Stability of diazo compounds

One of the major drawbacks of the diazoacetyl group was its instability at low pH and its reactivity in the dark towards protein functional groups (see Section 4.7.2). The 2-diazo-3,3,3-trifluoropropionyl and p-toluenesul-fonyldiazoacetyl groups are considerably improved in these respects and are stable in 1 M hydrochloric acid. 

Like aryl azides, diazo compounds are susceptible to reduction by thiols and a study of the diazotrifluoropropionyl group has been made by Taka-gaki et al. (1980) who showed that the corresponding hydrazone is formed (Fig. 3.6). For example, one reagent 20 pM) was converted to the extent of 24% in 3 h at room temperature by 30 mM cysteine, at pH 8.0. 

While azides were far more susceptible to reduction by dithiols, the rates of reduction of a diazotrifluoropropionyl derivative by dithiothreitol, (3-mercaptoethanol, cysteine, and reduced glutathione did not differ widely. Thioglycolic acid was however a poor reductant and it was suggested that it should be used to replace (3-mercaptoethanol or DTT when diazo reagents are used. The reduction may be monitored by TLC or by a 500-fold increase in the absorbance at 260 nm. 

The stability of a prospective diazo reagent in the dark should further be ensured by a careful consideration of its structural features. A problem that was encountered with A6-diazomalonoyl cAMP was the Dimroth rearrangement (Fig. 3.7). 

A more subtle question concerns the two rotational isomers of diazo compounds with a-keto groups (Fig. 3.8). 

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Excess diazomethane has been used to convert phenols to methyl ethers in the presence or absence of acids . Employment of transition metal derivatives, typically Rh2(OAc)4 and recently CHsReOs , allows one to react functionalized diazo compounds in an intramolecular or intermolecular 0-aUtylation (equation 13). The stability of diazo compounds derived from active methylene compounds toward OH insertion was compared... 

Diazo compounds constitute the most common class of carbene precursors. The stability of diazo compounds is very much influenced by the substituents present. Simple diazoalkanes such as diazomethane tend to be rather unstable and because... 

TGA and DTA curves of BTf and ITf are shown in Fig. 2. The degradation temperature Td of BP was the highest of the diazo compounds studied as shown in Table 1. In the case of common diazonium cation, Td of BP is higher than that of BTf The thermal stability of diazo compounds depended on the counter anion. Td of IP was higher than that of ITf, which is in the same correlation to BP and BTf Td of the diazo compounds was lower than that of the iodonium salts with the same counter anion. 

Nevertheless, a more traditional approach to the stabilization of carbenes and the investigation of their spectral properties deals with the direct generation of carbenes in low-temperature matrices, e.g. by the photolysis of diazo-compounds or ketenes. The method allows stabilization of carbenes in their ground electronic state, prevents intramolecular isomerization and also facilitates direct spectroscopic monitoring of their chemical transformations in low-temperature matrices. 

Carbenes from Diazo Compounds. Decomposition of diazo compounds to form carbenes is a quite general reaction that is applicable to diazomethane and other diazoalkanes, diazoalkenes, and diazo compounds with aryl and acyl substituents. The main restrictions on this method are the limitations on synthesis and limited stability of the diazo compounds. The smaller diazoalkanes are toxic and potentially explosive, and they are usually prepared immediately before use. The most general synthetic routes involve base-catalyzed decomposition of V-nitroso derivatives of amides, ureas, or sulfonamides, as illustrated by several reactions used for the preparation of diazomethane. 

Interaction of an electrophilic carbene or carbenoid with R—S—R compounds often results in the formation of sulfonium ylides. If the carbene substituents are suited to effectively stabilize a negative charge, these ylides are likely to be isolable otherwiese, their intermediary occurence may become evident from products of further transformation. Ando 152 b) has given an informative review on sulfonium ylide chemistry, including their formation by photochemical or copper-catalyzed decomposition of diazocarbonyl compounds. More recent examples, including the generation and reactions of ylides obtained by metal-catalyzed decomposition of diazo compounds in the presence of thiophenes (Sect. 4.2), allyl sulfides and allyl dithioketals (Sect. 2.3.4) have already been presented. 

Homolytic cleavage of diazo compounds such as AIBN is also driven by the stability of a neutral molecule, this time molecular nitrogen, and two alkyl radicals are produced. 

Two general methods are available for tbe assembly of tbe sterically stabilized species 16-24, both starting from metallic derivatives of diazo compounds (147) (16). Tbe latter have two nucleopbilic centers and can, in principle, react with electrophiles at C giving the functionalized diazo compounds (148), or at N, which... 

Diazomethylene)phosphoranes 33 (Scheme 8.10), which represent another type of diazocumulenes (12) are easily obtained by the oxidative ylidation of the corresponding phosphanyl(trimethylsilyl)diazomethane with CCI4. The increased stability of these compounds as compared with diazocumulenes (R2C=C=N2) is probably due to the ylidic character of the P=C bond. These diazo compounds exhibit the expected dipolar reactivity toward electron-deficient alkenes, alkynes, phosphaalkenes, and heterocumulenes (12). Thus, 33 reacts with TCNE to form A -pyrazoline 35 (60). Furthermore, 33 could be converted into the phosphonio-borate-substituted diazo compound 34, which underwent subsequent cycloaddition with electron-deficient alkenes (e.g., 34 36) (61). 

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

A select number of transition metal compounds are effective as catalysts for carbenoid reactions of diazo compounds (1-3). Their catalytic activity depends on coordination unsaturation at their metal center which allows them to react as electrophiles with diazo compounds. Electrophilic addition to diazo compounds, which is the rate limiting step, causes the loss of dinitrogen and production of a metal stabilized carbene. Transfer of the electrophilic carbene to an electron rich substrate (S ) in a subsequent fast step completes the catalytic cycle (Scheme I). Lewis bases (B ) such as nitriles compete with the diazo compound for the coordinatively unsaturated metal center and are effective inhibitors of catalytic activity. Although carbene complexes with catalytically active transition metal compounds have not been observed as yet, sufficient indirect evidence from reactivity and selectivity correlations with stable metal carbenes (4,5) exist to justify their involvement in catalytic transformations. 

Compared to diazonium salts, diazo compounds are generally much less reactive towards nucleophiles than towards electrophiles. As a result of this azo coupling reactions of diazo compounds are the exception rather than the rule. Electron withdrawing substituents on the diazo carbon increase the reactivity towards nucleophiles. Consequently the ability to undergo azo coupling reactions increases from diazomethane to diazocarbonyl- and 2-diazo-l, 3-dicarbonyl compounds. Among the earliest reactions known were those with cyanide and sulfite ions Tertiary phosphines, as opposed to amines, can form stable addition complexes with diazoalkanes probably due to the ability of phosphorus to stabilize the betaine with its empty d orbitals (6). 

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... 

CRI Reaction of Diazo Compound 17a In our first attempts to perform the CRI reaction, the diazo compotmd 17a was treated with 1% CuOTf in freshly dried and degassed CH2CI2 tmder an N2 environment. To our delight, diazo decomposition of 17a proceeded smoothly at room temperature to yield the desired cyclopropyl intermediate 18a as a mixture of inseparable isomers (5.5 1) in 58% yield after 1 h the C-C insertion by-product 19 was also generated in 21% yield. The stability of 18a may reflect the lower ring strain in the 3/6 bicyclic ring system compared to that of... 

The rate of acid generation from BTf was larger than that of diphenyliodonium triflate(ITf). Deprotection of poly(tert-butyloxycarbonyloxystyrene) (tBOCHS) with BTf was 3 times faster than that with ITf after postexposure bake at same temperature. BTf with higher sensitivity and thermal stability may be expected to be PAG of diazo compounds applicable to microlithography resists. 

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