HYDROXYL-DIRECTED CARBON-CARBON BOND FORMATION REACTIONS MEDIATED BY SAMARIUM(II) IODIDE

We have demonstrated that the configuration of the hydroxyl groups in the starting materials has some influence in controlling the stereochemical outcome of the SmI2-promoted reductive couplings. Generally the reaction proceeds in good yields and provides an efficient route to polyoxygenated molecules with high and reproducible stereochemical control. In all cases of the hydroxyl-directed reductive couplings, the observed stereochemistry in the reaction products can be predicted by assuming a cyclic ketyl radical intermediate on the basis of chelation to the Sm(lll) cation generated during the initial single-electron reduction of the carbonyl group with the hydroxyl group. The impact which this new methodology on synthetic organic chemistry has is clearly evident from its applicability to total synthesis, one notable example being (-)-grayanotoxin III, a unique tetracyclic diterpene.