Rearrangements of nitrones

The cycloadducts formed from the Diels-Alder reaction of 3-amino-5-chloro-2(17/)-pyrazinones with methyl acrylate in toluene are subject to two alternative modes of ring transformation yielding either methyl 6-cyano-l,2-dihydro-2-oxo-4-pyridinecarboxylates or the corresponding 3-amino-6-cyano-l,2,5,6-tetrahydro-2-oxo-4-pyridinecarboxylates. From the latter compounds, 3-amino-2-pyridones can be generated through subsequent loss of HCN <96 JOC(61)304>. Synthesis of 3-spirocyclopropane-4-pyridone and furo[2,3-c]pyridine derivatives can be achieved by the thermal rearrangement of nitrone and nitrile oxide cycloadducts of bicyclopropylidene <96JCX (61)1665>. 

Rearrangements of nitrones due to migration of the A-oxide oxygen can be induced both, photochemically and by various reagents, but in specific conditions it can proceed spontaneously. On one hand, such transformations are caused by the O-nucleophilic character of nitrones able to react easily with acid anhydrides, their halo anhydrides, sulfonyl chloride and other agents on the other hand, by a significant CH-acidity of a-alkyl groups. 

Beckman rearrangement of nitrone (262) into amide (263) occurs in the reaction with lithium cyanide. However, this reaction gives lactam (264) instead of the expected 2-cyanopyrrolidine 1-oxide (265) (Scheme 2.96) (473). 

In continuation of our studies on the reactivities of nitrones 33, we report herein the solvent directed rearrangement of nitrones 33 to 34 and/or 31 and conversion of 5 (R = alkyl) to coumarino [3,4-d]-isoxazole. Nitrones 33 (R = alkyl) were prepared by reaction of 32 with nitroalkanes 35 and Zn in the presence of HOAc in EtOH under an inert atmosphere. Nitrones 33 Were... 

The photochemical rearrangement of nitrones to amides often involves initial formation of oxaziridine intermediates. These oxaziridines can be isolated in good to excellent yields (Table 31). 

There are a number of thermal and photochemical reactions for which oxaziridine intermediates have been proposed but never isolated. These include, among others, the photochemical Beckmann rearrangement of oximes, many photochemical reactions of aromatic A -oxides, and the thermal rearrangement of nitrones to amides. A brief discussion of the first two seems warranted in this review because they have been studied extensively and some strong inferential evidence for oxaziridine intermediates has been obtained. 

Although further examples of photochemically induced rearrangement of nitrones and /V-oxides have been described this year, little novelty can be attached to most of these reports. The N-oxide (76), on irradiation in the presence of a proton source such as persulphate or dilute sulphuric acid, is converted into the corresponding 4-aryl-2 -l,4-benzoxazin-3(4iZ>one (77) 5 evidence for the pathway outlined in Scheme 3 involving the oxaziridine (78) as an intermediate is presented. 

Vicinal N-alkylamino-alcohols were prepared by acylation-rearrangement of nitrones, followed by hydride reduction (Scheme 64).146... 

R- -> [(CF3)2CF N 0-. R] ->F- + (CF8)aC N-0-R [R = (CFs)8C or Hi] (no radical intermediates were detected using e.s.r. and C3DNP techniques) the possibility remains that the oximes arise via Meisenheimer-type rearrangement of nitrones produced initially via straightforward nucleophilic attack on... 

Beckmann rearrangement of nitrones Lactams from cyclic nitrones Ring expansion... 

Rearrangement. The considerable number of reports associated with the photochemically induced rearrangement of nitrones, oximes, and oxaziridines reflects the continuing interest in this area. The ratio of caprolactam to hexanoamide formed from irradiation of the oxaziridine (659 R = H) was different from that obtained by irradiation of cyclohexanone oxime. Photo-... 

A" -Isoxazolines, which are readily accessible by 1,3-dipolar addition of nitrones and nitronic esters to activated alkynes, undergo facile rearrangement upon warming (<110 °C)... 

Pertluoroallene is also quite reactive in its additions to nitrones [20], diazoalkanes [20] and sydnones [19] With sydnones, the isolated product derives from a fluoride ion rearrangement of the primary adduct (equation 21)... 

The light sensitivity of nitrones in solution was observed by Kamlet and Kaplan, " who postulated the formation of oxaziranes. Krohnke formulated the rearrangement caused by light on a nitrone by using an oxazirane as an intermediate. Splitter and Calvin successfully isolated the rearranged products (9, 11, 12) and identified them as known oxaziranes [Eq. (6)]. 

The rearrangement of phenyl- er -butyl nitrone to the isomeric oxazirane (9) occurred in 95% yield on irradiation in acetonitrile for 2 hr. Because 2-ieri-butyl-3-phenyloxazirane (9) can be reconverted into the more stable nitrone, the photochemical reaction involves the conversion of radiation energy into chemical energy. 

The rearrangement of 2-fert-butyl-3-phenyloxazirane to the isomeric nitrone is quantitative on refluxing 3 days in acetonitrile [Eq. (25)]. ... 

Continuing his studies on the metallation of tetrahydro-2-benzazepine formamidines, Meyers has now shown that the previously unsuccessful deprotonation of 1-alkyl derivatives can be achieved with sec-butyllithium at -40 °C <96H(42)475>. In this way 1,1-dialkylated derivatives are now accessible. The preparation of 3//-benzazepines by chemical oxidation of 2,5- and 2,3-dihydro-l/f-l-benzazepines has been reported <96T4423>. 3Af-Diazepines are also formed by rearrangement of the 5//-tautomers which had been previously reported to be the products of electrochemical oxidation of 2,5-dihydro-lAf-l-benzazepine <95T9611>. The synthesis and radical trapping activities of a number of benzazepine derived nitrones have been reported <96T6519, 96JBC3097>. 

Hydroxylated nitrones 321 and 322 afford, by subsequent thermal rearrangement of the adducts, a straightforward approach to polyhydroxylated indolizidines, inhibitors of glycosidases. The total synthesis of (+ )-Len-tiginosine is representative of the process (Scheme 47) [82]. 

Oxidation oflmines Oxidation of imines with peracids leads to oxazi-ridines, with the possibility of their successive rearrangement into nitrones, depending on their structure and the employed oxidant. 

The use of m-CPBA allows the formation of nitrones in the oxidation of tertiary amines. The resulting amines A-oxides are subject to either Cope or Meisenheimer rearrangements, providing formation of nitrones. Thus, the generated corresponding nitrones in the oxidation of bicyclic aziridines give nitrones as a result of a Meisenheimer rearrangement (Scheme 2.14) (93). 

For the first time, the primary nitrone (formaldonitrone) generation and the comparative quantum chemical analysis of its relative stability by comparison with isomers (formaldoxime, nitrosomethane and oxaziridine) has been described (357). Both, experimental and theoretical data clearly show that the formal-donitrones, formed in the course of collision by electronic transfer, can hardly be molecularly isomerized into other [C,H3,N,0] molecules. Methods of quantum chemistry and molecular dynamics have made it possible to study the reactions of nitrone rearrangement into amides through the formation of oxaziridines (358). 

Photochemical Rearrangement Isomerization of nitrones to oxaziri-dines is a general reaction of various cyclic and acyclic nitrones (447-449). When this reaction is reversible, many transformations of nitrone to oxaziridine and back to nitrone can be carried out without decomposition. This reaction is of special interest in view of light energy accumulation (450, 451). 

To illustrate the synthetic use of photochemical rearrangement, the photolysis of nitrones (249) leading to the formation of bicyclic lactams (250) is an example (Scheme 2.88) (459). 

An alternative method in the synthesis of alkaloids, photochemical rearrangement of endocyclic nitrones into bicyclic lactams has drawn special attention. Analyses of photochemical rearrangement and application of modified conditions of the Barton reaction testify to the comparability of results obtained in these approaches (Scheme 2.89) (460). 

Specific regularities of nitrone rearrangements have been studied under photoirradiation at various conditions (in solvent, in polymeric matrixes, and in films... 

It was demonstrated that treatment of nitronate Me02CH=N(0)0Me with HCI (246), as well as heating (298) affords oxime (104a) as a result of standard thermal decomposition of alkyl nitronates, which occurs via a Cope rearrangement (233) (Scheme 3.87). 

Rearrangements of Cyclic Nitronates Many rearrangements of cyclic nitronates occur under the action of LA and involve the interaction with the negative end of the dipole as the initial step. If an aryl substituent is bound to the C-4 atom, deep skeletal rearrangements, including annelation, are possible. Japanese researchers (321) systematically studied the reactions of a representative... 

Six-membered cyclic nitronates can undergo rearrangements accompanied by cleavage of the endocyclic N-0 bond or by cleavage of the endocyclic C-0 bond. The latter fact is evidently associated with the presence of substituents, which efficiently stabilize the positive charge, at the C-6 atom. This occurs upon treatment of nitronates (154a,b) with silicon dioxide (Scheme 3.123) (117). 

Similar tautomeric rearrangements of intermediate six-membered cyclic nitronates were described by Huffman and coworkers (116) (Scheme 3.124). 

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