TPAP, oxidation of alcohols

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. 

R. Ciriminna and M. Pagliaro, Tailoring the Catalytic Performance of Sol-Gel-Encapsulated Tetra-n-propylammonium Perruthenate (TPAP) in Aerobic Oxidation of Alcohols, Chem. Eur. J., 2003, 9, 5067. 

R. Ciriminna, S. Campestrini, M. Carraro and M. Pagliaro, Sol-gel entrapped TPAP an off-the-shelf catalyst series for the clean oxidation of alcohols, Curr. Org. Chem., 2008, 12, 257. 

The oxidation of alcohols to carbonyl compounds has been studied by several authors and a variety of methods have been used. Papers concerned vith such oxidations are illustrated (Scheme 3.26). Good results have been obtained using pyridinium chlor-ochromate (PCC) adsorbed onto silica gel for the selective oxidation of unsaturated substrates e.g. terpene [135] and furanyl derivatives [136]. Steroidal homoallylic alcohols can be converted to the corresponding 4-ene-3,6-diones using tetrapropylammo-nium per-ruthenate (TPAP) in catalytic amounts [137]. In this case, the oxidising agent is N-methyl morpholine N-oxide (NMO). 

R. Lenz, S. V. Ley, Tetra-n-propyl ammonium perruthenate ( TPAP)-Catalyzed Oxidations of Alcohols using Molecular Oxygen as a Co-oxidant, J. Chem. Soc., Perkin Trans. 1, (1997) 3291-3292. 

Jones reagent is used to oxidize the aldehyde here to an acid. In general only the first two reagents listed in the Tips oxidi/e aldehydes to acids. TPAP can be used for oxidation of alcohols to aldehydes, ketones, or acids. The others are used for oxidizing alcohols to aldehydes or ketones.27... 

A milestone in the routine employment of perruthenate in the oxidation of alcohols was established with the publication by Griffith, Ley et al. in 1987 on the catalytic use of tetra- -propylammonium perruthenate (TPAP).11 The presence of the tetra- -propylammonium cation renders this compound soluble in apolar media and allows the existence of a high concentration of perruthenate ion in organic solvents. The tetra- -propylammonium perruthenate is easily prepared and can be employed catalytically in CH2CI2 solution in the oxidation of alcohols to ketones and aldehydes, using /V-methyl morpholine A-oxide (NMO) as the secondary oxidant. 

Because of the high price of TPAP, research is being made in order to develop new protocols and modified reagents that allow the recovery of perruthenate—present as TPAP or in other compounds—after oxidation of alcohols. Proposed alternatives include employing TPAP in the presence of ionic salts,62 on an Amberlist anion exchange resin63 or on a silicate.69b,c,d... 

General Procedure for Oxidation of Alcohols with TPAP... 

Alcohols can be oxidized with TPAP in the presence of tertiary amines.88 Secondary amines are transformed into imines under the action of TPAP.89 At the time of writing, the scientific literature contains no data regarding the possibility of performing selective oxidation of alcohols in the presence of secondary or primary amines, with the exception of the following example in which a secondary amine is trapped by reaction with an aldehyde, resulting from the selective oxidation of a primary alcohol.90... 

It is possible to oxidize alcohols with TPAP in the presence of free phenols.95 Although, there is one instance in which it has been published that, unless a phenol is acetylated, an oxidation with TPAP fails.73 Oxidation-prone heterocycles, such as pyrroles96 and indoles,97 are not affected by TPAP during the oxidation of alcohols. 

Organometallic compounds possessing carbon-tin bonds can resist he action of TPAP during the oxidation of alcohols.99... 

In rare cases, ketones obtained by the oxidation of alcohols with TPAP suffer an in situ over-oxidation, resulting in the introduction of an alkene conjugated with the ketone.106 For example, this happens when thermodynamics are greatly favored by aromatization. 

TPAP is able to produce the isomerization of allylic alcohols into saturated ketones and aldehydes.107 This reaction is not performed under the standard conditions for the oxidation of alcohols, employing NMO as secondary oxidant, and is only efficient under very exacting experimental conditions. 

The oxidation to the enone was realized with catalytic amounts of tetra-n-propylammonium perruthenate (TPAP)21 (46), which is a mild oxidant for conversion of multifunctionalized alcohols to aldehydes or ketones. Catalytic TPAP oxidations are carried out in the presence of stoichiometric or excess A-methylmorpholine-A-oxide (NMO)22 (47) as cooxidant. Other common reagents for oxidation of alcohols are e.g. DMS0/C202C1223, Dess-Martin periodinane24, PCC25, PDC26 or the Jones reagent27. 

Fig. 14.14. TPAP oxidation of an alcohol to an aldehyde TPAP stands for tetrapropylammonium perruthenate.

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). 

F.i. Tetrapropylammonium Perruthenate-Ley Oxidation. Ruthenium derivatives have been used for oxidation reactions. A particularly useful one is TPAP, introduced by Ley for the oxidation of alcohols and called Ley oxidation. 1 2 a very mild oxidizing agent that is compatible with many sensitive... 

The oxidation of alcohols with (l,l-dimethylethyl)benzene-sulfenamide is extremely mild and many sensitive functional groups such as epoxides and alkenes are tolerated hy the reaction conditions (eq 5). In the case of alcohol 1, oxidation with tetrapropylammonium perruthenate (TPAP) resulted in only 58% yield and Swern oxidation was unsuccessful. Epimerizable aldehydes such as the protected phenylglycinol 2 do not undergo racemization when oxidized (eq 6). ... 

Toward this end, aldehyde 2.188 was protected as the acetal, which was followed by oxidative removal of PMB group and subsequent TPAP oxidation of resulting alcohol to deliver the aldehyde 2.212. Gratifyingly, the subjection of 2.212 to the (-)-MlB-catalyzed asymmetric vinylation reaction (4-methyl-1-pentyne, Cy2BH, Et2Zn, (-)-MlB, toluene, -5 °C, 1.5 h) afforded the desired (17/f)-alcohol 2.213 with excellent stereoselectivity (dr = 32 1) as determined by HPLC. 

Osborn and coworkers [108-110] reported that CuCl in combination with OSO4 or Pr4NRu04 (TPAP) catalyzes the aerobic oxidation of alcohols. The scope is rather limited, however, and the system would not appear to have any advantages over the earlier described ruthenium- and palladium-based systems. Similarly an Mo02(a-cac)2-Cu(N03)2 system[lll] resulted in rather low activities and selectivities for the oxidation of primary activated and secondary alcohols. 

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