Huisgen rearrangement

An unusual Schmidt reaction has been observed with ketone (56) <95H(40)223>. When the reaction is carried out using hydroxylamine 0-sulfonic acid/formic acid, the expected ring expansion to the tetrahydropyridinones occurs. With hydrazoic acid, however, the unexpected 1,3-diazepine system is obtained (58). This observation is rationalized by the intermediate (57), formed by addition of hydrazoic acid to the initially formed lactam, which then undergoes a Huisgen rearrangement. 

It was found that addition of excess of benzoyl chloride in the absent of base provided 1,3,4-oxadiazoles 8-10 (R = CH2CI, CH2COOEt, CH2N3, respectively) in good yields. These substrates are not tolerated when pyridine was used as under the original Huisgen rearrangement conditions. 

Investigations of the constitution and the configuration at the azo groups in diazoanhydrides are difficult because they decompose very rapidly if dissolved in organic solvents, and their water solubility is not sufficient. The results obtained by Kauffmann et al. using HCN in water are in favor of the covalent structure 6.13 rather than of a diazonium-diazoate salt they obtained (in 93% yield) two equivalents of (Z)-4-chlorobenzenediazocyanide. In ethanol the products shown in Scheme 6-8 were obtained, i.e., the same products as obtained by Huisgen and Nakaten (1951, 1954) under similar conditions from (Zi)-diazoacetate, the intermediate in the intramolecular rearrangement of AT-nitrosoacetanilide. 

The reaction of 1,2,3-triazolium-l-aminides 3 with propiolate esters led to fluorescent 2,5-dihydro-1,2,3-triazine derivatives 4 in one pot, involving a Huisgen cycloaddition followed by a sequence of rearrangements <06JOC5679 06TL1721>. These reactions can be carried out in acetone, in water, or under solvent-free conditions. 

During the synthesis of 436, Muraoka and colleagues produced the diazobi-cyclo[4.3.1]decane 435 via the classical ring expansion (equation 184). Huisgen-White rearrangement of the cyclic lactam leads to 436, a key synthetic intermediate for piperidine alkaloids. 

Although it has been established that the HOMO (diazoalkane)-LUMO (alkene) controlled concerted cycloaddition occurs without intervention of any intermediate for the reactions of simple diazoalkanes with alkenes, Huisgen once proposed a mechanistic alternative 4 namely an initial hypothetical nitrene-type 1,1-cycloaddition reaction of phenyldiazomethane to styrene followed by a vinylcyclopropane-cy-clopentene-type 1,3-sigmatropic rearrangement Control experiments, however, excluded this hypothesis for the bimolecular 1,3-dipolar cycloaddition reaction of diazomethane (Scheme 60).204... 

The iron-catalyzed [3 + 2]-cycloaddition (Huisgen reaction) of nitriles and carbonyl compounds as reported by Itoh et al. is one of the rare examples reported where an iron reagent can be utilized for the synthesis of 1,2,4-oxadiazoles (Scheme 9.35) [93]. In this reaction, methyl ketones are nitrated at the a-position by Fe(N03)3 to generate an a-nitro ketone. This intermediate rearranges to an acyl cyanate, which reacts further with the nitrile to give the heterocyclic product 48 in good to excellent yields (R1 = Ph, R2 = CH3 95% yield). 

The platinum-catalysed intramolecular domino annulation reaction of o-alkynylben-zaldehydes has been described as a versatile approach to naphthalenes with annulated carbocycles or heterocycles of various sizes (Scheme 32).94 A plausible mechanism for the platinum(II)-catalysed annulation reaction shows that the double annulation process most probably proceeds through the benzopyrylium cation (117), which results from the nucleophilic attack of the carbonyl oxygen at the alkyne, activated by the Lewis-acidic platinum salt. A subsequent intramolecular Huisgen-type 3 + 2-cycloaddition of the second alkyne is assumed to generate intermediate (118). Rearrangement to (119) and the formal 4 + 2-cycloaddition product (118) leads to the aromatized final (116), liberating the active catalyst. In the case of FeCl3 as the Lewis acid, we assume that intermediate (118) is oxidatively transformed to (121). 

The rearrangement of N-alkyl-N-nitrosoamides has contributed much to the delineation of scheme 5. The reaction has been shown to proceed with the formation of a diazoester intermediate which fragments to a diazonium ion pair as shown below (White, 1955 White and Aufder-marsh, 1961b Huisgen and Reimlinger, 1956a and b). 

It is possible that similar behaviour is responsible for the rather surprising finding that the product obtained from reaction of the carbonium ion with solvent in the rearrangement of nitrosoamides in aqueous or ethanolic solution is also of retained configuration (Huisgen and Riichardt, 1956b White and Elliger, 1967). 

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