Diazo dimerization

The range of diazo compounds that can be used in this catalytic cycle is limited. Diazomethane is not compatible with the system as diazo dimerization occurs instead of ylide formation [16,17]. Diazoacetates cannot be used as the corresponding sulfur ylides are too stable and are known not to react with simple aldehydes [ 18,19,20,21 ]. As it was known that sulfur ylides stabilized by amides are sufficiently reactive to add to aldehydes [18,22,23,24,25], diazo acetamides... 

Breakdown of the sulphamido group does not occur in alkaline solutions, but strong adds can degrade it (Fig. 4.36). Sulphonamides are generally photosensitive because of the reactivity of the primary amine at position 4. This group is oxidised under the catalytic action of light to produce diazo dimers. 

However, the diazo dimer is still susceptible to further oxidation. This leads to the oxidation of the benzene ting (Fig. 4.37). Protecting the sulphonamide solution from... 

A solution of ethyl diazo(2,4,6-trimethyl-4//-pyran-4-yl)acetate (0.47 g, 2.0 mmol) in benzene (50 mL) was stirred with // -allylpalladium chloride dimer (15 mg) for 2h at rt, and then the solvent was evaporated. The residue was chromatographed (80-g basic alumina, EtOAc/hexane 1 2) yield 0.40 g (97 %) yellow oil. 

This reaction can also be used for the synthesis of substituted 1-benzoxepins with one modification instead of the 4/T-benzopyran the 2/7-isomer must be used. 2-[Diazo(phosphoryl)meth-yl]-2//-benzopyrans decompose in the presence of ))3-allylpalladium chloride dimer with elimination of nitrogen to give 1-benzoxepins 2.192 In some cases, the reaction takes a different course and gives 2-methylene-2//-benzopyrans 3.192 In this respect, the bicyclic system behaves differently to the monocyclic diazo(pyranyl)methane. The 2-isomers of the latter structure could not be isolated and gave l//-l,2-diazepines.190 The 4//-benzopyrans do not form benzoxepins but undergo an intramolecular [2+1] cycloaddition to 3,4-dihydro-2,3,4-metheno-2//-ben-... 

Dibenzo[/>,rf]thiopyrylium tetrafluoroborate (1) reacts with ethyl lithiodiazoacetate at — 120 C to form the diazo compound 2 which, with dimeric ( 3-allyl)chloropalIadium at 20 C, gives ethyl dibenzo[ ,d]thiepin-6-carboxylate (3), via a carbene intermediate.5 Compound 3 is quite stable the ethoxycarbonyl group can be hydrolyzed by alkali and decarboxylated to give the corresponding parent compound 4 in good yield. 

The synthesis of thiepins 14 was unsuccessful in the case of R1 = i-Pr,79 but if the substituents in the ortho positions to sulfur arc /erf-butyl, then thiepin 14 (R1 = t-Bu R2 = Me) can be isolated in 99% yield.80 Rearrangement of diazo compound 13 (R1 = t-Bu R2 = H), which does not contain the methyl group in position 4, catalyzed by dimeric ( y3-allyl)chloropalladium gives, however, the corresponding e.w-methylene compound. The thiepin 14 (R1 = t-Bu, R2 = H) can be obtained in low yield (13 %) by treatment of the diazo compound with anhydrous hydrogen chloride in diethyl ether at — 20 C.13 In contrast, the ethyl thiepin-3,5-or -4,5-dicarboxylates can be prepared by the palladium catalysis method in satisfying yields.81... 

Dimeric heterocyclic compounds 206 (R, R = Ph, Ph Ph, MeO MeO MeO) were prepared by treatment of diazo-4//-thiopyrans 203a, 203b, and 203e with 2,4,6-triphenylthiopyrylium salt 48e in an Et3N-CHCl3 solution at 20°C. A mechanism is discussed in detail (85T811). 

Quinone diazides can also be obtained by the diazo group transfer reaction of 4-tosyl azide. For example, 9-diazo-10-anthrone (2.55) is formed from anthrone (2.54) if the reaction is carried out in an ethanol-piperidine mixture. On the other hand, if ethanol is replaced by pyridine, dimerization with loss of molecular nitrogen takes place and the azine 2.56 is isolated (Scheme 2-32 Regitz, 1964 Cauquis et al., 1965). In the preceding discussion tosyl azide was shown to be an electrophilic reagent. It therefore seems likely that it is not the anthrone 2.54 but its conjugate base which reacts with tosyl azide. 

Zollinger (1971) calculated the actual rate constant referring to the monomeric diazo component from the (overall) measured rates and the dimerization equilibrium constant. The ratio of rates of the first to the second azo coupling reaction of the biphenyl-4,4 -bis-diazonium ion with the trianion of 2-naphthol-3,6-disulfonic acid at 15 °C, k /k2 9 is 80. 

The readily accessible dibenzothiapyrylium salt (62)m reacts with ethyl lithio diazoacetate 47) in a 1 1 mixture of ether and tetrahydrofuran at —120 °C to form the diazo compound (65). Treatment of 65 with 5 mol-% of it-allylpalladium chloride dimer in a 1 2 mixture of chloroform and carbon tetrachloride at 0 °C and... 

Herrmann has reported the reaction of the mercury diazo compound Hg(CN2C02Et)2 with Mn(CO)sBr to afford the biscarbyne-bridged dimer 90 (128). The intermediacy of a terminal mononuclear carbyne complex 89 is strongly implicated here ... 

The common by-products obtained in the transition-metal catalyzed reactions are the formal carbene dimers, diethyl maleate and diethyl fumarate. In accordance with the assumption that they owe their formation to the competition of olefin and excess diazo ester for an intermediate metal carbene, they can be widely suppressed by keeping the actual concentration of diazo compound as low as possible. Usually, one attempts to verify this condition by slow addition of the diazo compound to an excess (usually five- to tenfold) of olefin. This means that the addition rate will be crucial for the yields of cyclopropanes and carbene dimers. For example, Rh6(CO)16-catalyzed cyclopropanation of -butyl vinyl ether with ethyl diazoacetate proceeds in 69% yield when EDA is added during 30 minutes, but it increases to 87 % for a 6 h period. For styrene, the same differences were observed 65). 

Rhodium(II) acetate was found to be much more superior to copper catalysts in catalyzing reactions between thiophenes and diazoesters or diazoketones 246 K The outcome of the reaction depends on the particular diazo compound 246> With /-butyl diazoacetate, high-yield cydopropanation takes place, yielding 6-eco-substituted thiabicyclohexene 262. Dimethyl or diethyl diazomalonate, upon Rh2(OAc)4-catalysis at room temperature, furnish stable thiophenium bis(alkoxycarbonyl)methanides 263, but exclusively the corresponding carbene dimer upon heating. In contrast, only 2-thienylmalonate (36 %) and carbene dimer were obtained upon heating the reactants for 8 days in the presence of Cul P(OEt)3. The Rh(II)-promoted ylide formation... 

Occurence of olefins which are, formally speaking carbene dimers, as well as of similar products (R2C=N—N=CR2, R2CH—CHR2) represents an usually unwanted side-reaction which the chemist endeavors to suppress as far as possible. Nevertheless, conditions for high-yield synthesis of carbene dimers from several diazo compounds have been reported in the past13,141. Some novel examples, published since the last review14) was written, are listed in Table 22. 

Table 22. Carbene dimers by catalytic decomposition of diazo compounds... 

Ifcobs is directly proportional to pyridine concentration. Therefore a plot of kobs vs. [pyridine] is linear, with a slope (k ) equal to the second order rate constant for ylide formation, and an intercept (k0) equal to the sum of all processes that destroy the carbene in the absence of pyridine (e.g.) intramolecular reactions, carbene dimerization, reactions with solvent, and, in the case of diazirine or diazo carbene precursors, azine formation. 

An important competing process with significant practical consequences is the catalytic dimerization of diazoacetate to form maleate and fumarate esters. Most catalysts suffer from this side reaction, leading to the use of the alkene as solvent in order to accelerate the productive pathway and the slow addition of diazo compound in order to minimize dimerization. Since this problem is generally shared across most catalyst architectures, it will be mentioned in discussions of individual asymmetric catalyst systems only in those instances where these precautions prove to be unnecessary. 

The aggregation and tautomeric equilibria of Cl Acid Red 138 (3.10) have been examined recently. In spite of the length of the dodecyl substituent in the diazo component only monomers and dimers were present [16], presumably because the H acid residue contributes two sulpho groups to solubilise the molecule. Both monomer and dimer species were predominantly in the hydrazone form, as expected, and hydrophobic interaction between the terminal dodecyl chains played an important part in formation of the dimer. 

Diazo components may also be of some significance in defining absorption frequencies. An amine with a considerably enlarged conjugated system, made, for instance, by dimerization, can contribute to a considerable bathochromic shift. Examples include the following ... 

The catalytic activity of rhodium diacetate compounds in the decomposition of diazo compounds was discovered by Teyssie in 1973 [12] for a reaction of ethyl diazoacetate with water, alcohols, and weak acids to give the carbene inserted alcohol, ether, or ester product. This was soon followed by cyclopropanation. Rhodium(II) acetates form stable dimeric complexes containing four bridging carboxylates and a rhodium-rhodium bond (Figure 17.8). 

Flash photolysis of 5-diazo-lO, ll-dihydro-dibenzo[a, d]cycloheptene (75) — which can be regarded as a bridged diphenyl-carbene — at room temperature in hquid paraffin first produced the spectrum of the triplet carbene 16, which then disappeared to give the electronic spectrum of the radical 17. The latter finally gave the dimer 5,5 -bi (10, ll-dihydrodibenzo[a, djcycloheptenyl) 18 2). 

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]. 

The reaction of (trialkylsilyl)vinylketenes with nucleophilic carbenoid reagents, such as sulfur ylides and diazo compounds, has been used for synthesis of substituted cyclopentenones by stereoselective 4 + 1-annulation (Scheme 12). The strategy relies on the remarkable ability of silyl substituents to stabilize ketenes and suppress their tendency to undergo dimerization and 2 - - 2-cycloaddition. 

In search of a convenient procedure for preparing diazo substrates for the cycloaddition to Cgg, Wudl introduced the base-induced decomposition of tosyl-hydrazones [116]. This procedure allows the in situ generation of the diazo compoimd without the requirement of its purification prior to addition to Cgg. Since they are rapidly trapped by the fullerene, even unstable diazo compounds can be successfully used in the 1,3-dipolar cycloaddition. In a one-pot reaction the tosyUiydrazone is converted into its anion with bases such as sodium methoxide or butylHfhium, which after decomposition readily adds to Cgg (at about 70 °C). This method was first proven to be successful with substrate 142. Some more reactions that indicate the versatility of this procedure are shown in Table 4.4. Reaction of 142 with CgQ under the previously described conditions and subsequent deprotection of the tert-butyl ester leads to [6,6]-phenyl-C5j-butyric acid (PCBA) that can easily be functionalized by esterification or amide-formation [116]. PCBA was used to obtain the already described binaphthyl-dimer (obtained from 149 by twofold addition) in a DCC-coupling reaction [122]. 

Thermolysis of 2-diazo-l,3-dithiane, prepared in situ from the reaction of 2-lithio-2-trimethylsilyl-l,3-dithiane and tosyl azide, occurs already below 0°C. The resulting carbene dimerizes efficiently even in the presence of alkenes and alkynes to give bis(l,3-dithianylidene) in 78% yield (Scheme 41) <1997T9269>. 

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