Diazoalkanes with acids

Because the rate-determining step for the reaction of diazoalkanes with acids varies from substrate to substrate and with reaction conditions, the discussion of rate- and product-determining steps cannot be wholly separated. The steps involving and following the loss of nitrogen will now be considered. The reason for making a division at this point is that diazonium ions are formed in a number of reactions and, to understand their behaviour, it is helpful to consider information from various sources. A considerable part of this section will, therefore, be devoted to reactions other than those of diazoalkanes themselves. 

The reaction is especially suited to the generation of optically active diazonium ions with specifically oriented counter-ions. In this respect it has possibilities which are absent for the reaction of diazoalkanes with acids and the deamination of aliphatic amines. However, in carrying out stereochemical studies, great care must be exercised to avoid spurious results, since the transient formation of a diazoalkane, either by loss of a proton from the diazonium ion or by what is probably a concerted elimination reaction of the diazoester, can lead to racemisation of the alkyl function and loss of asymmetry in the anion. Moreover, the diazoester is liable to nucleophilic displacement, for example by an acid molecule formed from already rearranged nitrosoamide, and this can lead to inverted product. 

The neutralizing effect of hydrogen ions upon ion pairs was originally suggested by Day and Whiting (1967) in connection with the photolysis of certain types of pyrazolenine esters. While the reactions of pyrazole-nines are not as well imderstood as the rearrangement of nitrosoamides or the reaction of diazoalkanes with acids, their mechanism is difficult to... 

The first step in the decomposition of nitrosoamides 123) is formation of the diazo ester 125) which fragments to a diazonium ion pair (128)129 The ion pairs thus produced differ from those obtained in the reaction of diazoalkanes with acids. The ratio of ester to ether formed in the decomposition of rV-nitroso-fV-benzhydrylbenz-amides in alcohol is lower than that found in the reaction of diphenyldiazomethane 132) with acids, and in the solvolysis of benzhydryl benzoate (I35)135,136 This effect has been attributed to the intervention of trans-diazo ester in the decomposition of 125) which leads to a greater distance between carbocation and carbox-ylate anion. In the diazoalkane reaction attack of the acid occurs at the electron-rich carbon atom to generate the carboxylate in the immediate vicinity of the incipient carbocation. 

Diazoalkanes alkylate acidic and enolic groups rapidly and other groups with replaceable hydrogens slowly. Carboxylic and sulfonic acids, phenols and enols are alkylated virtually instantaneously when treated with this reagent. Lewis acid catalysts (e.g., BF3.Et20) are used to promote the reaction of... 

F5TeO(CH2)2OTeF5, cis-[0(CH2)20]TeF4, and related compounds are formed in reactions of TeF with ethylene glycol and other polyhydric alcohols (69). The alkoxotellurium(VI) fluorides isolated so far are distillable liquids with considerable stability against hydrolysis. Some of these compounds have been prepared more easily by reacting diazoalkanes with pentafluoroorthotelluric acid (174), as in Eq. (11) ... 

Hydrazido(2-) and hydrazido(l-) complexes have also been shown to condense with aldehydes and ketones to give diazoalkane complexes containing the W=N—N=CRiR2 unit.387,388 Treatment of these complexes with LiAlFL, gives secondary amines and ammonia, whereas treatment with acid produces hydrazine, keto azines and N2-free tungsten compounds. Amines can also be produced from organohydrazido(2—) complexes.389,390... 

The O-alkylation of carboxylates is a useful alternative to the acid-catalyzed esterification of carboxylic acids with alcohols. Carboxylates are weak, hard nucleophiles which are alkylated quickly by carbocations and by highly reactive, carbocation-like electrophiles (e.g. trityl or some benzhydryl halides). Suitable procedures include treatment of carboxylic acids with alcohols under the conditions of the Mitsunobu reaction [122], or with diazoalkanes. With soft electrophiles, such as alkyl iodides, alkylation of carboxylic acid salts proceeds more slowly, but in polar aprotic solvents, such as DMF, or with non-coordinating cations acceptable rates can still be achieved. Alkylating agents with a high tendency to O-alkylate carboxylates include a-halo ketones [42], dimethyl sulfate [100,123], and benzyl halides (Scheme 6.31). 

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). 

In addition to the unsubstituted sulfene itself, the various substituted sulfenes used in the preparation of thietane 1,1-dioxides are listed in Table 4. Although the usual method for generating the sulfenes is by treatment of a methanesulfonyl chloride with triethylamine, sulfenes have been obtained by the reaction of phenyl-methanesulfonyl fluoride with phenyllithium, by treatment of a-chloro-ethanesulfinic acid with refluxing triethylamine,by treatment of 4-nitro-phenyl or 2-chloro-4-nitrophenyl, esters of arylmethanesulfonic acids with potassium t-butoxide or 2,6-dimethylpyridine, respectively, by treatment of diazoalkanes with sulfur dioxide" (e.g., to give 146) and by thermolysis of a Diels-Alder adduct of sulfene." ... 

The reactions of diazoalkanes and imines occur in generally low yields, but Lewis acid catalysis is of some help (equation 40). The reaction involves a 1,3-dipolar mechanism which proceeds through an isolable triazoline intermediate (Scheme 21). Treatment of the latter with acid affords aziridine in modest yield. 

Clearly DDM and diazoacetic ester are relatively stable diazoalkanes, and quite probably they differ little in stability from each other. The difference in rate-determining step in their reactions with acids can, therefore, be ascribed mainly to differences in the stability of the car-bonium ion intermediates. In the DDM reaction, the benzhydryl cation is of sufficient stability for loss of nitrogen from the diazonium ion to be more rapid than loss of a proton. For diazoacetic ester, on the other hand, 12... 

One model for bonding in a diazo compound would be die ylide (89 equation 37)." Unlike many other ylides, diazoalkanes are stable to air and water. With acid, however, protonation can lead to the highly reactive salt (90), the functional equivalent of the corresponding carbocation. As the substituents on the diazo group are made increasingly electron withdrawing, the ylide becomes less basic, and thus more stable to acid. Reaction of a diazo compound with a transition metal can also often be understood as proceeding via initial donation of electron density by (89) to a coordinatively unsaturated metal center. 

Reaction conditions for the acylation of higher diazoalkanes by acid chlorides are more critical. Since azo coupling of the diazo ketone with the diazoalkane can occur to give azines (equation 5), it is essential to avoid an excess of the diazoalkane and to carry out the acylation at lower temperatures. Typically, the acid chloride (1 equiv.) in ether is added to a stirred solution of the diazoalkane (1 equiv.) and triethylamine (1 equiv.) in ether at -40 C. Yields of the diazoketones are then ca. 74-91 %, and equation (6) is fairly representative. ... 

Three-membered heterocycles. Decomposition of diazo compounds by the iron complex in the presence of imines leads to aziridines. An analogous reaction of diazoalkanes with aldehydes gives some epoxides and the rearrangement products (ketones) owing to the Lewis acidic nature of the catalyst. Ethyl diazoacetate behaves differently, as 1,2-aryl shift occurs during the reaction. ... 

Diazirines are structural isomers of diazoalkanes. They are gases or colourless liquids, e.g. 3,3-dimethyldiazirine, bp 21°C. Liquid 3//-diazirines can decompose explosively. Their basicity is very low. Unlike diazoalkanes, they react with acids only slowly, with the liberation of nitrogen. 

All these fairly similar results are, however, in sharp contrast to solvolysis of cyclopropylmethyl chloride, which is much more reactive than cyclobutyl chloride or 4-chlorobut-2-ene (Roberts and Mazur, 1951 a). There was also positive evidence for internal return in the cyclopropylmethyl chloride solvolysis, although the solvent used (50 aqueous ethanol) is known to be unfavorable for internal return. Another reaction, closely related to the protolysis of cyclopropyldiazomethane mentioned above, is the reaction of that diazoalkane with ethereal benzoic acid. The product ratio cyclopropylmethanol cyclobutanol = 5.8 indicated a strong decrease of skeletal rearrangement (Moss and Shulman, 1968). 

A reaction that does work with simple diazoalkanes is the acylation with acid chlorides. This synthesis of diazo ketones was found by Staudinger et al. (1916 b), but its broad applicability and the optimization of the reaction conditions is mainly due to the work of Arndt and Eistert (Arndt et al., 1927 Arndt and Amende, 1928). Eistert proposed mechanism 9-6 for this reaction in 1935 and it was corroborated later in many respects. 

Various Reactions of Monocyclic Thiophens.—In connection with attempts to obtain a better synthesis of 3-thienylmalonic acid, the reaction of diazoalkanes with thiophen has been investigated. However, dimethyl diazomalonate gave the stable ylide (105). Simple diazo-ketones, on the other hand, resulted in... 

Alkylation of the Uthium salt of TMSCHN2 (TMSC(Li)N2) gives a -trimethylsLlyl diazoalkanes which are useful for the preparation of vinylsilanes and acylsilanes. Decomposition of a-tri-methylsilyl diazoalkanes in the presence of a catalytic amount of Copper(I) Chloride gives mainly ( )-vinylsilanes (eq 12), while replacement of CuCl with rhodium(II) pivalate affords (Z)-vinylsilanes as the major products (eq 12). Oxidation of a-trimethylsilyl diazoalkanes with m-Chloroperbenzoic Acid in a two-phase system of benzene and phosphate buffer (pH 7.6) affords acylsilanes (a-keto silanes) (eq 12). ... 

The metallocarbene intermediates are most often formed from thermal, photolytic, or metal-catalyzed deconposition of diazocarbonyl compounds, with concomitant loss of dinitrogen. Under transition metal catalysis, the initially formed species is a metallocarbene rather than a free carbene, and this is usually desirable due to the moderated reactivity (and, hence, fewer undesired side reactions) of the metal-complexed carbene. The two most common methods for introduction of the diazo group are acylation of diazoalkanes with suitably activated carboxylic acid derivatives and diazo transfer reactions in the case of more acidic active methylene substrates fScheme 16.12T... 

N,Ar-Dialkyl-4-diazomethylsulphonaniides (54) are new solid diazoalkanes with excellent storage properties, but possess similar reactivity towards acidic substances as normal diazoalkanes (Scheme 52). 

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