General Procedure for Parikh-Doering Oxidation

This oxidation presented a serious challenge, because of the tendency of the substrate to suffer dehydration, or oxidative breakage at the benzylic positions. It succeeded under Parikh-Doering conditions, provided that scrupously dry conditions are used, and the reaction of SO3 Py with DMSO precedes the interaction with the diol, in order to avoid the formation of a sulfate ester. Thus, the solution of SO3 Py in DMSO was prepared 5 min in advance of its use. The application of the closely related Albright-Goldman oxidation led to erratic yields, the diol acetate being the main side product. 

After considerable experimentation, it was found that the Parikh-Doering oxidation provides a good and reproducible yield. Under Swern conditions, yields are erratic with substantial quantities of a product, arising from opening of the epoxide by attack of a chloride ion being formed. PCC did not afford a good yield of alcohol. 

While the Parikh-Doering oxidation succeeds, a Swern oxidation produces chlorination at the activated 3-position of the indole.  

During the oxidation, an acid-catalyzed cyclization of the product by attack of the nitrogen atoms on the ketone, leading to three different aminals, must be avoided. A Parikh-Doering oxidation gives a good yield of the desired ketone, while PCC, Dess-Martin reagent and Jones oxidation deliver diverse amounts of aminals. 

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