Nitrones, rearrangement

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). 

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

Open chain iV-oxides, in particular nitrones, rearrange to amides (almost quantitatively) under acetic anhydride conditions (eq 39). ... 

Most other acylating agents act on salts of either primary or secondary nitroparaffins by O-acylation, giving first the nitronic anhydrides which rearrange to give, eg, nitrosoacyloxy compounds (28). 

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)... 

Rearrangement involving cleavage of the C—O bond is also observed with the phenyl isocyanate adduct (59). In place of an O-acylated nitrone its product (60) of acyl migration is isolated (67JPR(36)86). 

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)... 

Extensions of 1,3-dipolar additions of aromatic azides (720,721) to other enamines (636), and particularly to the enamine tautomer of SchilTs bases, were explored (722,723). Further nitrone additions were reported (724,725) and a double nitrile oxide added to an endiamine (647). Cyanogen azide and enamines gave cyanoamidines through rearrangement (726). 

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)]. ... 

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>. 

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>. 

An interesting strategy for the synthesis of pyrrolizidines and indolizidines has been developed by Brandi and co-workers. Cycloaddition between nitrones or nitrile oxides with methylenecyclopropanes generates strained tricyclic spiro compounds, which are prone toward further transformations, such as rearrangement, ring opening, and new ring closure (Scheme 10.17).116... 

Nitrones derived from 2-azabicyclo[5.3.0]decane give quinolizidine compounds by photochemical Beckmann rearrangement which implies simultaneous ring expansion and ring contraction reactions. Intramolecular Schmidt reactions in 2(4-azidobutyl)-cyclopentanones also give quinolizidinone derivatives by ring expansion. Examples of both types of reactions are given in Sections 12.01.11.1 and 12.01.11.3, respectively. 

The impulse to the study of these cycloadditions came from the discovery that 5-spirocyclopropane isoxazolidines (or isoxazolines) undergo a thermal rearrangement resulting in the production of selectively substituted tetrahydro-(or dihydro) pyrid-4-ones (Scheme 42) [64], In particular, cyclic nitrones gave ultimately N-bridgehead bicyclic ketones, molecular skeleton of many alkaloid families [65]. 

The major adduct from C,iV-diphenyl nitrone (265) and 1 could not be isolated, as the 5-spirocyclopropaneisoxazolidine 266 underwent rearrangement under the reaction conditions, also affording the uncommon rearrangement product benzazocine 269 (Scheme 43) [66],... 

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]. 

An intramolecular nitrone 1,3-dipolar cycloaddition reaction to give 46 from 45 followed by reductive N-O bond cleavage afforded a stereoselective synthesis of the tetrahydro 177-1-benzazepines 47 the nitrone precursors 44 were prepared in turn by a Claisen rearrangement from an IV-allylamine <06SL2275>. 

Spirocyclopropane isoxazolidines 75, obtained from alkylidenecyclopropane nitrones, underwent thermally induced selective rearrangement to pyrrolo[3,4-A]pyridinones 76 <00TA897>. The same adducts 75 in the presence of a protic acid afforded exclusively p-lactams 77 (57-60% yield) accompanied by ethylene extrusion <00JA8075>. 

The one step domino cycloaddition-rearrangement process of A-aryl nitrones 78 to BCP (79) afforded spirocyclopropane-annelated pyridones 81 and benzazocinones 82 in good overall isolated yields <00SL1034>. 

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. 

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