Nitrone cycloaddition ring-opening

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... 

Two protected 3-amino acids, containing indolizidine and quinolizidine skeletons (607a,b), have been synthesized by using 1,3-dipolar cycloaddition of nitrones (551) and (552) to methyl ( )-5-mesyloxy-2-pentenoate. The key steps of this approach is demonstrated by novel syntheses of indolizidinone and quino-lizidinone derivatives (606a,b) and by the ring opening of the tricyclic 1,3-dipolar cycloaddition products (605a,b) (Scheme 2.268) (779). 

The retro-1,3-dipolar cycloaddition of imidazo[l,5- ][l,2,4]oxadiazoles 40, promoted by reaction with triphenylphos-phine at reflux in THF, gives the cyclic nitrones 187 (unreported yields) (Equation 15) <1997T13873>. The ring opening of compounds 40 leading to heterocycles 187 (Equation 15) can also be achieved thermally in the condensed phase under vacuum <1997TL2299>. 

The nitrone of piperidine reacts with phenyl vinyl ether to yield a 1,3-dipolar cycloaddition product. Benzylation led to a ring-opened product which was converted to a hydroxamic acid. This is desired functionality in medicinal chemistry because it is a metal-binding ligand <03S1221>. 

The cycloadditions of nitrones with activated acetylenes provide 4-oxa-zolines, which readily ring open into highly stabilized azomethine ylides (Section II,H). This concept can be utilized in an intramolecular cycloaddition. Nitrones 277 undergo cycloadditions with dimethyl acetylenedi-carboxylate (OMAD) to give cycloadducts 278 through the formation of intermediary azomethine ylides (84CL797). It is quite surprising that the... 

Blechert et developed a multicomponent cascade reaction for the synthesis of indole derivatives as depicted in Scheme 1.8.5.17. The first step of the sequence involves formation of a nitrone derivative starting from phenylhydroxylamines and aldehydes. The resulting nitrones were not isolated but captured by a cyanoallene in a 1,3-dipolar cycloaddition reaction followed by hetero-Cope rearrangement, ring-opening and condensation to yield an indole derivative. 

In fight of the successful methodology used by Young and Kerr in the ability of activated cyclopropanes to undergo nucleophilic ring-opening/cycloaddition reactions with indoles and nitrones [21], Johnson and coworkers reported the synthesis of tetrahydrofurans via an adaptation of this... 

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