Stereoselective total synthesis of skew-tetramantane

Diamond’s elementary chiral constituent—skew-tetramantane—features extreme rigidity, stability and a precisely defined geometry, epitomizing the parent structure of a σ-helicene. While skew-tetramantane is naturally occurring in trace fractions in fossil fuels, efforts over several decades towards its selective synthesis remained unfruitful. With the recent advances in photocatalysis and transition metal catalysis to tame radical and carbene species, we have now devised a targeted total synthesis of skew-tetramantane by means of a stereoselective adamantalogous cage extension. A first cap attachment was effected by a photocatalytic Giese reaction, while remarkable regio-, diastereo- and enantiocontrol were achieved by an intramolecular C(sp3)−H insertion using Davies’ chiral rhodium catalysts. After a Buchner–Curtius–Schlotterbeck ring expansion and a stereoselective Mukaiyama hydration, the fusion to the adamantine skew-tetramantane structure was completed by an intramolecular C(sp3)−H insertion of a non-stabilized carbenoid. Here we show that this approach provides access to synthetic skew-tetramantane in isomerically pure form with σ-helicity defined by the catalyst, marking a selective pathway to higher diamondoids. skew-Tetramantane—diamond’s chiral core—previously only accessible from fossil fuels after elaborate separations, was selectively synthesized by a combination of visible-light photocatalytic reactions to modulate radical chemistry and catalyst-controlled C–H insertions. Operating under kinetic control, this stereoselective adamantalogous cage-extension strategy provides access to synthetic diamondoids beyond adamantane, diamantane and triamantane.