Hydride shift process

Reaction of cyclooctene with trifiuoroacetic acid occurs by a hydride shift process. 

The chemoselectivity of the reaction favors insertion in the most electron-rich C—H bond available to produce an oxazolidinone (Eqs. (5.6) and (5.7)) [33, 49, 50). When a bicyclic system is formed, the C—H amination reaction leans toward the formation of the cis-isomer. The scope of the reaction is large and many examples of carbamates derived from primary and tertiary alcohols are known. The use of carbamates derived from secondary alcohols is, however, more limited to substrates having conformational bias and/or very reactive C—H bonds (benzylic and allyl-ic) [51, 52]. Otherwise the formation of the corresponding ketone is observed, probably via a hydride shift process, similar to what is observed in C—H bond insertion with metal carbene [53, 54). 

The in situ-generated iminium could also be exploited as hydride acceptor, via which inert C(sp )-H bond could be functionalized to C-N bond efficiently. Seidel et al. reported a trifluoroacetic acid-catalyzed cascade [1,6]-hydride transfer/cy-clization of 77 to synthesize 7,8,9-trisubstituted dihydropurine derivatives 78 (Scheme 27) [73]. TFA plays two roles in this process (1) promotion of imine formation and (2) protonation of imine for acceleration of the hydride shift process. Meth-Cohn and Volochnyuk et al. reported similar reactions in 1967 [71] and 2007, respectively [72]. 

An oxidation-reduction sequence was used to invert stereochemistry at C-3 in a preparation of some 2 -deoxy-p-D-threo-pentofuranosyl pyrrolo-P3nimidines (42, R=OH). i A hydride shift process (Scheme 5) was used to make 3 -deoxy-p-D-threo-pentofuranosyl nucleosides of type (43), 2 whilst a similar process is Involved in the formation of (43, B=Ad) by treatment of 2, 3 -di-0-tosyladenoslne with liEtaBH the same product (43, B=Ad) was also obtained, in higher yields, by the same reduction of the analogous D-arabino-and D-lyxo-systems. ... 

As previously considered in this chapter, propagation proceeds via oxonium and/or carboxonium ions, and these species are reasonably assumed to remain stable and active. The formation of formaldehyde during the process, resulting from thermodynamic depolymerization of triox-ane and to a lesser extent from unzipping of open-chain active ends, indicates that carboxonium ions are in equilibrium with oxonium ions. This is also supported by the observation of methoxy and formate end groups resulting from hydride shift processes in transfer reactions to... 

Extensive studies on the Wacker process have been carried out in industrial laboratories. Also, many papers on mechanistic and kinetic studies have been published[17-22]. Several interesting observations have been made in the oxidation of ethylene. Most important, it has been established that no incorporation of deuterium takes place by the reaction carried out in D2O, indicating that the hydride shift takes place and vinyl alcohol is not an intermediate[l,17]. The reaction is explained by oxypailadation of ethylene, / -elimination to give the vinyl alcohol 6, which complexes to H-PdCl, reinsertion of the coordinated vinyl alcohol with opposite regiochemistry to give 7, and aldehyde formation by the elimination of Pd—H. 

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... 

This result can be explained by a transarmular 1,5-hydride shift. Many similar processes have been documented. ... 

Because of Us high polarity and low nucleophilicity, a trifluoroacetic acid medium is usually used for the investigation of such carbocationic processes as solvolysis, protonation of alkenes, skeletal rearrangements, and hydride shifts [22-24] It also has been used for several synthetically useful reachons, such as electrophilic aromatic substitution [25], reductions [26, 27], and oxidations [28] Trifluoroacetic acid is a good medium for the nitration of aromatic compounds Nitration of benzene or toluene with sodium nitrate in trifluoroacetic acid is almost quantitative after 4 h at room temperature [25] Under these conditions, toluene gives the usual mixture of mononitrotoluenes in an o m p ratio of 61 6 2 6 35 8 A trifluoroacetic acid medium can be used for the reduction of acids, ketones, and alcohols with sodium borohydnde [26] or triethylsilane [27] Diary Iketones are smoothly reduced by sodium borohydnde in trifluoroacetic acid to diarylmethanes (equation 13)... 

Examine the transition state for the hydride shift. Calculate the barrier from the more stable initial carbocation. Is the process more facile than typical thermal rearrangements of neutral molecules (.05 to. 08 au or approximately 30-50 kcal/mol) Is the barrier so small (<.02 au or approximately 12 kcal/mol) that it would be impossible to stop the rearrangement even at very low temperature Where is the positive charge in the transition state Examine atomic charges and the electrostatic potential map to tell. Is the name hydride shift appropriate If not, propose a more appropriate name. 

These transfer processes seem to be /3-hydride shift reactions, typical of... 

The other commonly quoted industrial photochemical process is the production of vitamin D3 involving a photochemical electrocyclic ring opening followed by a thermal 1,7-hydride shift (Scheme 7.2). This is a further example of a successful low quantum yield process in this case there is no viable thermal alternative. Vitamin A acetate has also been produced commercially using a photochemical isomerization process to convert a mixed tetra-alkene precursor to the all-trans form. 

Hydride and 1,2-alkyl shifts represent the most common rearrangement reactions of carbenes and carbenoids. They may be of minor importance compared to inter-molecular or other intramolecular processes, but may also become the preferred reaction modes. Some recent examples for the latter situation are collected in Table 23 (Entries 1-10, 15 1,2-hydride shifts Entries 11-15 1,2-alkyl shifts). Particularly noteworthy is the synthesis of thiepins and oxepins (Entry 11) utilizing such rearrangements, as well as the transformations a-diazo-p-hydroxyester - P-ketoester (Entries 6, 7) and a-diazo-p-hydroxyketone -> P-diketone (Entry 8) which all occur under very mild conditions and generally in high yield. 

The observed methane generation points to a plausible I —> III or II - III transformation, but it does not distinguish which of the structures (II or III) is the metathesis-active carbene. This matter is mechanistically significant with regard to the chain termination process. Type III may terminate by a bimolecular dimerization sequence as in Eq. (11), or it may convert to a 7r-olefin complex via an uncommon 1,2-hydride shift ... 

Two significant items were confirmed in this work (a) Molybdenum, and most probably tungsten, can expand its sphere of coordination beyond 6 and (b) hydride shifts transforming olefins to allyls or 7r-allyls, via v -> (t and 77 - Tj3 processes, respectively, are feasible in metals that are known to produce active metathesis catalysts. 

Of particular importance are recent results on the energetics of the exo-2,3-hydride shift in the 2,3-dimethyl-2-norbornyl and the l,2,3,4-tetramethyl-2-norbornyl cations. Line broadening studies reveal a free energy of activation of 6-6 and 7-3 kcal mole for this process in the respective ions (Huang eta/., 1973 Jones et a/., 1974). 

Another result of the kinetic analysis of the 3,2- and 1,2,6-hydride shifts which tends to support the claissical view of the ion is the close similarity in the /I-factors in the Arrhenius equation. is 10 for the 3,2-shift and 10 for the 1,2,6-equilibration process. Both factors are roughly normal and might be expected for rearrangements where the rate-determining step is a relatively slow hydride transfer between carbon atoms in the classical ion. 

On the other hand, if the non-classical ion is a stable intermediate, the transition state for the 3,2 hydride shift requires a subst mtial reorganization, including the cleavage of the cyclopropyl ring, and, by analogy with unimolecular gas phase processes, a much higher pre-exponential factor might be expected. [In the cyclopropane-propylene reaction log A is 1ST 7 (Chambers and Kistiakowsky, 1954).] Contrary to expectation, the observed pre-exponential for the 3,2-shift is actually a little lower than for the 1,2,6-equilibration process. 

In contrast to the isomerization of 39, the retention of optical activity for the conversion of 41 to 42 is very small. However, the loss of activity cannot be explained by a degenerate vinylcyclopropane rearrangement, since the recovered starting material ([(X]54g = +32 ) shows essentially complete retention of chirality. An alternative explanation involves competing stereoselective processes in a chiral intermediate (41a ). For 41a a hydride shift from the allylic position, C2, might compete with the migration from C6 to Cl. This possibility can be probed by... 

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