Epimerization, diastereoselective protonation

Similarly, the tricyclic trans-fused lactone 16 has been diastereoselectively methylated by the same method to give 17 in 97% yield15. The stereochemistry of the methylation was proved by converting 17 into /3-santonin (R = CH3 R1 = H). of known configuration. Protonation of the enolate derived from 17 is again completely diastereoselective and furnished the epimeric lactone 18 in 80% yield, which was converted into a-santonin (R = H R1 = CH3). 

The rate of epimerization of an a-stereogenic centre within a carbonyl-containing compound with several stereogenic centres depends on the acidity of the enolizable proton. Diastereoselectivity depends on kinetic and/or thermodynamic effects (reagent and substrate control)... 

In many cases various proton sources, solvents, auxiliaries, and conditions have been applied in order to obtain different diastereoselectivites from the protonation of nonstereogenic car-banion centers. However, only the tw o extreme diastereomeric product ratios are given in this section. In most experiments kinetically controlled protonation can be assumed. However, since the anionic substrate already carries one (or more) stereogenic center, selective equilibration at the newly formed stereogenic carbon - hydrogen center could increase the diastereoselec-tivity. Indeed, epimerization of this center is a valuable tool for diastereoselective synthesis, provided that the carbon-hydrogen bond is acidic enough (see enolates, Section 2.1.3.1). 

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