Pinacol and Semipinacol Rearrangements

acyl X = Cl, Br, I, SR, OTs, OMs, N2 Tiffeneau-Demjanov rearrangement)] orotic acid H2SO4, HCIO4, H3PO, 

TsOH Lewis acid BF3 OEt2, TMSOTf mild conditions LiCI04/THF/CaC03, EtsAI/DCM, Et2AICI/DCM, etc. 

The first step of the process is the protonation of one of the hydroxyl groups, which results in the loss of a water molecule to give a carbocation intermediate. This intermediate undergoes a / f,27-shift to give a more stable carbocation that upon the loss of proton gives the product. The pinacol rearrangement was shown to be exclusively intramolecular, and both inversion and retention were observed at the migrating center. 

The total synthesis of (+)-furoscrobiculin B, a lactarane sesquiterpene isolated from basidiomycetes of mushrooms, was accomplished in the laboratory of H. Suemune and K. Kanematsu using a furan ring transfer reaction and a semipinacol rearrangement as key steps. The secondary hydroxyl group of the tricyclic c/s-vicinal diol substrate was converted to the corresponding tosylate that in situ underwent a ring-expansion reaction to afford an azulenofuran in good yield. 

Pettit and co-workers converted a highly substituted frans-stilbene derivative to the strong cancer cell growth inhibitor and antimitotic agent hydroxyphenstatin. The key step of the synthesis was a BFs-OEta-catalyzed pinacol rearrangement of an optically active vicinal diol to afford a substituted diphenylacetaldehyde in racemic form. From this key intermediate, several derivatives were prepared in addition to the target molecule. 

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CHAPTER 1 PINACOL AND SEMIPINACOL REARRANGEMENTS IN TOTAL SYNTHESIS... 

A new semipinacol rearrangement mediated by Sn(IV) was proposed by Bates and to explain the formation of 579 from 578 (equation 256). As stated by the authors, the mechanism of formation of 579 most likely involves an intermediate hydroxylamine 580 (equation 257). Nucleophilic addition of the hydroxylamine to the ketonic carbonyl leads to 581, which may undergo a tin-mediated pinacol-type rearrangement with preferred migration of the phenyl substituent to produce amide 582. 

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