Pinacol rearrangement enantioselectivity

The Prins-pinacol rearrangement was utilized during the first enantioselective total synthesis of briarellin diterpenes by L.E. Overman and co-workers. The cyclohexadienyl diol substrate was condensed with a (Z)-a,p-unsaturated aldehyde at low temperature in the presence of catalytic amounts of acid and MgS04 as dehydrating agent. The initially formed acetal was then exposed to 10 mol% of SnCU to afford the desired tetrahydroisobenzofuran as a single stereoisomer that was later converted to briarellin F. 

The enantioselective total synthesis of the polysubstituted tetrahydrofuran (-)-citreoviral, the unnatural enantiomer, was synthesized by L.E. Overman et al. The Prins-pinacol rearrangement of an allylic 1,2-diol with an unsymmetrical ketone proceeded with high stereoselectivity. The jb/s(trimethylsilyl)-1,2-diol was condensed with the dimethyl acetal of the unsymmetrical ketone in the presence of catalytic amounts of TMSOTf, which yielded a nearly 1 1 mixture of the corresponding acetal and rearrangement product. The acetal was converted to the desired tetrahydrofuran product upon exposure to tin tetrachloride. 

The thio-Prins-pinacol rearrangement was the key transformation in L.E. Overman s enantioselective total synthesis of (+)-shahamin K. Treatment of the dithioacetal substrate with DMTSF brought about the rearrangement, which gave rise to the c/s-hydroazulene core of the natural product. 

Paquette, LA., Lord, M.D., and Negri, J.T. (1993) Enantioselective synthesis of natural (+)-dactyloxene B and C by actuation of oxoniiun ion-initiated pinacol rearrangement. Tetrahedron Lett., 34, 5693-5696. 

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