Oxazolidines, isomerization

The previous sections have dealt with stable C=N-I- functionality in aromatic rings as simple salts. Another class of iminium salt reactions can be found where the iminium salt is only an intermediate. The purpose of this section is to point out these reactions even though they do not show any striking differences in their reactivity from stable iminium salts. Such intermediates arise from a-chloroamines (133-135), isomerization of oxazolidines (136), reduction of a-aminoketones by the Clemmensen method (137-139), reductive alkylation by the Leuckart-Wallach (140-141) or Clarke-Eschweiler reaction (142), mercuric acetate oxidation of amines (46,93), and in reactions such as ketene with enamines (143). 

Oxidation of oxazolidine derivatives (275) gives isomeric pairs (A) and (B) of a-methoxy-substituted oxazolidine nitroxyl radicals (276a-d, f, g) and a,a-dimethoxy-substituted nitroxyl radical (276e) (Scheme 2.102) (515). 

Formaldonitrone, CH2=N(H)—O (3), the elusive simplest organic nitrone, has been prepared transiently in the gas phase by femtosecond collisional neutralization of its cation radical, CH2—N(H)—0+". The latter was generated by dissociative ionization of 1,2-oxazolidine. Nitrone 3 showed negligible dissociation upon collisional neutralization and was distinguished from its tautomers formaldoxime 2 and nitrosomethane 1 that gave different NR mass spectra. The enthalpy of formation was calculated from enthalpies of atomization and two isodesmic reactions as Af//29s(3) = 58 1 kJmol . The calculated, large activation barriers for isomerization of 3 (179 and 212 kJmoH for 3 anti-2 and 3 1, respectivelyindicate that once 3 is formed and diluted in the gas phase it should not isomerize unimolecularly to either 1 or (syn/anti) 2. 

The Pd-catalyzed reaction of 5-vinyl-l,3-oxazolidin-2-ones 260 at 65-70°C and 65 atm of CO in ethanol gave 5-lactams 263 in fairly good to high yields (Scheme 38).As Scheme 38 illustrates, this decarboxylative carbonylation reaction is likely to involve (i) the cleavage of the allylic C-O bond of 260 to form tr-allyl-Pd complex syn-2(A, (ii) isomerization to anti-2(A, (iii) decarboxylation forming 7r-allyl-Pd-amine complex 262, and (iv) CO insertion to 262 followed by aminolysis to yield 5-lactam 263. 

Aliphatic aldehydes and ketones react with aziridines to form relatively stable half aminals, eg, aziridine reacts with formaldehyde to form Ai-hydroxymethylaziridine [20276-43-1]. Half aminals can be converted to full aminals by reaction with a further secondary amine, isomerized to oxazolidines by the action of heat or used in a Mannich reaction for the ring aminomethylation of phenols, although this reaction gives only moderate yields (218-227). 

Reaction of the carbohydrate-based cyclic sulfites with NaSCN was used for the synthesis of f -l, 2-liised oxazolidine-2-thiones (Table 4) <1995TL5347>. Seleno and oxo derivatives were obtained with KSeCN or NaOCN, respectively <2000MI397>. The stereochemistry of products can be explained by the intermediate isomerization of /3-thiocyanates into cr-isothiocyanates (Scheme 10) <1995TL5347, 2000MI397>. 

Arylcyclopropanes and their heterocyclic analogues are liable to electron transfer induced fragmentation of a carbon-carbon bond that in some cases leads to synthetically useful products. Thus, 1,2-diarylcyclopropanes [240-243] as well as 2,3-diaryloxirans [244-246] and -aziridines (in the last case, also 2-monophenyl derivatives) [247,248] are cleaved upon photoinduced electron transfer sensitization. The final result, after back electron transfer, is trans-cis isomerization of the ring. In the presence of a suitable trap, however, a cycloaddition reaction takes place, involving either the radical cation or the ylide. Thus, dioxoles, ozonides or azodioxoles, respectively, are formed in the presence of oxygen and oxazolidines have been obtained from cyclopropanes in the presence of nitrogen oxide (Sch. 23). 

Similarly, N-trimethylsilyl-N -phenylcarbodiimide 281 reacts with aldehydes in the presence of fluoride ions to give the isomeric 1,3-oxazolidines 282 and 283. ... 

Generation of azomethine ylides by starting from oxazoline heterocycles consists of the following steps (1) valence isomerization of 4-isoxazolines, (2) valence isomerization of 4-oxazolines, and (3) cycloreversion of 5-oxazo-lidinones or oxazolidines. These three generation methods as variations of the oxazoline route are reviewed in this section. 

In the end, the stereochemistry of the reacting dipole is determined by the relative rates of the reversible ring closure of the iminium carboxylate betaine into 2,4-trans-5-oxazolidines (kj), the decarboxylative ylide generation (kj), the isomerization of anti-ylides into syn-ylides (kj), and cycloaddition trappings 1(4 and kj), as shown in Eq. (23). 

The 1,3-dipolar cycloaddition of nitrones to olefins gives 1,2-oxazolidines. Because nitrones can undergo (Z)/( )-isomerization, diastereomers are formed, especially if the reaction is performed at elevated temperature (Scheme 10.16). In addition, 1,3-dipolar cycloadditions of nitrones to olefins may proceed via endo- or exo-transition states [41]. 

When CLXVIII was heated under reflux with methanol-d for 24 hours, conditions sufficient to isomerize atisine, no deuterium was incorporated in the product, which was identical with starting material. Refluxing with added NaOD for 3 hours resulted in less than 5% incorporation. Refluxing in a mixture of dioxane and deuterium oxide at 85° for 24 hours resulted in < 30% incorporation of one deuterium atom per molecule. Thus it is evident that without the steric driving force which is present in the alkaloid system, strenuous conditions are required to effect isomerization (54). In another model system of the arylaralkyl oxazolidine type (CLXXII and CLXXIII), in which there was no steric differentiation between the two a-W-carbons, but in which the protons on these particular carbons were relatively more acidic than in the diterpene... 

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