Secondary oxidants MCPBA

As soon as, it was learnt that oxoammonium salts, which are unstable compounds, are very efficient in the oxidation of alcohols, and that they can be generated in situ by treating catalytic TEMPO, or related compounds, with MCPBA acting as a secondary oxidant, it became apparent that other secondary oxidants would be more practical than MCPBA in Synthetic Organic Chemistry. MCPBA is a very energetic oxidant that reacts with many functionalities including alkenes and ketones. 

Nevertheless, Celia et al. have proved that employing MCPBA as secondary oxidant in TEMPO-mediated oxidations may have a number of advantages when a one-pot oxidation of an alcohol with a concurrent alkene epoxidation or a Baeyer-Villiger oxidation is desired.6 The use of MCPBA as a secondary oxidant in TEMPO-mediated alcohol oxidations was recently reviewed.7... 

Apart from sodium hypochlorite, a number of alternative secondary oxidants for TEMPO-mediated alcohol oxidations can be employed. These include cerium (IV) ammonium nitrate (CAN),24 trichloroisocyanuric acid (TCCA),25 oxone ,26 MCPBA,2,3,7 PhI(OAc)2,27 W-chlorosuccinimide,28 sodium bromite,29 electrooxidation,8,21 H5IO626 and a polymer-attached diacetoxybromide (I) complex.30... 

The known allylic alcohol 9 derived from protected dimethyl tartrate is exposed to Sharpless asymmetric epoxidation conditions with (-)-diethyl D-tartrate. The reaction yields exclusively the anti epoxide 10 in 77 % yield. In contrast to the above mentioned epoxidation of the ribose derived allylic alcohol, in this case epoxidation of 9 with MCPBA at 0 °C resulted in a 65 35 mixture of syn/anti diastereomers. The Sharpless epoxidation of primary and secondary allylic alcohols discovered in 1980 is a powerful reagent-controlled reaction.12 The use of titanium(IV) tetraisopropoxide as catalyst, tert-butylhydro-peroxide as oxidant, and an enantiopure dialkyl tartrate as chiral auxiliary accomplishes the epoxidation of allylic alcohols with excellent stereoselectivity. If the reaction is kept absolutely dry, catalytic amounts of the dialkyl tartrate(titanium)(IV) complex are sufficient. 

An oxidative rearrangement took place during the MCPBA epoxidation of the secondary allylic alcohol auraptenol, leading to the enal shown in equation (20). This reaction has been used in an approach to casegravol and in a synthesis of amottinin. The reason why the intermediate epoxy alcohol undergoes rearrangement in this case is not known beyond the possibility that the m-chlorobenzoic acid by-product could act as an acidic catalyst. 

Nitrones, C=N" (R)=0, are generated by the oxidation of N-hydroxyl secondary amines with 5% aq. NaOCl. ° Secondary amines, such as dibenzylamine, can be converted to the corresponding nitrone by heating with cumyl hydroperoxide in the presence of a titanium catalyst. Imines are oxidized to amides with mcpba and BF3 OEt2. ° ... 

Amine protection. Primary and secondary amines are protected as r-butylsulfonamides by reaction with f-BuS(=0)Cl followed by oxidation with MCPBA. These derivatives are stable to strong bases including those used for metallation. However, they are cleaved by acid. 

In a more recent paper Celia and McGrath report that alcohols can be oxidized in MCPBA in purified THF, with hydrochloric acid (10 mole %) as the only I litalyst. Yields of ketones are high (75-95%) for unhindered secondary alcohols, Iml significantly lower for even slightly hindered alcohols (borneol-> camphor,. . % yield). A further limitation is that the method is not suitable for acid-Neiisitive substrates. 

Sterically hindered hydrazonyloxides such as 80 were much more persistent, as would be expected if their main reaction is indeed C-C dimerization to a structure like 78. MCPBA oxidation of ketone hydrazones 81 yielded the hydrazonyloxide radicals as well, but they were stable for only a few hours in solution and no radical dimers could be isolated. When both R groups of the ketone were alkyl as in 82, no radicals were seen by ESR unless at least one of the groups was especially sterically demanding. Irradiation of 81 and 82 with t-Bu-OO-t-Bu, t-BuOOH and air gave the corresponding hydrazonyloxides but in low concentration and accompanied by secondary radical products. 

The final steps in the conversion of (-)-ll-methoxytabersonine to (-)-vindoline (Scheme 13.53) involved benzeneseleninic anhydride [(C6H5Se0)20j oxidation followed by a second oxidation with meta-chloroperbenzoic acid (MCPBA) in the presence of sodium bicarbonate (NaHCOs). Without isolation, but with adjustment of the pff, reductive A-methylation of the indoline was effected with formaldehyde (ff2CO) addition to the imine, followed by sodium cyanoborohydride (NaBHsCN) reduction. Finally, selective acetylation of the secondary hydroxyl necessary to produce (-)-vindoline (in the presence of the tertiary alcohol) was accomplished with acetic anhydride-containing sodium acetate. 

Figure 6.5 shows the oxidation of secondary and primary alcohols under ambient conditions by the NHPI/Co(OAc)2/MCBA system. Aromatic and cyclic alcohols afford the corresponding ketones in good to quantitative yields. Primary alcohols are also oxidized to carboxylic acids in good yields, although MCPBA (m-chloroperben-zoic add) is added instead of MCBA. Lauryl alcohol leads to lauric acid (66% yield). 

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