1-Pyrroline 1-oxides, reaction with

Anionic/oxidative reaction sequences have been developed in addition to the domino anionic/reductive processes. For example, with regard to the synthesis of novel diaryl heterocycles as COX-2 inhibitors [500], including rofecoxib (Vioxx) 2-972 [501] (which has recently been withdrawn from the market) or the pyrrolin-2-one derivative 2-973 [494], Pal and coworkers reported on a so-far unique domino aldol condensation/oxidation sequence (Scheme 2.218) [503]. 

Cyclic imidate esters, 2-ethoxypyrrolin-5-one and 2-ethoxy-1II -indol-3-one, undergo 1,3-dipolar cycloaddition reactions with nitrile oxides, the reaction site being at the pyrroline C=N bond (317). Rigid and sterically congested pyrroline spiro compounds 148 demonstrate complete diastereofacial selection in site and regiospecific cycloaddition reactions with nitrile oxides to give products 149 (318). 

In this type of spin traps, 5,5-dimethyl-l-pyrroline-Af-oxide (DMPO) deserves particular mention. DMPO is widely employed as a spin trap in the detection of transient radicals or ion-radicals in chemical and biological systems (see, e.g., Siraki et al. 2007). Characteristic ESR spectra arising from the formation of spin adducts are used for identification of specific spin species. In common opinion, such identification is unambiguous. However, in reactions with superoxide ion (Villamena et al. 2004, 2007b), carbon dioxide anion-radical (Villamena et al. 2006), or carbonate anion-radical (Villamena et al. 2007a), this spin trap gives rise to two adducts. Let us consider the case of carbonate anion-radical. The first trapped product arises from direct addition of carbonate anion-radical, second adduct arises from partial decarboxylation of the first one. Scheme 4.25 illustrates such reactions based on the example of carbonate anion-radical. 

Another possible route to thienamycin (487) has utilized the dipolar cycloaddition of 1-pyrroline 1-oxide (482) with methyl crotonate (79TL4359). The reaction is highly stereoselective due to the operation of secondary orbital effects. The isoxazolidine (483), produced in 90% yield, was subjected to hydrogenolysis, and the resulting amino alcohol (484) was selectively blocked with hexamethyldisilazane to give (485). Treatment with ethylmagnesium bromide then gave /3-lactam (486 Scheme 107). 

The polymeric pyrrolic autoxidation products probably result from the oxidized monomeric systems, which are analogous in structure to those isolated from photooxidation and peroxide oxidation reactions. Thus, for example, analysis of the products of the autoxidation of 1-methylpyrrole (Scheme 47) would suggest that 1 -methyl-A3-pyrrolin-2-one (153) is initially formed from a radical reaction of the pyrrole with triplet oxygen. This reaction sequence should be compared with that proposed for the oxidation of pyrroles with hydrogen peroxide (Scheme 50), which yields (181), (182) and (183) as the major isolable products. The acid-catalyzed reaction of a pyrrole with its oxidation product e.g. 153) also results in the formation of polymeric material and the formation of pyrrole black is probably a combination of oxidation and acid-catalyzed polymerization processes. 

The A pyrroline-A-oxides (SO) undergo violently exothermic reactions with DM AD in the absence of solvent.95 In ether at room temperature, unstable products (51) that rearrange exothermically to the pyrrolines (52) are formed this ring fission recalls that of isoxazolium salts.96 With unsymmetrical acetylenes, two modes of cycloaddition are possible. Propiolic acid adds to 50 (R = H), giving an unstable solid... 

The N-oxides of special position, although their reactions with nucleophilic reagents are similar to the reactions of other imines. These compounds have been studied particularly in connection with attempts to synthesize the cyclic skeleton corrin of vitamin B12. 

Achiwa reported a short synthesis of pyrrolizidine derivatives by the cycloadditions using a nonstabilized azomethine ylide 23 (m = 1) (82CPB3167). When the trimer of 1-pyrroline is treated with a silylmethyl triflate, N-alkylation of the 1-pyrroline takes place. Then the resulting iminium salt is desilylated with fluoride ion in the presence of ethyl acrylate to give ethyl pyrrolizidine-l-carboxylate 295 as a mixture of stereoisomers (28%). After the epimerization of 295 with LDA, the ester moiety is reduced with lithium aluminum hydride in ether to provide (+ )-trachelanthamidine (296). A double bond can be introduced into 295 by a sequence of phenyl-selenylation at the 1-position, oxidation with hydrogen peroxide, and elimination of the selenyl moiety. The 1,2-dehydropyrrolizidine-l-carboxylate 297 is an excellent precursor of (+ )-supinidine (298) and (+)-isoretronecanol (299). Though in poor yield, 297 is directly available by the reaction of 23 with ethyl 3-chloropropenoate. 

Pyrrolines 107 can also afford the oxazabicyclohexanes 106 on oxidation with hydrogen peroxide, or more commonly with peracids. " Both the photorearrangement and the oxidation reactions are widely applicable. 

The effect of substituents and reaction conditions on the reaction of pyrroline iV-oxides (115) with phosphonate anions has been discussed. > ... 

Proline. Proline catabolism begins with an oxidation reaction that produces A -pyrroline. The latter molecule is converted to glutamate-y-semialdehyde by a hydration reaction. Glutamate is then formed by another oxidation reaction. 

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