Ir-Catalyzed Regio- and Enantioselective Hydroalkynylation of Trisubstituted Alkene to Access All-Carbon Quaternary Stereocenters

The stereoselective construction
of all-carbon quaternary stereocenters,
especially acyclic ones, represents an important challenge in organic
synthesis. In particular, homopropargyl amides with a quaternary stereocenter
β to a nitrogen atom are valuable synthetic intermediates, which
could be transformed to diverse chiral structures through alkyne transformations.
However, highly enantioselective synthetic methods for homopropargyl
amides with a β quaternary stereocenter are extremely rare.
We report here unprecedented substrate-directed, iridium-catalyzed
enantioselective hydroalkynylations of trisubstituted alkenes to form
an acyclic all-carbon quaternary stereocenter β to a nitrogen
atom. The hydroalkynylation of enamide occurred with unconventional
selectivity, favoring the more hindered reaction site. Homopropargyl
amides with β-stereocenters were prepared in high regio- and
enantioselectivities. Combined experimental and computational studies
revealed the origin of the regio- and enantioselectivities.