A silicon tether approach for addition of functionalized radicals to chiral alpha-hydroxyhydrazones: diastereoselective additions of hydroxymethyl and vinyl synthons

Stereocontrolled additions of hydroxymethyl and vinyl groups to chiral alpha-hydroxyhydrazones can be achieved by radical cyclizations using bromomethyl or vinyl radical precursors tethered via a temporary silicon connection. Tin-mediated 5-exo radical cyclization of alpha-hydroxyhydrazones using a silicon-tethered bromomethyl group, followed by oxidative removal of the tether, provides anti-2-hydrazino 1,3-diols in good yield. Tandem thiyl radical addition-cyclization of alpha-hydroxyhydrazones using a silicon-tethered vinyl group, followed by treatment with potassium fluoride, affords acyclic allylic anti-hydrazino alcohols in good yield. The thiyl addition-cyclization method has been successfully extended to the use of alpha,beta-dihydroxyhydrazones without prior protection or hydroxyl differentiation. Diastereoselection in both reaction types increases with increasing A values of the appended groups, consistent with prediction by the Beckwith-Houk model for stereocontrol in 5-hexenyl radical cyclizations.