Cubane, a hexahedral hydrocarbon, can be converted into an asymmetric molecule with a minimum of three substituents. The resulting chiral cubane can be used as a pharmacophore or a chiral ligand. Starting from the cubane carboxamide, the 1,2,3‐substituted compound was synthesized by sequential ortho‐metalation. The 1,3,5‐substituted compound was synthesized by combining site‐selective halogenation and halogen‐metal exchange and the resulting racemate was subjected to enantiomeric resolution by HPLC.
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.
Three-component coupling between an alkyne, iodoarene, and bis(iodozincio)methane yields allylic zinc with a tetrasubstituted alkene moiety in the presence of a nickel catalyst. The reaction proceeds via aryl nickelation of the alkyne and subsequent cross-coupling with bis(iodozincio)methane. Meanwhile, the same combination in the presence of a palladium and cobalt catalyst gives tetrasubstituted alkenylzinc. The reaction proceeds via a palladium-catalyzed cross-coupling of iodoarene with bis(iodozincio)methane followed by a cobalt-catalyzed benzylzincation of alkyne.
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