Scaffold Editing of Cubanes into Homocubanes, Homocuneanes via Cuneanes.

The selective synthesis of cage-type hydrocarbons through the editing of the highly symmetric molecule cubane can be anticipated as one of the efficient approaches. In this paper, we identify a catalyst that facilitates the efficient scaffold isomerization of cubanes into homocubanes. This approach, which involves the direct synthesis of homocubanol esters, is promising as a novel method for the synthesis of phenoxy bioisosteres. Additionally, we observed that the isomerization of 1,4-bis(acyloxymethl)cubane results in the generation of both D2 - and C2 -symmetrical bishomocubanes. The same catalyst was also applied to the isomerization of acyloxymethylcuneanes, producing homocuneanol esters.

Chiral Auxiliary-Directed Site-Selective Deprotonation of the Cubane Skeleton.

The first diastereoselective synthesis of trisubstituted cubanes was achieved using a chiral auxiliary. To establish chirality within the cubane skeleton, at least three substituents must be introduced at the appropriate positions. Ready conversion of cubane carboxylic acid to a chiral amide followed by sequential ortho-selective deprotonations and electrophilic trapping afforded the corresponding 1,2,3-trisubstituted cubanes with high diastereoselectivity. This route opens new possibilities for the preparation of enantio-enriched cubanes.