Synthesis of Sterically Congested 2,2′-Bi(Adamantyl)-Based Alcohol and Amines

Sterically congested chiral alcohol and amines have gained
tremendous
attention in the design of asymmetric catalysts. Herein, the synthesis
of a sterically congested bis-adamantane framework-based chiral alcohol,
(1R,2S,3S,4R)-4-(2-adamantyl)­adamantan-2-ol, and amine, (1R,2S,3S,4R)-4-(2-adamantyl)­adamantan-2-amine,
is described. Access to these sterically encumbered compounds is found
via the preparation of an enantioenriched 4-adamantyladamantan-2-one
intermediate, which was synthesized in 6 steps from adamantan-2-one.
The key step involved enzyme-catalyzed ester hydrolysis in giving
unsaturated alcohol with an enantiomeric excess of >95%. This adamantylidene
adamantanol was subjected to an acid-catalyzed intramolecular [1,4]
shift to give the key chiral intermediate without racemization. This
ketone intermediate was transformed into the target compounds via
reduction and reductive amination protocols.