TPAP oxidation mechanism

Fig. 17.15. Mechanism of the TPAP oxidation of an atcohot to an aldehyde (TPAP stands for tetrapropylammonium per-ruthenate). The effective oxidant is a Ru(VII) oxide, other than in Figure 17.12 where a Ru(VIII) oxide is employed. Here, the stoichiometrically used oxidizing agent is N-methylmorpholin-/V-oxide ("NMO"), whereas in Figure 17.12 NaI04 is used.

The effective oxidant in the TPAP oxidation of alcohols is the perruthenate ion, a Ru(VII) compound. This compound is employed only in catalytic amounts hut is continuously replenished (see below). The mechanism of the alcohol — aldehyde oxidation with TPAP presum-... 

The effective oxidant in the TPAP oxidation of alcohols is the perrathenate ion, a Ru(VII) compound. This compound is employed in catalytic amounts only but is continuously replenished (see below). The mechanism of the alcohol —> aldehyde oxidation with TPAP presumably corresponds to the nonradical pathway of the same oxidation with Cr(VI) (Figure 14.10, top). Accordingly, the key step of the TPAP oxidation is a /3-elimination of the ruthenium(VII) acid ester B. The metal is reduced in the process to ruthenium(V) acid. 

It is open to speculation whether the same mechanism would apply to the more common oxidations with TPAP, in which the perruthenate ion operates in an apolar environment. 

Modern variations include the in situ, and thus catalytic, use of this high-valent selective reagent, not only for alcohols but also for ethers (see later). Ru(VII) (perruthenate) in the compounds tetra-n-butylammonium perruthenate (TBAP) and tetra-n-propylammonium perruthenate (TPAP) has found wide application in alcohol oxidation. Ru-oxo complexes with valence states of IV to VI are key intermediates in, for example, the selective oxygen transfer to alkenes, leading to epoxides. On the other hand 16-electron Ru(II) complexes can be used to catalyse hydrogen transfer thus these are excellent catalysts for oxidative dehydrogenation of alcohols. A separate section is included to describe the different mechanisms in more detail. 

Sparse attention has been paid to the mechanism of perruthenate-catalysed alcohol oxidations [103]. Although TPAP can act as a three-electron oxidant... 

Mechanism The mechanism of the oxidation of alcohols with TPAP corresponds to the non-radical Cr(VI) oxidation. The perruthenate ion reacts with alcohols to form the ester of ruthenium(VII) acid A, which on elimination gives an aldehyde and reduced ruthe-nium(V) acid B (Scheme 7.10). It is believed that NMO reoxidizes the ruthenium(V) acid to perruthenate faster than the ruthenium(V) acid could attack on alcohol molecule. 

Practical Cr -catalyzed oxidations of alcohols have not been adopted widely, but Pr4N+ Ru04 (TPAP, tetrapropylammonium perruthenate) catalyzes the oxidation of alcohols to aldehydes by a stoichiometric oxidant such as NMO, H2O2, or O2 itself. The Ru(VII) complex oxidizes alcohols by the same mechanism described earlier for stoichiometric Cr species. The stoichiometric oxidant then reoxidizes the Ru(V) by-product back to Ru(VII). 

A series of homo-allylic steroidic alcohols were oxidized with N-methyl morpholine N-oxide (NMO) in the presence of tetrapropylammonium perrhutenate (TPAP) (Eq. 70, see Ch. 9, p. 358).The mechanism probably implies the preliminary oxidation of the alcohol. A labile silyl enol ether is preserved under the conditions specified. 

In 2012, Rueping et al. reported the proline-mediated reaction of 1,3-diketones with aldehydes to provide 2-hydroxy-3,4-dihydro-2//-pyran derivatives in good to excellent yields [46]. The reaction mechanism involves a Knoevenagel-Michael addition sequence with subsequent hemiacetalization. The haniacetal was oxidized with TPAP/ NMO or PCC to give the corresponding lactones 96. An enantioselective variant utilizing stoichiometric amounts of an... 

Sparse attention has been paid to the mechanism of perruthenate-catalyzed alcohol oxidations [55]. Although TPAP can act as a three-electron oxidant (Ru " Ru ) the fact that it selectively oxidizes cyclobutanol to cyclobutanone and tert-butyl phenyl-methanol to the corresponding ketone, militates against free radical intermediates and is consistent with a heterolytic, two-electron oxidation [55, 56]. Presumably, the key step involved P-hydride elimination from a high-valent, e. g., alkoxyruthenium (VII) intermediate followed by reoxidation of the lower valent rathenium by dioxygen. However, as shown in Scheme 4.12, if this involved the Ru "/Ru couple the reoxidation would require the close proximity of two ruthenium centers, which would seem unlikely in a polymer-supported catalyst A plausible alternative, which can occur at an isolated mthenium center involves the oxidation of a second molecule of alcohol, resulting in the reduction of mthenium(V) to rathenium(III), followed by reoxidation of the latter to ruthenium (VII) by dioxygen (see Scheme 4.12). 

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