Can these be used to induce acetal ring closures? For example, when dealing with a molecule that has both a C=O functional group and an alkene as part of its structure and there is the possibility of creating a 5 or 6 membered ring through intramolecular -OH attack on the C=O ... can we just use the $\ce{OsO4}$ to create the diol and expect it to provide us sufficient acidity to catalyze ring closure?

Same question goes for meta-chloroperoxybenzoic acid.

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    $\begingroup$ It's not unusual for hydroxy-esters to cyclize and form a lactone especially if a 5- or 6-membered ring can be formed. With a diol (from osmium tetroxide) you might get a thermodynamically controlled mixture of products. M-chloroperoxybenzoic will produce an epoxide. Acid catalyzed opening of the epoxide could yield stereoisomers which could also lead to a mixture of possible lactones. $\endgroup$ – ron Oct 28 '14 at 21:58
  • $\begingroup$ @ron but will the osmium tetroxide be acidic enough to form an lactone? $\endgroup$ – Dissenter Oct 28 '14 at 22:06
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    $\begingroup$ Just a guess, but I would think so. If the lactone is thermodynamically more stable than the hydroxyl-ester, then closure should occur under neutral conditions. $\endgroup$ – ron Oct 28 '14 at 22:16

With osmium tetroxide, no it does not appear that dihydroxylation and acetalization can be done simultaneously. Usually dihydroxylation is carried out with catalytic osmium tetroxide with a stoichiometric amount of N-methylmorpholine N-oxide (NMO). The latter regenerates the Os(VIII) species necessary to carry out the dihydroxylation and results in the formation of N-methylmorpholine, which is a weak base. Without an acid available for catalysis, the acetalization does not occur. The sequence can be accomplished in "one-pot" however. In practice, you can monitor the progress of the dihydroxylation reaction. When it is deemed complete, add catalytic acid directly to the same reaction mixture, which allows the acetal formation.

Reference: 10.1016/j.tetlet.2012.02.045

Similarly, the overall transformation has been accomplished with mCPBA, but it's not clear if happens without any further intervention. In the referenced paper below, it's not entirely clear to me when the epoxide opens, because the procedure specifies that the epoxidation step is carried out with exclusion of water. It's likely that the epoxide is stable until addition of water, which opens the epoxide to the diol and then the acetalization can occur, catalyzed by the meta-chlorobenzoic acid byproduct from the epoxidation. In some cases, they simply isolate the epoxyketone as well.

Reference: 10.1002/ejoc.201101087

  • $\begingroup$ Can dihydroxylation also be carried out with OsO4 and HOOH? Prof never heard of NMO. $\endgroup$ – Dissenter Dec 5 '14 at 13:39
  • $\begingroup$ I think so. One advantage of NMO is that you can buy it as the pure compound, while peroxide has to be purchased as a solution. In my experience, the concentration of peroxide is not always reliable. $\endgroup$ – jerepierre Dec 5 '14 at 15:52

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