Catalytic asymmetric addition of Grignard reagents to alkenyl-substituted aromatic N-heterocycles.
Catalytic asymmetric conjugate addition reactions represent a powerful strategy to access chiral molecules in contemporary organic synthesis. However, their applicability to conjugated alkenyl-N-heteroaromatic compounds, of particular interest in medicinal chemistry, has lagged behind applications to other substrates. We report a highly enantioselective and chemoselective catalytic transformation of a wide range of β-substituted conjugated alkenyl-N-heteroaromatics to their corresponding chiral alkylated products. This operationally simple methodology can introduce linear, branched, and cyclic alkyl chains, as well as a phenyl group, at the β-carbon position. The key to this success was enhancement of the reactivity of alkenyl-heteroaromatic substrates via Lewis acid activation, in combination with the use of readily available and highly reactive Grignard reagents and a copper catalyst coordinated by a chiral chelating diphosphine ligand.
Stratingh Institute for Chemistry, 9747 AG Groningen, Netherlands.
Ravindra P
RP
Jumde
Stratingh Institute for Chemistry, 9747 AG Groningen, Netherlands.
Francesco
F
Lanza
Stratingh Institute for Chemistry, 9747 AG Groningen, Netherlands.
Marieke J
MJ
Veenstra
Stratingh Institute for Chemistry, 9747 AG Groningen, Netherlands. s.harutyunyan@rug.nl.
Syuzanna R
SR
Harutyunyan