The pinacol rearrangement is essentially a dehydration reaction of an alcohol, specifically a diol. The following is an example of a pinacol rearrangement in which the (R,R)-diol (TBDMS is tert-butyldimethylsilyl) was allowed to react with 2,2 dimethylpropane (2,2-DMP) in the presence of boron trifluoride etherate at room temperature. This particular reaction was done in order to attain the acetone derivative.
Interestingly, instead of retaining its chirality, the product of the pinacol arrangement actually resulted in a racemic mixture. Subsequent derivatives of this product eventually yield benzophenone (hydroxyphenstatin), which, biologically, is a potent antitumor and antimitotic agent. Accordingly, hydroxyphenstatin has also been proven to inhibit tubulin assembly.
The above reaction shows an epimeric steroid alcohol being converted by a catalyst of ruthenium and aluminum oxide to a racemic mixture of 17-estradiol 3-methyl ether and a ketone. The racemic mixture is formed by converting the beta version of the ether, where the hydroxyl group is on the top of the ring, to the alpha version of the ether, where the hydroxyl group is underneath the ring. The reaction is stopped when the amount of alpha ether is roughly equivalent to the amount of beta ether. In the notation used, the wavy line between the hydroxyl group and the ether shows that the hydroxyl group can be in either the front or the back of the molecule.
However, a ketone can be produced instead of the alpha ether when the alcohol is oxidized. Because the purpose of the reaction is to racemize the ether, this ketone is an unwanted side product. To prevent oxidation, toluene at 100 C is used as a solvent. The chemical properties of toluene slow the formation of the ketone so that at temperatures around 100 C, the yield of the racemic mixture is about 54%. Any ketone that does form can be separated from the ether by flash chromatography. This reaction is a good way to racemize the ether efficiently and inexpensively; it was traditionally synthesized at a much higher cost.
D,L-1,2,4-butanetriol can be made in two different ways; the first way is commercial synthesis through reduction of esterified D,L-malic acid with sodium borohydride, NaBH4, while the second way involves microbes. The latter method was the focus of the journal article. Nitration of racemic D,L-1,2,4-butanetriol results in D,L-1,2,4-butanetriol trinitrate, a compound that is the energetic equivalent of nitroglycerin, but is less shock sensitive, more thermally stable, and less volatile. One of the final steps in the synthesis of D, L-1,2,4-butanetriol via microbes is the reduction of a racemic mixture of D,L-3,4-dihydroxybutanal (aldehyde), to the final alcohol product, as seen in the reaction below. The catalyst for the reaction is dehydrogenase from E. coli.
