Labeling, deuterium rearrangement

In the course of two earlier syntheses of albene (794) (Vol. 4, p. 550), there was a question of the apparent emio-3,2-methyl shift in going from chiral 795 to 796, in which the chirality was greatly reduced. By examining the behavior of doubly labeled (deuterium and C) 795, Baldwin and Barden found that there was no e do-3,2-methyl shift the major pathway involved an eAro-methyl shift first, then a series of Wagner-Meerwein rearrangements (Scheme 63), with a minor route (shown in the scheme by dotted arrows) leading to the compound of opposite chirality. ... 

The first mass spectrometric investigation of the thiazole ring was done by Clarke et al. (271). Shortly after, Cooks et al., in a study devoted to bicydic aromatic systems, demonstrated the influence of the benzo ring in benzothiazole (272). Since this time, many studies have been devoted to the influence of various types of substitution upon fragmentation schemes and rearrangements, in the case of alkylthiazoles by Buttery (273) arylthiazoles by Aune et al. (276), Rix et al. (277), Khnulnitskii et al. (278) functional derivatives by Salmona el al. (279) and Entenmann (280) and thiazoles isotopically labeled with deuterium and C by Bojesen et al. (113). More recently, Witzhum et al. have detected the presence of simple derivatives of thiazole in food aromas by mass spectrometry (281). 

Nucleophilic substitution in cyclohexyl systems is quite slow and is often accompanied by extensive elimination. The stereochemistry of substitution has been determined with the use of a deuterium-labeled substrate (entry 6). In the example shown, the substitution process occurs with complete inversion of configuration. By NMR amdysis, it can be determined that there is about 15% of rearrangement by hydride shift accon any-ing solvolysis in acetic acid. This increases to 35% in formic acid and 75% in trifiuoroacetic acid. The extent of rearrangement increases with decreasing solvent... 

The rearrangement of the simplest possible case, 1,5-hexadiene, has been studied using deuterium labeling. The activation enthalpy is 33.5kcal/mol, and the entropy of activation is — 13.8eu. The substantially negative entropy reflects the formation of the cyclic transition state. 

Compound 1 undergoes rearrangement to 2 in SO2 at — 66°C. The deuterium label becomes imiformly scrambled among all the carbon atoms in 2. 

The di-7r-methane rearrangement has been studied in a sufficient number of cases to develop some of the patterns regarding substituent effects. When the central sf carbon is unsubstituted, the di-7i-methane mechanism becomes less favorable. The case of 1,1,5,5-tetraphenyl-l,4-pentadiene is illustrative. Although one of the products has the expected structure for a product of the di-7t-methane rearrangement, labeling with deuterium proves that an alternative mechanism operates ... 

They found that deuterium labeled 2-phenyl-5-methoxy-4-[(methoxy-d3)-carbonyl]oxazole (7) scrambled on heating to give a 1 1 equilibrium mixture of 7 and the corresponding rearranged ester 9 ... 

Deuterium-labeling and mass spectrometry prove that the mechanism of the thermal O to N rearrangement of 4-alkoxypyridines to N-alkyl-4-pyridones is intermolecular (88CS347). 

The rearrangement of the intermediate alkyl cation by hydrogen or methyl shift and the cyclization to a cyclopropane by a CH-insertion has been studied by deuterium labelling [298]. The electrolysis of cyclopropylacetic acid, allylacetic acid or cyclo-butanecarboxylic acid leads to mixtures of cyclopropylcarbinyl-, cyclobutyl- and butenylacetamides [299]. The results are interpreted in terms of a rapid isomerization of the carbocation as long as it is adsorbed at the electrode, whilst isomerization is inhibited by desorption, which is followed by fast solvolysis. 

Evidence for this mechanism is that optically active PhCHDCHs labeled in the ring with C and treated with GaBr3 in the presence of benzene gave ethylbenzene containing no deuterium and two deuteriums and that the rate of loss of radioactivity was about equal to the rate of loss of optical activity." The mechanism of intramolecular rearrangement is not very clear. The 1,2 shifts of this kind have been proposed " ... 

As a mechanistic hypothesis, the authors assumed a reduction of the Fe(+2) by magnesium and subsequent coordination of the substrates, followed by oxidative coupling to form alkyl allyl complex 112a. A ti—c rearrangement, followed by a syn p-hydride elimination and reductive elimination, yields the linear product 114 with the 1,2-disubstituted ( )-double bond (Scheme 29). This hypothesis has been supported by deuterium labeling experiments, whereas the influence of the ligand on the regioselectivity still remains unclear. 

More recently, a number of reports dealing with 1,3-sulfonyl shifts which proceed by other mechanisms have been published. For example, Baechler and coworkers suggested that the higher activation enthalpy observed for the isomerization of the deuterium labeled methallyl sulfone 72 in nitrobenzene at 150°C as compared to the corresponding sulfide, together with the positive entropy of activation may be taken as evidence for a homolytic dissociation mechanism (equation 44). A similar mechanism has also been suggested by Little and coworkers for the gas-phase thermal rearrangement of deuterium labelled allyl sec-butyl sulfone, which precedes its pyrolysis to alkene and sulfur dioxide. 

Kametani et al. (163-165) studied the Stevens rearrangement using sodium bis(2-methoxyethoxy)aluminum hydride as the base in dioxane. It became clear from studies using deuterium-labeled or optically active compounds that quasi-axially oriented hydrogens at C-8 and C-14 were independently abstracted by the base, leading to a spirobenzylisoquinoline and an 8-... 

Tenney, Boykin and Lutz<58) labeled carbon 1 with either 14C or deuterium and showed that a hydrogen or phenyl migration was not involved in the rearrangement ... 

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