Complex hydrides deuterium oxide

During the course of these mechanistic studies a wide range of possible applications of this reaction have been revealed. When the reduction is carried out with lithium aluminum deuteride and the anion complex decomposed with water, a monodeuterio compound (95) is obtained in which 70% of the deuterium is in the 3a-position. Reduction with lithium aluminum hydride followed by hydrolysis with deuterium oxide yields mainly (70 %) the 3j5-di-epimer (96), while for the preparation of dideuterio compounds (94) both steps have to be carried out with deuterated reagents. ... 

If the mechanism is dissociative (Fig. 2), then oxidative addition occurs (step 3) to give a platinum(IV) hydride. This can then lose HC1 (step 4) and gain DC1 (step 5), to and from the solvent. The plati-num(IV) deuteride can then revert to a 7r-complex with deuterium in the aromatic ring (step 6), and this deuterated benzene is lost (step 7) with regeneration of the catalyst. 

A mechanism which is consistent with the various experimental results for olefin formation involves the initial abstraction of the hydrazone proton (103 - 106)82 In this case, however, expulsion of the tosylate anion is associated with the abstraction of a second hydrogen from C-16 instead of hydride attack on the C=N bond (compare 97 - 98 and 106 - 107). Expulsion of nitrogen from the resulting intermediate (107) yields an anion (108) which is most probably stabilized in the form of a metal complex and can be readily decomposed by water to give an olefin (109). This implies that 17-d1-androst-16-ene (104) can be prepared by using deuterium oxide as the sole deuterated reagent.82... 

The Wacker reaction has found most use for the oxidation of terminal alkenes to give methyl ketones. It is believed to take place by an initial trans hydroxypallada-tion of the alkene to form an unstable complex that undergoes rapid p-elimination to the enol 112 (5.112). Hydropalladation then reductive elimination completes the overall process that involves transfer of hydride ion from one carbon to the other, via the palladium atom. The hydride migration is required to explain the observation that when the reaction is conducted in deuterium oxide, no deuterium is incorporated in the aldehyde produced. 

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. 

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. 

Another instructive scenario may be found when considering the metalation of arenes. There are two distinct mechanisms for the metalation of aromatic C-H bonds - electrophilic substitution and concerted oxidative addition (Box2). The classical arene mercuration, known for more than a century, serves to illustrate the electrophilic pathway whereas the metal hydride-catalyzed deuterium labeling of arenes document the concerted oxidative addition mechanism [8, 17]. These two processes differ both in kinetic behavior and regioselectivity and thus we may appreciate the need to differentiate these two types of process. However, the choice of C-H bond activation to designate only one, the oxidative addition pathway, creates a similar linguistic paradox. Indeed, it is hard to argue that the C-H bond in the cationic cr-complex is not activated. 

Isotope effects can be used to choose the most likely path. When ethylene is oxidized in deuterated water, the acetaldehyde contains no deuterium hence, all four hydrogens in the acetaldehyde must come from the ethylene. Thus, if the slow step of the reaction involves the formation of acetaldehyde, the activated complex for this slow step would involve a hydride transfer, and a primary isotope effect would be expected when deuterated ethylene is used. Actually, the isotope effect kn/ko was found to be only 1.07. In Paths 1 and 3, the slow step is, respectively, the decomposition of a 7r-complex and a a-complex to product, and they would be expected to display a primary isotope effect. However, in Path 2, the rate-determining step is the rearrangement of a 7r-complex to a (T-complex. Since no carbon-hydrogen bonds are broken, no primary isotope effect would be expected. Thus, Path 2 is consistent with all the experimental facts. Paths involving oxypalladation adducts, first suggested by the Russian workers (32), are now generally accepted (19, 28, 32). 

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