Rhodium-catalyzed atropodivergent hydroamination of alkynes by leveraging two potential enantiodetermining steps

A pair of enantiomers is known to have different biological activities. Two catalysts with opposite chirality are nearly always required to deliver both enantiomeric products. In this work, chiral rhodium(III) cyclopentadienyl complexes are repurposed as efficient catalysts for enantiodivergent and atroposelective hydroamination of sterically hindered alkynes. Products with opposite chirality have been both obtained using the same or closely analogous chiral catalyst in good efficiency and excellent enantioselectivity, and the enantiodivergence was mainly enabled by an achiral carboxylic acid and its silver salt. Mechanistic studies revealed the origin of the enantiodivergence ascribable to the switch of the enantiodetermining step (alkyne insertion versus protonolysis) under acid control, which constitutes a previously unidentified working mode of enantiodivergence by leveraging two elementary steps.