Efficient desymmetrization of meso-cis-1,2-cyclohexanedimethanol with differentiation between diastereotopic and enantiotopic C-H bonds by (-)-sparteine-mediated deprotonation

The deprotonation of a dicarbamate prepared from cis-1,2-cyclohexanedimetha nol by sec-butyllithium/(-)-sparteine proceeds with efficient selection bet ween the enantiotopic branches and their diastereotopic protons with high p reference for the pro-S proton at the R branch to afford the intermediate, configurationally stable lithium compound as a single diastereomer. Trappin g of this intermediate by electrophiles (DOMe, CO2, CH3I, Me3SiCl, or R3SnC l) takes place with retention of the configuration to yield highly enantiom erically and diastereomerically enriched substitution products, which are e asily converted to diols, to anellated tetrahydrofurans, or to gamma-lacton es. The chiral base is also capable of efficient kinetic resolution of the racemic alpha-deuterated starting material, by the utilization of an extrao rdinarily high kinetic H/D isotope effect within the deprotonation step. Th e, presumably first example of the kinetic resolution of a racemic stannane by lithiodestannylation, utilizing methyllithium/(-)-sparteine, is reporte d.