy of thiadiazoline dioxide (from sulfene and diazoalkane) explains the formation of the ketazine side-products. Thiadiazoline, on its part, may be formed directly by the cyclization of zwitterion 101. 

Catalytic cyclopropanation of alkenes has been reported by the use of diazoalkanes and electron-rich olefins in the presence of catalytic amounts of pentacarbonyl(rj2-ris-cyclooctene)chromium [23a,b] (Scheme 6) and by treatment of conjugated ene-yne ketone derivatives with different alkyl- and donor-substituted alkenes in the presence of a catalytic amount of pentacarbon-ylchromium tetrahydrofuran complex [23c]. These [2S+1C] cycloaddition reactions catalysed by a Cr(0) complex proceed at room temperature and involve the formation of a non-heteroatom-stabilised carbene complex as intermediate. 

Carbenes from Sulfonylhydrazones. The second method listed in Scheme 10.8, thermal or photochemical decomposition of salts of arenesulfonylhy-drazones, is actually a variation of the diazoalkane method, since diazo compounds are intermediates. The conditions of the decomposition are usually such that the diazo compound reacts immediately on formation.147 The nature of the solvent plays an important role in the outcome of sulfonylhydrazone decompositions. In protic solvents, the diazoalkane can be diverted to a carbocation by protonation.148 Aprotic solvents favor decomposition via the carbene pathway. 

A Mechanism for Alkylidene Formation. There is no unambiguous example of free-carbene capture by a metal substrate, and the mild reaction conditions used in the generation of these carbene complexes from diazoalkanes suggests that such a mechanism is highly unlikely here. Transition metal diazoalkane complexes, then, are almost certainly implicated as intermediates in these reactions. 

For the formation of stilbenes from aryldiazomethanes, Rh2(OAc)4 was shown to be superior to other catalysts such as CufClO or CuBr2 357), LiBr363 or Ce(NH4)2(N03)6 364) in terms of efficiency, Z-selectivity and compatibility with substituents on the aromatic ring of the diazoalkane 358 . Even higher Z-selectivity was provided by the bulky catalyst iodorhodium(III) mew-tetraphenylporphyrin, but reduced yields had to be acknowledged358 . Contrary to copper catalysts, RhjfOAc failed to induce the formation of carbene dimers from secondary aryldiazoalkanes azines were produced instead 358). 

The EfZ ratio of stilbenes obtained in the Rh2(OAc)4-catalyzed reaction was independent of catalyst concentration in the range given in Table 22 357). This fact differs from the copper-catalyzed decomposition of ethyl diazoacetate, where the ratio diethyl fumarate diethyl maleate was found to depend on the concentration of the catalyst, requiring two competing mechanistic pathways to be taken into account 365), The preference for the Z-stilbene upon C ClO -or rhodium-catalyzed decomposition of aryldiazomethanes may be explained by the mechanism given in Scheme 39. Nucleophilic attack of the diazoalkane at the presumed metal carbene leads to two epimeric diazonium intermediates 385, the sterically less encumbered of which yields the Z-stilbene after C/C rotation 357,358). Thus, steric effects, favoring 385a over 385 b, ultimately cause the preferred formation of the thermodynamically less stable cis-stilbene. 

Some examples of carbene dimer formation resulting from diazoalkane decomposition on transition-metal surfaces have been reported. Diazomethane is decomposed to give ethylene and N2 upon passage over a C0O/M0O3 catalyst as well as on Ni, Pd, Fe, Co, Ru and Cu surfaces 367). Similarly, 2-diazopropane is readily decomposed on Raney nickel 368). At room temperature, propene and N2 were the only detectable products, but above 50 °C, the carbene dimer 2,3-dimethyl-2-butene started to appear which reached its maximum yield at 100 °C, where approximately 40 % of the carbene fragments dimerized. It is assumed 367,368), that surface carbenes are formed as intermediates from both diazomethane and 2-diazopropane which either dimerize or desorb by migration of a P-hydrogren, if available (Scheme 40). 

The q1-coordinated carbene complexes 421 (R = Ph)411 and 422412) are rather stable thermally. As metal-free product of thermal decomposition [421 (R = Ph) 110 °C, 422 PPh3, 105 °C], one finds the formal carbene dimer, tetraphenylethylene, in both cases. Carbene transfer from 422 onto 1,1-diphenylethylene does not occur, however. Among all isolated carbene complexes, 422 may be considered the only connecting link between stoichiometric diazoalkane reactions and catalytic decomposition [except for the somewhat different results with rhodium(III) porphyrins, see above] 422 is obtained from diazodiphenylmethane and [Rh(CO)2Cl]2, which is also known to be an efficient catalyst for cyclopropanation and S-ylide formation with diazoesters 66). 

By analogy with cyclopropane formation from carbenes and C=C bonds, azo compounds might be expected to give diaziridines in their reaction with carbenes. Although acyclic ADC compounds react readily with diazoalkanes... 

Most significant is the formation of 92 in all thermolysis reactions of 91. This result is consistent with the sequence 91 -> diazoalkane of type 94 — carbene 52 - bridgehead olefin 53 - carbene 54 — H shift to afford 92. Formation of olefin 93 is best interpreted by H shift from the methyl group of carbene 52 (X=/-Bu, Y=Me) to the carbonic carbon, whereas 95 is formed by insertion of the carbenic center of 52 (X=Y=r-Bu) into the C-H bond of the r-Bu group. 

By analogy with the intramolecular insertion of phenylthiocarbenes, the reaction of (oo-oxido)diazoalkanes 93 resulted in the formation of cycloalkenes 94.38 However, the reaction was proven to proceed not via a carbene route b but a nitrene route a as shown in Scheme 26. The nitrene route is supported by the formation of heterocyclic products 98 and 99.39 This insertion reaction was used in the cydization step to the cyclopentene ring formation of isocarbacycline 97.40... 

The transition metal-catalyzed cyclopropanation of alkenes is one of the most efficient methods for the preparation of cyclopropanes. In 1959 Dull and Abend reported [617] their finding that treatment of ketene diethylacetal with diazomethane in the presence of catalytic amounts of copper(I) bromide leads to the formation of cyclopropanone diethylacetal. The same year Wittig described the cyclopropanation of cyclohexene with diazomethane and zinc(II) iodide [494]. Since then many variations and improvements of this reaction have been reported. Today a large number of transition metal complexes are known which react with diazoalkanes or other carbene precursors to yield intermediates capable of cyclopropanating olefins (Figure 3.32). However, from the commonly used catalysts of this type (rhodium(II) or palladium(II) carboxylates, copper salts) no carbene complexes have yet been identified spectroscopically. 

Most electrophilic carbene complexes with hydrogen at Cjj will undergo fast 1,2-proton migration with subsequent elimination of the metal and formation of an alkene. For this reason, transition metal-catalyzed cyclopropanations with non-acceptor-substituted diazoalkanes have mainly been limited to the use of diazomethane, aryl-, and diaryldiazomethanes (Tables 3.4 and 3.5). 

The normal byproducts formed during the transition metal-catalyzed decomposition of diazoalkanes are carbene dimers and azines [496,1023,1329], These products result from the reaction of carbene complexes with the carbene precursor. Their formation can be suppressed by slow addition (e.g. with a syringe motor) of a dilute solution of the diazo compound to the mixture of substrate and catalyst. Carbene dimerization can, however, also be a synthetically useful process. If, e.g., diazoacetone is treated with 0.1% RuClCpIPPhjij at 65 °C in toluene, cw-3-hexene-2,5-dione is obtained in 81% yield with high stereoselectivity [1038]. 

Reaction of diazo compounds with a variety of transition metal compounds leads to evolution of nitrogen and formation of products of the same general type as those formed by thermal and photochemical decomposition of diazoalkanes. These transition metal-catalyzed reactions in general appear to involve carbenoid intermediates in which the carbene becomes bound to the metal.83 The metals which have been used most frequently in synthesis are copper and rhodium. 

The formation of cyclopropane derivatives by photolysis of diazoalkanes in the presence of alkenes is believed to occur by photolytic decomposition of the diazoalkane to yield the carbene, followed by addition of this carbene to the alkene. Cycloaddition of this type has been reported in furan, dihydrofuran, and thiophene.198 Thus, photolysis of ethyl diazoacetate in thiophene yields the bicyclic sulfur heterocycle (215). Alternatively, photolysis of 3-diazo-l-methyl-oxindole (216) in cyclohexene leads to the formation of two isomers which are thought to have the spirocyclopropyl structure (217) photolysis in ethanol yields 3-ethoxy-1-methyloxindole.194... 

Diazocarbonyl compounds, especially diazo ketones and diazo esters [19], are the most suitable substrates for metal carbene transformations catalyzed by Cu or Rh compounds. Diazoalkanes are less useful owing to more pronounced carbene dimer formation that competes with, for example, cyclopropanation [7]. This competing reaction occurs by electrophilic addition of the metal-stabilized carbocation to the diazo compound followed by dinitrogen loss and formation of the alkene product that occurs with regeneration of the catalytically active metal complex (Eq. 5.5) [201. 

The thermal decomposition of diazoalkanes is also a reaction in which the involvement of carbenes is often assumed. In both photolytic and thermal decompositions in aprotic solvents, insertion products are accompanied by dimeric azines and olefins (equation 4). Their formation... 

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