Nitrones, synthesis rearrangements

Namitharan, K. and Pitchumani, K. 2011. Copper(l)-catalyzed three component reaction of sulfonyl azide, alkyne, and nitrone cycloaddition/rearrangement cascades A novel one-step synthesis of imidazolidin-4-ones. Org. Lett. 13(21) 5728-5731. 

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... 

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>. 

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). 

Evidently, this approach is not limited to the formation of nitronates, nitroso acetals or enoximes. The rearrangements of these compounds by elimination reactions, the trapping of intermediates and finally their reactions with various reagents are of equal importance. It should be emphasized that silylation of AN as a process in organic chemistry is characterized by an unrivalled completeness and diversity of transformations. Hence, the silylation can be considered as a separate field of application of AN in organic synthesis. 

A novel route to the azepinone system in 93 and 94, based on an intramolecular nitrone-eneallene cycloaddition (in 91 and 92, which were accessed in turn from 88 via 89 and 90) and subsequent rearrangement via N-O bond homolysis and an electrocyclic recyclization step) has been described (Scheme 11) <2005EJ02715>. On heating 93 in toluene, equilibrium with the isomeric azepinone 95 was established, although comprising less than 3% of 95. The general synthetic approach was applied to the synthesis of an analogue of the alkaloid astrocasine. 

The reported synthesis and properties of an oxaziridine by the thermal isomerization of the C7-trityl ester of 3-ac/nitrocamphor bears reinvestigation, particularly in view of the recent report that irradiation of nitronate salts yields hydrox-amic acids but that oxaziridine intermediates could not be detected.) A -Sulfonyl-oxaziridines also rearrange, thermally to nitrones that further decompose to products, but photochemically they yield amides. ... 

Using this methodology, the first total synthesis of the natural product (-)-(19R)-ibogamin-19-ol was reported [106]. The crucial ISQ core containing the entire configurational stereochemistry of the final target compound was prepared in 15 steps. The two key steps involved chirality transfer in an Ireland-Claisen rearrangement and an intramolecular nitrone-olefin 1,3-dipolar cycloaddition described earlier. 

A -Pyrroline-A xides (nitrones) derived finm tartaric acids feature in several syntheses of 132 and ent- 32. The first of two routes by Brandi and co-workers commenced with a dipolar cycloaddition between the nitrone 142 (R = tert-butyldiphenylsilyl, or TBDPS) and methylenecyclopropane (143), which afforded a mixture of spirocyclopropylisoxazolidine 144 and its bridgehead epimer (10 1) (Scheme 20, top line) (5i). When heated in xylene, 144 rearranged cleanly to enaminone 145 and the indolizidinone 146, the latter undergoing ready conversion via the tosylhydrazone into the target diol, ( + )-132. A subsequent synthesis with... 

In general, synthesis of 4-isoxazolines is accomplished via three routes 1,3-dipolar cycloaddition of nitrones to alkynes or by the oximation of a,i -ethylenic ketones, a-alkynic ketones and aldehydes or from the selective reduction of isoxazolium salts. The nitrone (262) underwent tandem cyclo-addition-[2,3]sigmatropic rearrangement with allenyl sulfoxide (263). And it resulted in 4-isoxazoline (264) (Equation (46)) <89TL663>. 

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