Chiral modification of adamantane

Abstract

We have developed an efficient methodology for the preparation of optically active adamantane derivatives. Thus, enantiomerically enriched (> 96% ee) 1,2,5- and 1,3,4- substituted adamantanes were constructed starting from the common meso symmetric 7-methylidenebicyclo[3.3.1]nonan-3-one by employing either an asymmetric aldol reaction or the kinetic resolution under Sharpless asymmetric epoxidation condition for the enantiomerization steps, and the following titanium(IV) chloride mediated cyclization. The utility of the methodology has been demonstrated by synthesizing pharmaceutically attractive chiral α-adamantyl-α-amino acids.