Allylic amines are important compounds commonly found in natural products, agrochemicals, and pharmaceuticals. Hydroamination of dienes and allenes using late-transition-metal catalysts affords allylic amines in a single, 100% atom-economic step. Alkynes may also be used as substrates in some cases via in situ isomerization to an allene, but this limits the substrate scope to alkyl-substituted alkynes. An alternative approach is hydroaminoalkylation, in which the α-C−H bond of an amine is added across a C−C unsaturation in atom-economic fashion. The hydroaminoalkylation of alkynes provides allylic amines directly, however previously only the stoichiometric reaction was known. Given our long-standing interest in the hydroaminoalkylation of alkenes using earth-abundant, early-transition-metal catalysts, the catalytic hydroaminoalkylation of alkynes was investigated. Using a tethered bis(ureate) zirconium catalyst, initial stoichiometric studies of model intermediates demonstrated the feasibility of the catalytic reaction, suggesting that the open steric environment imparted by the ligand helps facilitate the challenging steps involved. Subsequent catalytic experiments confirmed that various N-benzylanilines and internal alkynes could undergo hydroaminoalkylation to give α,β,γ-substituted allylic amines as the sole organic product. Critically, this work provides a platform from which activity, regioselectivity, and stereoselectivity can be improved for this new disconnection for making allylic amines.

Zirconium-catalyzed hydroaminoalkylation of alkynes for the synthesis of allylic amines

ACS Spring 2022

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