Copper Hydride Catalysis for the Synthesis of Axially Chiral Allenes

Allenes, compounds containing two double bonds across three contiguous carbons, are versatile synthetic intermediates due to their substituent loading capacity and ability to generate one or more new stereogenic centers through axial-to-central chirality transfer. This structural motif is also present in over 150 natural products and a variety of bioactive molecules. Despite their prevalence and distinct reactivity, catalytic methods to access chiral 1,3-disubstituted allenes with high levels of selectivity from achiral starting materials remains a goal in chemical synthesis.

We have developed a mild and general strategy for the highly selective semi-reduction of prochiral 1,3-enynes. A diverse array of enantioenriched 1,3-disubstituted allenes are furnished in up to 98% yield and 99% enantioenrichment. This reaction is enabled by chiral copper hydride catalysts in the presence of water as a benign and abundant proton source. Additional applications of this method further illustrate the advantage of this simple protocol for the selective synthesis of mono-deuterated allenes and chiral 2,5-dihydropyrroles.