Deuterium labelling isomerization

With 6-alkenoic acids the intermediate radical partially cyclizes to a cyclopentyl-methyl radical in a 5-exo-trig cycHzation [139] (Eq. 6) [138 a, 140] (see also chap. 6). To prevent double bond migration with enoic acids the electrolyte has to be hindered to become alkaline by using a mercury cathode. Z-4-Enoic acids partially isomerize to -configurated products. Results from methyl and deuterium labelled carboxylic acids support an isomerization by way of a reversible ring closure to cyclopropyl-carbinyl radicals. The double bonds of Z-N-enoic acids with N > 5 fully retain their configuration [140]. 

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. 

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. 

Further support for the proposed mechanism of hydride-catalyzed dihaptoacyl isomerization is derived from deuterium labelling studies. When the reaction is conducted with an excess of Th[(( 3)505]2 2)2 the enolate product is selectively deuterated at the H position (Figure 3b) as expected from eq.(12). Furthermore, nmr studies confirm the production of... 

Intriguingly, the conical intersection model also suggests that E,Z-isomerization of acyclic dienes might be accompanied by conformational interconversion about the central bond, reminiscent of the so-called Hula-Twist mechanism for the efficient ,Z-photo-isomerization of the visual pigment rhodopsin in its rigid, natural protein environment101. A study of the photochemistry of deuterium-labelled 2,3-dimethyl-l,3-butadiene (23-d2) in low temperature matrices (vide infra) found no evidence for such a mechanism in aliphatic diene E,Z -photoisomerizations102. On the other hand, Fuss and coworkers have recently reported results consistent with the operation of this mechanism in the E,Z-photoisomerization of previtamin D3 (vide infra)103. 

One such typical transformation is the thermal isomerization of the spiropentane derivative 76 into triene 80 which is assumed to occur via the diene intermediate 78 with the intermediate participation of the cyclopropyl-trimethylenemethane (TMM) 77 and the vinyl-TMM 79 diradicals (equation 29)44. It was shown by using deuterium labels that the diradical 79 forms the triene 80 by 1,6-hydrogen shift. The pathway 76 — 80 which occurs via tetramethylene-ethane diradical was recognized as a less probable route. 

Such stability is only relative, however, given the possibility of the acid-catalyzed 1,2-shift of a proton observed in some olefin epoxides of general structure 10.10 (Fig. 10.3) [12], Such a reaction occurs in the in vivo metabolism of styrene to phenylacetic acid the first metabolite formed is styrene oxide (10.10, R = Ph, Fig. 10.3, also 10.6), whose isomerization to phenyl-acetaldehyde (10.11, R = Ph, Fig. 10.3) and further dehydrogenation to phenylacetic acid has been demonstrated by deuterium-labeling studies. A com-... 

To elucidate the reaction pathway, deuterium-labeled allenyl pinacol boronate 10 was prepared, and the addition reaction with hydrazonoester 6 was conducted in the presence of Bi(OH)3 and Cu(OH)2 (Scheme 4). In both Bi- and Cu-catalyzed cases, the reactions proceeded smoothly (in quantitative yields in both cases). In the Bi(OH)3-catalyzed reaction, a major product was allenyl compound 11, in which the internal position was deuterized. It was assumed that a propargyl bismuth was formed via transmetalation from boron to bismuth, followed by addition to hydrazonoester via y-addition to afford allenyl compound 11. Thus, two y-additions could selectively provide a-addition products [75, 76, 105, 106]. It was confirmed that isomerization of 10 did not occur. Recently, we reported Ag20-catalyzed anti-selective a-addition of a-substituted allyltributyltin with aldehydes in aqueous media [107], On the other hand, in the Cu(OH)2-catalyzed reaction, a major product was propargyl compound 12, in which the terminal position was deuterized. A possible mechanism is that Cu(OH)2 worked as a Lewis acid catalyst to activate hydrazonoester 6 and that allenyl boronate 10 [83-85] reacted with activated 6 via y-addition to afford 12. 

In the hydroformylation of optically active alkenes, all aldehydes were shown to be formed with predominant retention of configuration.53,54 This was interpreted to prove, in accordance with the transformation of deuterium labeled alkenes,55 56 that stereoselective hydrogen shifts of the coordinated olefins occur without dissociation of the isomeric alkenes.30... 

For example, the ene reaction proceeds stereoselectively in a suprafacial manner specifically, oxygen attack and hydrogen removal take place on the same side of the double bond. As a result, neither racemization of optically active com-pounds nor cis-trans isomerization occurs. Diradical or dipolar intermediates are not consistent with these observations. The lack of a Markovnikov-type directing effect also rules out dipolar intermediates.360 399 Isotope effects observed in the reaction of different deuterium-labeled 2,3-dimethyl-2-butenes indicated that... 

Early kinetic studies on the structural isomerization of cyclopropane to propene provided estimates of activation parameters73 75 and prompted speculation that the reaction might well involve a trimethylene diradical intermediate. This possibility seemed reinforced when the thermal interconversion of the els and trans isomers of l,2-d2-cyclo-propane at 414 to 474 °C (equation 1) was reported in 195876. This structurally degenerate isomerization was found to be substantially faster than conversion to deuterium-labeled propenes—about 24 times faster at the high pressure limit76 77. 

The thermal stereomutations of deuterium-labeled phenylcyclopropanes (Scheme 3) were studied in a progressive manner. First, the racemic and both achiral isomers were synthesized to provide material for kinetic work and to verify analytical methods 62. The isomerizations among these three isomers at 309.3 °C were followed using either 2H decoupled H NMR spectroscopy or Raman spectroscopy the two kinetic parameters (k, + k22) = 0.36 x 10 5 s 1 and (k2 + k]2) - 1.07 x 10"5 s 1 at 309.3 °C were measured. Published spectra of both sorts for authentic samples of syn, anti and trans isomers, and of thermal reaction mixtures, provided... 

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