Nitrones open-chain

Simple oxaziridines and diaziridines do not absorb in the near UV. Lack of absorption was one argument to distinguish between true three-membered ring structures and unsaturated open chain isomers like nitrones or hydrazones. 

The three types of three-membered ring are also accessible by photoisomerization of open chain 1,3-dipoles nitrones, azomethinimines and linear diazo compounds respectively. All three-membered rings prepared prior to 1967 were included in a comprehensive review . 

The discussion of the structure of the nitrones and the hydrazones received less attention. With the increased application of physical methods to structural problems, the three-membered ring structures for these compounds lost much of their attraction. The problem of the structure of the nitrones was satisfactorily solved with the open-chain A -oxide formulation. The compounds originally designated as diaziridines (2) were partly reformulated with the open-chain hydra-zone structures and partly were left without a. satisfactory proof of structure. 

These experimental findings, as well as earlier data on alkylidenecyclopropanes, clearly disclose a peculiar effect of a cyclopropylidene system both on reaction rates and regioselectivity. In fact, the parent MCP as well as its derivatives exhibit a high reactivity in 1,3-dipolar cycloadditions with nitrones. In contrast, the related open chain isobutene and its derivatives are well known to enter 1,3-dipolar cycloadditions sluggishly [51c-d, 70]. For example, there is no chance to obtain a cycloadduct from 256 and an open chain trialkyl or tetraalkylethylene, as was obtained in the reaction of 256 with 270 and 271. 

Another synthetic approach for generating sugar-containing nitrones is by initial treatment of sugars with unsubstituted hydroxylamine. The resulting cyclic hydroxylamine of the tautomeric mixture (68a) and of the open chain oxime (68b) react with aldehydes to give the corresponding nitrones (69) (Scheme 2.24) (216-220). 

O - P h e n y 1 - /V - e r y t h r o s y 1 nitrone (336), as a Ci,C i-bis-electrophile, when subjected to the double addition of Grignard reagents (in a domino style), leads to acyclic hydroxylamine (338) via the formation of open-chain nitrone (337 ). The reaction proceeds at 0°C with variable diastereoselectivity ranging from medium to good, depending on the organometalic reagent used (Scheme 2.140) (564). 

Theoretical calculations at DFT level agree that the reactions of nitrones with silyl ketene acetal proceeds via 1,3-dipolar cycloaddition followed by the transfer of the silyl group, yielding an open-chain product (641). 

Hydroxydihydro-l,2-oxazines (20) are in equilibrium with the corresponding open-chain keto oximes (21) (70T1315), and a related tautomerism is exhibited by certain TV-oxides (22), the seco forms (23) of which are nitronic acids (78TL2339). 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

The H-NMR data indicated that C-aryl-/V-(2-carboxyalkyl)nitrones exist only as the open-chain isomers 41A in solution. However, in acylation reactions, they formed 0-acyl derivatives with the cyclic structure, whereas alkylation with phenacyl bromide led to the open-chain esters (84LA1545). 

There are two important routes to nitrones both start from hydroxyl amines. Open-chain nitrones are usually made simply by imine formation between a hydroxylamine and an aldehyde. 

Dihydroimidazole A-oxides have been extensively studied. l-Hydroxy-2,5-dihydroimidazole 3-oxides 499 are in tautomeric equilibrium with open-chain nitrones. Electron-withdrawing 2-substituents and a donor group in the 4-position favor the cyclic form. Oxidation gives stable radicals 500 that form cycloadducts with dipolarophiles (e.g., 501). Radicals formed from 2,5-dihydroimidazole 1-oxides or l-hydroxy-2,5-dihydroimidazoles can be formylated on nitrogen under Vilsmeier conditions and halogenated (NBS or NCS) on a 4-methyl group. 

The exolendo selectivity of the 1,3-dipolar addition of nitrones was regulated by the titanium salt as shown in Eq. (156) [398,399]. Aza-Cope rearrangement of a sugar-derived substrate initiated by the acetal cleavage with TiCl4 proceeded diastereoselec-tively to give the open-chain product (Eq. 157) [400]. 

Some radiolysis of the piperidine ring of 28, R = H was observed during the post-y-irradiation storage of PP under accelerated test condition [227], Formation of a nitrone 146 and open-chain nitroso- 144 and nitrocompounds 145 was reported (Subst. = an ester group as in 28). 

Cycloaddition between Open-Chain Nitrones and Olefins. 213... 

Since then researchers in the field of nitrone cycloaddition seem to have more or less tacitly assumed that secondary interactions play an important role in determining endo/exo selectivity also in the case of N-alkyl and N-arylnitrone cycloaddi-tions.2 However, our experimental endo/exo selectivity studies " for the reactions of cyclic and open-chain nitrones with Z-disubstituted dipolarophiles revealed a clear-cut dominance (77% in benzene) of the endo mode only in one case the reaction of 1-pyrroline-l-oxide with maleonitrile, a reaction where the steric effects... 

It is possible to compare the reactivity of some 1,3-dipoles inserted in cyclic structures with that of the same dipoles in open chains. This comparison, recalling that between cyclic and open-chain dienes (Section 4.1.3), is limited to two classes of 1,3-dipoles without a double bond , namely azomethine imines and oxides. For the former, there are data in Table 12 for the reaction with dimethyl acetylene dicarboxylate (iii) the cyclic azomethine imine (sydnone) is about 300 times less reactive than the open-chain cyanoazo-methine imine. In the case of nitrones, a typical comparison is. for reaction with ethyl crotonate in toluene at 100°C "... 

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

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