Organocatalyst based cross-catalytic system.

We present our design of a cross-catalytic system based on organocatalysis. The system features two organic reactions, namely a deprotection reaction of Fmoc protected proline and a Mannich reaction between acetone and dihydroisoquinoline. The products of these two reactions, proline and a tetrahydroisoquinoline, respectively, are capable of reciprocal reaction rate enhancement. Detailed kinetic studies of the system and seeding experiments support the cross-catalytic relationship in the reaction network.

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 ß-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 ß-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.