Isotopic labelling rearrangement

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). 

The occurrence and extent of rearrangement of the 2-butyl cation have also been investigated by solvolysis studies using isotopic labeling. When 2-butyl tosylate is solvolyzed in acetic acid, C-2/C-3 rearrangement occurs only to the extent of 9% in the 2-butyl acetate which is isolated.Thus, under these conditions, most of the reaction proceeds by direct participation of the solvent. 

Parallel and reversible reactions. The isomerization of allyl phenyl sulfide is a degenerate rearrangement made detectable by isotopic labeling of one end of the allyl group, permitting kinetic monitoring by NMR techniques.12... 

A 1,2-shift has been observed in radicals bearing an OCOR group at the p-carbon where the oxygen group migrates as shown in the interconversion of 36 and 37. This has been proven by isotopic labeling experiments and other mechanistic explorations. A similar rearrangement was observed with phosphatoxy alkyl radicals such as 38. ... 

The latter method is improved by use of the 2,2-dimethyl derivative.273 The rearrangement is faster and the stability of the orthoester to hydrolysis is better. Isotopic labeling showed that the rearrangement occurs by ionization at the tertiary position. 

Retention of configuration is expected for conversion of 3 to 59a. It is curious, however, for the rearrangement of 59a to 60a, since the most obvious pathway—opening of the O—O bond followed by rotation and reclosing—should lead to inversion of configuration. Double isotopic labeling with, 80 was used to show that the rearrangement of 59a to 61a, as well as the initial oxidation of 3 to 59a, is fully intramolecular. 

Even more complex experiments have been performed on matrix isolated Fe(C0)4, generated by UV photolysis of Fe(C0)5. Isotopic labelling coupled with CW-CO laser pumping (65) of the CO stretching vibrations ( 1900 cnrl) showed that the rearrangement mode of Fe(C0)4 follows an inverse Berry pseudo-rotation as shown in Figure 8. 

The rearrangement of platinacyclobutanes to alkene complexes or ylide complexes is shown to involve an initial 1,3-hydride shift (a-elimina-tion), which may be preceded by skeletal isomerization. This isomerization can be used as a model for the bond shift mechanism of isomerization of alkanes by platinum metal, while the a-elimination also suggests a possible new mechanism for alkene polymerisation. New platinacyclobutanes with -CH2 0SC>2Me substituents undergo solvolysis with ring expansion to platinacyclopentane derivatives, the first examples of metallacyclobutane to metallacyclopentane ring expansion. The mechanism, which may also involve preliminary skeletal isomerization, has been elucidated by use of isotopic labelling and kinetic studies. 

The formation of o-terphenyl is of special interest, and by isotopic labeling it was shown that this compound is formed by consecutive phenyl and hydrogen migrations. The key intermediate in this sequence of rearrangements is the formation of a highly strained isobenzene (Scheme 20). Several alternative mechanisms are not compatible with the observed distribution of isotopes and could thus be ruled out.106... 

Tebbe and co-workers reported the first olefin metatheses between titanocene-methyli-dene and simple terminal olefins [13]. They showed cross-metathesis between isotopically labeled isobutene and methylenecyclohexane to be catalyzed by titanocene-methylidene. This process is referred to as degenerate olefm metathesis as it does not yield any new olefin (Scheme 14.6). The intermediate titanacyclobutane has been isolated and characterized [14], and its stability [15] and mechanism of rearrangement [16] have been investigated. 

The rearrangements of b-(acyloxy), (i-(phosphatoxy)alkyl, and related systems have been reviewed [51,52] and representative kinetic data are given in Table 2 above. As revealed by isotopic labeling experiments, the acyloxy... 

There exist early examples of this transformation [507, 508], but due to the symmetric structure of the alkene part, only isotope labeling, etc., allowed the exclusion of a prototropic rearrangement. Furthermore, due to the high reaction temperatures of 340 °C and above, several different products are formed. A low-temperature version (77 K) of this reaction via the radical cation has been reported [509]. The chirality transfer has been studied and a detailed mechanistic investigation has been conducted [510] typical experiments in that context were the reactions of substrates such as 155 and 157 (Scheme 1.70). 

Example Isotopic labeling does not only reveal the original position of a rearranging atom, but can also reveal the rate-determining step of multi-step reactions by its marked influence on reaction rates. Thus, the examination of H/D and isotope effects led to the conclusion that the McLafferty rearrangement of aliphatic ketones (Chap. 6.7) rather proceeds stepwise than concerted. [68]... 

In times past it was thought that indoles already bearing an alkyl substituent at C-3 were further alkylated by direct attack at C-2. However, although 2,3-dialkylindoles are readily formed the reaction still involves attack at C-3. This can be demonstrated by the example in Scheme 7.3, where 3-(4 -hydroxybutyl)indole, containing an isotopic label located at C-T, is treated with boron trifluoride in diethyl ether. Two 1,2,3,4-tetrahy-drocarbazoles (l,2,3,4-tetrahydrodibenzo[6,J)pyrroles) are formed in a ratio of 1 1. These differ only in the position of the label. This result indicates that a 3,3-spiroindoleninium intermediate is formed first, and this then undergoes rearrangement of either bond a or bond b to C-2. As the two bonds a and b are identical, equal amounts of the tetrahydrocarbazoles... 

Scheme 16.5. The FVP of isotopically labeled phthalic anhydride (7) indicates a scrambling of carbon atoms. Yet, it is not clear whether a reversible ring contraction of 4 is responsible for this exchange or if it takes place already at the stage of ketenecarbene (12). According to recent calculations, the barrier for the rearrangement 4 9 is only 32 kcal/...

Mechanistically this process is interesting since it involves a carbene-carbene rearrangement as was shown by Skattebol [110], Baird [111] and Brinker [112] using isotopically labeled substrates. 

Van den Berg et al. suggested an intramolecular Stevens rearrangement of the oxo-nium ylide to ethyl methyl ether to interpret carbon-carbon bond formation463 [Eq. (3.55)]. Olah and coworkers, however, provided evidence (based on isotopic labeling studies) that the oxonium ylide undergoes intermolecular methylation to ethyl dimethyloxonium ion [Eq. (3.56)] instead of Stevens rearrangement 447... 

---