Acceptor-substituted diazomethanes

The most frequently used ylides for carbene-complex generation are acceptor-substituted diazomethanes. As already mentioned in Section 3.1.3.1, non-acceptor-substituted diazoalkanes are strong C-nucleophiles, easy to convert into carbene complexes with a broad variety of transition metal complexes. Acceptor-substituted diazomethanes are, however, less nucleophilic (and more stable) than non-acceptor-substituted diazoalkanes, and require catalysts of higher electrophilicity to be efficiently decomposed. Not surprisingly, the very stable bis-acceptor-substituted diazomethanes can be converted into carbene complexes only with strongly electrophilic catalysts. This order of reactivity towards electrophilic transition metal complexes correlates with the reactivity of diazoalkanes towards other electrophiles, such as Brpnsted acids or acyl halides. 

The great popularity of diazocompounds as carbene complex precursors is mainly because of the ease of their preparation and handling. In addition to this, catalytic diazodecompositions often proceed very cleanly and in high yields. Acceptor-substituted diazomethanes can be prepared in several different ways (Figure 4.2). 

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

When 2-alkyl-3-keto esters or 2-aryl-3-keto esters are treated with sulfonyl azides under basic conditions, nucleophilic deacylation occurs to yield 2-alkyl/aryl-2-diazo esters [960-963]. Nucleophilic deacylation can also be used to convert acceptor-substituted diazoketones into the corresponding acceptor-substituted diazomethanes [964,965]. In all these deacylation reactions it is the most electrophilic carbonyl group which is attacked by the nucleophile and cleaved off. 

Fig. 4.2. Synthetic routes to acceptor-substituted diazomethanes. Z, Z electron-...

Acceptor-substituted diazomethanes can be explosive, and low-molecular-weight diazo compounds, in particular, should be handled with care. Ethyl diazoacetate has a half-life of 109h at 100°C in inert solvents [984, p 425], but traces of acid or catalytically active salts can dramatically accelerate the thermal decomposition. Monoacyldiazomethanes are thermally less stable than diazoacetates [985], whereas bis-acceptor-substituted diazomethanes generally have high thermal and chemical stability. 

Table 4.1. Transition metal complexes suitable for the conversion of acceptor-substituted diazomethanes into carbene complexes.

Different catalysts suitable for the conversion of acceptor-substituted diazomethanes into carbene complexes are listed in Table 4.1. Of these, the very efficient rhodium(II) and copper(I) complexes are by far the most commonly used catalysts. For a comparative study of several different catalysts, see [986]. 

Ylides other than acceptor-substituted diazomethanes have only occasionally been used as carbene-complex precursors. lodonium ylides (PhI=CZ Z ) [1017,1050-1056], sulfonium ylides [673], sulfoxonium ylides [1057] and thiophenium ylides [1058,1059] react with electrophilic transition metal complexes to yield intermediates capable of undergoing C-H or N-H insertions and olefin cyclopropanations. 

The conversion of acceptor-substituted diazomethanes into carbene complexes often does not proceed smoothly in the presence of sulfides. This might be because of poisoning of the catalyst by the sulfide [975]. Higher yields of sulfonium ylides can, however, be obtained by HBF4-mediated reaction of acceptor-substituted diazomethanes with sulfides [1011,1328,1330,1331]. 

When planning reactions of thiocarbonyl compounds with electrophilic carbene complexes it should be taken into aceount that thiocarbonyl compounds can undergo uncatalyzed 1,3-dipolar cycloaddition with acceptor-substituted diazomethanes to yield 1,3,4-thiadiazoles. These can either be stable or eliminate nitrogen to yield thiiranes or other products similar to those resulting from thiocarbonyl ylides [1338]. 

Fig. 4.20. Complexes for asymmetric cyclopropanation with acceptor-substituted diazomethanes. 1 [1372], 2 [1373], 3 [1033], Rh2(55-MEPY>4, Rh2(55-MPPIM)4 [1001,1074], For related rhodium-based catalysts, see, e.g., [997,1000,1002].

Numerous carbene complexes have since been prepared by this method [1,52,60,499-503], even utilizing highly reactive diazoalkanes such as diazomethane [504], Because of their high nucleophilicity and reactivity, non-acceptor-substituted diazoalkanes can displace even strongly bound ligands, such as phosphines. Examples of such reactions are shown in Figure 3.20. 

Transition metal complexes which react with diazoalkanes to yield carbene complexes can be catalysts for diazodecomposition (see Section 4.1). In addition to the requirements mentioned above (free coordination site, electrophi-licity), transition metal complexes can catalyze the decomposition of diazoalkanes if the corresponding carbene complexes are capable of transferring the carbene fragment to a substrate with simultaneous regeneration of the original complex. Metal carbonyls of chromium, iron, cobalt, nickel, molybdenum, and tungsten all catalyze the decomposition of diazomethane [493]. Other related catalysts are (CO)5W=C(OMe)Ph [509], [Cp(CO)2Fe(THF)][BF4] [510,511], and (CO)5Cr(COD) [52,512]. These compounds are sufficiently electrophilic to catalyze the decomposition of weakly nucleophilic, acceptor-substituted diazoalkanes. 

The transition metal-catalyzed reaction of diazoalkanes with acceptor-substituted alkenes is far more intricate than reaction with simple alkenes. With acceptor-substituted alkenes the diazoalkane can undergo (transition metal-catalyzed) 1,3-dipolar cycloaddition to the olefin [651-654]. The resulting 3//-pyrazolines can either be stable or can isomerize to l//-pyrazolines. 3//-Pyrazolines can also eliminate nitrogen and collapse to cyclopropanes, even at low temperatures. Despite these potential side-reactions, several examples of catalyzed cyclopropanations of acceptor-substituted alkenes with diazoalkanes have been reported [648,655]. Substituted 2-cyclohexenones or cinnamates [642,656] have been cyclopropanated in excellent yields by treatment with diazomethane/palladium(II) acetate. Maleates, fumarates, or acrylates [642,657], on the other hand, cannot, however, be cyclopropanated under these conditions. 

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). 

Diazomethane is an electron-rich 1,3-dipole, and it therefore engages in Sustmann type I 1,3-dipolar cycloadditions. In other words, diazomethane reacts with acceptor-substituted alkenes or alkynes (e. g., acrylic acid esters and their derivatives) much faster than with ethene or acetylene (Figure 15.36). Diazomethane often reacts with unsymmetrical electron-deficient... 

According to Scheme 1 methyl 2-siloxycyclopropanecarboxylates should also be available from donor-acceptor-substituted olefins like 100, which are easily synthesized by silylation of the corresponding 1,3-dicarbonyl compounds. Cyclopropanation of 100 with methyl diazoacetate or diazomethane could be realized in the presence of Cu(II)-catalysts, but due to the relatively low reactivity of the olefins a large excess of diazoalkanes had to be employed. This makes the isolation of 101 troublesome and therefore direct hydrolysis with acid to give 1,4-dicarbonyl compounds 102 is advantageous (Eq. 32) 66). 

Primary cycloaddition products are the 3H-pyrazoles 22, which tautomerize to the IH-pyrazoles 23. With unsymmetrical alkynes, the regiochemistry of diazoalkane cycloaddition is ambivalent and dependent on sterical and electronic effects [324]. Mono-acceptor-substituted alkynes react regioselectively for instance, propargylaldehyde and diazomethane lead to the pyrazole-5-aldehyde (25), which equilibrates with its annular 3-tautomer 24 ... 

This fragmentation of the heparin heteropolysaccharide chain proved to be a jS-elimination reaction in which diazomethane acts as the proton acceptor. It is interesting that aryldiazoalkanes (for example, phenyl or substituted-phenyl diazomethanes) cannot be used for a similar j8-eliminative degradation of quaternary ammonium salts of sulfated heteropolysaccharides. 

Because of enormous richness of possible combinations of individual components it is very difficult to make in these cases some generalizations and every reaction has to be analyzed individually. From a number of examples where such an analysis was performed [44,45], it is possible to mention the model case of the addition of substituted ethenes to diazomethane. As can be seen from the scheme, in the case of alkenes substituted by acceptor substituents the reaction is governed by the interactions HOMO ipoi - LUMOdipoiaroffh whereas in the case of donor substitution the interactions - LUMO pQi dominate. The result of... 

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