TPAP/NMO

Whereas treatment of ( )-29 with camphanic chloride achieves the selective esterification of the hindered C-9 hydroxyl group, the action of acetic anhydride on (+)- 29 results in the equally selective acetylation of the C-10 hydroxyl group It is not clear to what this discrepancy should be attributed, so we will not offer a rationalization here. This unexpected result is, however, most gratifying because TPAP-NMO oxidation27 of the remaining C-9 hydroxyl furnishes keto acetate 6 (88 % overall yield). You will note that the contiguous keto and acetate functions in 6 are both expressed in the natural product. 

The commonest solvent for TPAP in organic oxidations is CH Clj (DCM), normally in conjunction with 4 A powdered molecular sieves (PMS) to remove water formed during the oxidation. Addition of CH3CN, as in many Ru-catalysed oxidations, makes reactions with TPAP/NMO more effective [59], and occasionally CH3CN is used as the only solvent [159]. Ionic liquids, e.g. [emim](PF )/PMS [479] and [bmim](BF )/PMS [480] have been used with TPAP/NMO. It has also been used in supercritical CO [457]. 

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. 

Some lactol-to-lactone oxidations were effected by TPAP/NMO/PMS/CH Clj [498, 499], or TPAP/NMO/PMS/CH3CN [159]. The system RUCI3 or RuO / Na(Br03)/aq. M Na3(C03) generates [RuO ]" in aqueous solution and oxidised secondary alcohols to ketones in high yield (Table 2.2) [213]. Kinetics of the oxidation of benzhydrol and 9-fluorenol by TPAP/NMO/CH3CN/30°C were measured. 

The system RuCl3/Na(Br03)/aq. M Na COj [213] converted diols to acids while TPAP/NMO/PMS/CH3CN oxidised diols to lactones [119] TPAP/NMO/PMS/ CH3CI2 was used for diol to dione conversion for sensitive steroidal alcohols [503]. The reagent TPAP/NMO/PMS/CH Cl oxidised primary-secondary 1,4- and 1,5-diols to lactones (Fig. 2.19) [481]. 

The dehydrogenative coupling of primary alcohols to indoylamides was effected by TPAP/NMO/PMS/CH3CN, e.g. of 3-phenyl-1-propanol with pratosine and hippadine [504]. 

Primary nitro compounds RNO were oxidised to RCOOH (the Nef reaction e.g. nitroethane to acetic acid) [RuO ] from RuCl3/(Br03)7aq. M Na2(C03) activated primary aUcyl halides RCl to RCOOH and secondary alkyl halides were similarly oxidised to ketones [213]. Secondary nitro compounds were converted to ketones by TPAP/NM0/PMS/K3(C03)/CH3CN (c/ 5.6.4, Fig. 5.19) [514]. As part of the total synthesis of the natural product ( )-erythrodiene a nitro-alcohol intermediate was converted to the diketone by TPAP/NMO/PMS/CH Clj [127]. 

Epoxy alcohols were oxidised by TPAP/NMO/PMS/CH Cl without affecting the epoxy group Fig. 2.2 also illustrates the tolerance of the system to alkenes (Tables 2.1 and 2.2) [16]. 

The system TPAP/NMO/PMS/CH Cl oxidised many primary alcohols to aldehydes, e.g. as steps in the synthesis of natural products (cf. 2.1.3), and also for monosilylated alcohols [56], epoxyiodoalcohols [57], allylic alcohols [47, 58],... 

Fig. 2.1 Preferential oxidation by TPAP/NMO of a primary alcohol over a secondary alcohol group [47]...

For a synthesis of the anti-cancer drug taxol TPAP/NMO was used in three steps, two for oxidation of primary alcohols to aldehydes (by TPAP/NMO/PMS/ CHjClj) and one for a secondary alcohol to ketone (by TPAP/NMO/PMS/CHjClj-CHjCN) [66], cf. also [111] and for the SERCA inhibitor thapsigargin (two primary alcohol and one secondary alcohol oxidation steps) [112], This system was also used during synthesis of the cholesterol biosynthesis inhibitor 1233A [52], the antibiotic and anti-parasitic ionophore tetronasin [113, 114] and for the cytotoxic sponge alkaloids motopuramines A and B [115]. 

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