Diazo compounds amides

Amides can also be alkylated with diazo compounds, as in 10-49. Salts of sulfonamides (ArS02NH ) can be used to attack alkyl halides to prepare N-alkyl sulfonamides (ArS02NHR) that can be further alkylated to ArS02NRR. Hydrolysis of the latter is a good method for the preparation of secondary amines. Secondary amines can also be made by crown ether assisted alkylation of F3CCONHR (R = alkyl or aryl) and hydrolysis of the resulting F3CCONRR. ... 

More recently, Williams has described the one pot synthesis of 2-substituted oxazoles 11 by the thermolysis of triazole amides 9 the reaction does not proceed photo-chemically.<92TL1033> Although the reaction does not involve addition to a nitrile, it is an interesting application of a diazo compound since the proposed zwitterionic intermediate 10 is a resonance form of a diazo imine, so formally the reaction may be thought of as a thermal decomposition of a diazo imine (Scheme 6). 

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. 

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]. 

The second class of benzo-fused heterocycles accessible from benzofuroxans are benzimidazole oxides. In this case only one carbon from the co-reactant is incorporated in the product. With primary nitroalkanes 2-substituted l-hydroxybenzimidazole-3-oxides (46) are formed via displacement of nitrite, and / -sulfones behave similarly. The nitrile group of a-cyanoacetamides is likewise eliminated to alford 2-amide derivatives (46 R = CONRjX and the corresponding esters are formed in addition to the expected quinoxaline dioxides from acetoacetate esters. Under similar conditions secondary nitroalkyl compounds afford 2,2-disubstituted 2//-benzimidazole-1,3-dioxides (47). Benzimidazoles can also result from reaction of benzofuroxans with phosphorus ylides <86T3631>, nitrones (85H(23)1625>, and diazo compounds <75TL3577>. 

The modification of carboxyl groups has been carried out (1) by esterification with dry methanol and HC1, (2) by esterification with aliphatic diazo compounds, (3) by the formation of adducts with carbodi-imides, or (4) by the formation of amides through activation with carbodiimides. Both complete and, apparently specific, partial modification of the 11 free carboxyl groups have been obtained. In general, the first method suffers from the denaturing medium, the second from incomplete reaction, and the third from the uncertain nature of the products. The fourth procedure is perhaps subject to the least question. There are a total of 11 free carboxyl groups in native RNase-A l (Val), 5/ (Asp), 5y(Glu). A summary of the derivatives is given in Table V. 

A vast array of chiral catalysts have been developed for the enantioselective reactions of diazo compounds but the majority has been applied to asymmetric cyclopropanations of alkyl diazoacetates [2]. Prominent catalysts for asymmetric intermolecular C-H insertions are the dirhodium tetraprolinate catalysts, Rh2(S-TBSP)4 (la) and Rh2(S-DOSP)4 (lb), and the bridged analogue Rh2(S-biDOSP)2 (2) [7] (Fig. 1). A related prolinate catalyst is the amide 3 [8]. Another catalyst that has been occasionally used in intermolecular C-H activations is Rh2(S-MEPY)4 (4) [9], The most notable catalysts that have been used in enantioselective ylide transformations are the valine derivative, Rh2(S-BPTV)4 (5) [10], and the binaphthylphosphate catalysts, Rh2(R-BNP)4 (6a) and Rh2(R-DDNP)4 (6b) [11]. All of the catalysts tend to be very active in the decomposition of diazo compounds and generally, carbenoid reactions are conducted with 1 mol % or less of catalyst loading [1-3]. 

In reaction 12-10, treatment of Z-CH2-Z with tosyl azide gave the a-diazo compound via diazo transfer. When this reaction is performed on a compound with a single Z group such as an amide, formation of the azide becomes a competing process... 

Sodium amide can reduce the nitre group of aromatic nitro compounds to give a small yield of diazo compounds (161 > 162]. 

A variety of monoanionic N,0-chelate complexes have been described. These include ligands derived from phenolic diazo compounds, a variety of Schiff-base derivatives, aldehyde hydrazone ligands,762 thiazolidin-4-ones,763,764 and salicylideneamino-3,5-dimercapto-l,2,4-tri-azoles.760 Similarly, the complexes Ti(OPr )4 (NHC(0)R) (R = Me, Ph, NC5H4, n 4) are thought to be coordinated via the carbonyl group of the amide functional group.765... 

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