Oxidation using TPAP

There are few reported oxidations of this type with TPAP in organic solvents, one of the advantages of the reagent being that the alcohol-to-aldehyde oxidation rarely proceeds further. One natural product which did involve such a step is antascomicin B using TPAP/NMO/PMS/CH Cl [85], In aqueous base however [RuO ] is a much more powerful oxidant than TPAP in organic media, perhaps because oxidation of aldehydes to carboxylic acids may proceed via an aldehyde hydrate, the formation of which is inhibited by the molecular sieves used in catalytic TPAP systems. 

Typical examples are listed in Table 2.1. A few oxidations are effected by RuO but in general it is too powerful an oxidant for this purpose. The system RuCyaq. NaCl-CCy Pt anode oxidised benzyl alcohol to benzaldehyde and benzoic acid and p-anisaldehyde to p-anisic acid [24], and a wide range of primary alcohols and aldehydes were converted to carboxylic acids, secondary alcohols to ketones, l, -diols to lactones and keto acids from RuOj/aq. NaCl pH 4/Na(H3PO )/Pt electrodes (Tables 2.1-2.4). The system [RuO ] "/aq. K3(S303)/Adogen /CH3Cl3 oxidised benzyhc alcohols to aldehydes [30]. The oxidation catalyst TPAP (( Pr N)[RuO ]) (cf. 1.3.4) is extremely useful as an oxidant of primary alcohols to aldehydes and secondary alcohols to ketones without... 

Some oxidations used the system TPAP/NMO/PMS/CH3CN (cf 2.4.2.2, Fig. 2.17) [155], cf mech. Ch. 1 [156], or TPAP/NMO/CH3CI3-CH3CN/PMS [66]. In one instance TBAP/NMO/PMS/CH Cl (rather than TPAP) was used for an oxidation in which a triple bond was affected by an oxidation involving 2-propar-gyloxy-cyclopentanone with a -CH CCH substituent [157]. 

The Grignard reagent tirsl adds nucleophilically to the carbonyl carbon atom and forms a secondary alcohol (see also Chapters 1 and 2). This is subsequently oxidized to ketone 6 The oxidation step is based on a catalytic variant using TPAP.13... 

Gaseous oxygen can be employed, instead of NMO, as secondary oxidant in TPAP oxidations. This environment-friendly secondary oxidant, although not used routinely in synthetic organic laboratories, is very attractive for the industrial point of view and is the subject of active research, both in combination with TPAP68 and with several forms of supported perruthenate.69... 

Primary alcohols possess a substantially less crowded environment than secondary ones. Thus, in the absence of dominant electronic factors, many oxidants tend to react quicker with primary alcohols. These include many common oxidants, like TPAP,1 PCC,2 Parikh-Moffatt,3 Dess-Martin,4 IBX5 and Swern,6 that are sometimes able to perform selective oxidations of primary alcohols in useful yields, regardless of the fact that they were not devised for this purpose. 

Overman used TPAP for oxidation which co-reagent is necessary ... 

The readily available 2,3,4,6-fefra-O-benzyl-D-glucopyranose (11) can be used for the synthesis of both nojirimycin (1) and 1-deoxynojirimycin (2) (Schemed).It was treated with EtSH to furnish 12, which was oxidized to the corresponding ketone 13 using TPAP, while the Swern oxidation method failed to produce 13. Treatment of 13 with mercury(ll) salts in the presence of methanol followed by treatment with hydroxylamine hydrochloride in the presence of pyridine afforded the oxime 14 in 73% yield. Treatment of 14 with LiAlH4 in diethyl ether followed by N-protection of the resulting diastereomeric mixture of amines with di-rert-butyl dicarbonate furnished 15 and 16 in 65 and 15% yield, respectively. Pearlman s catalytic hydrogenation of 15 over palladium hydroxide in ethanol followed by treatment of the resulting tetrol with SO2 in water furnished the sulfonic acid 17 in 80% yield. Conversion of 17 into 1 was accomplished by treatment with Dowex 1X2 (OH ) resin. 

The synthesis of 4 involves ten initial steps to achieve alcohol 54 from tyrosine (16% overall yield) and pursues with the change of the alkyl side chain on the phenolic hydroxyl group (Scheme 46). Thus, O-demethylation of 54 followed by prenylation and treatment of the resulting lactam with LiAlH4 gaves azaspiranic compound 149. Protection of the secondary amine and oxidation of both alcohols using TPAP/NMO lead to the keto aldehyde 150. Treatment of the latter with Cd/Pb couple [78] allows the deprotection of the secondary amine as well as the cyclization process to provide (+)-TAN1251C (4). 

A very mild oxidative transformation of nitro compounds into ketones using tetrapropylam-monium perruthenate (TPAP) has been developed. A stoichiometric amount of TPAP in the presence of A-methylmorpholine A-oxide (NMO) and 4 A molecular sieves (MS).18a As the reaction conditions are neutral and mild, this method is compatible with the presence of other sensitive functionalities (Eq. 6.11). This transformation can be carried out with 10 mol% of TPAP and 1.5 equiv of NMO in the presence of potassium carbonate, 4 A MS, and silver acetate (Eq. 6.12).18b... 

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. 

---