Asymmetric Hydrogenation of 1,4,5,6-Tetrahydropyrazine-2-(N-tert-butyl)carboxamide Catalyzed by Trans-Chelating Chiral Diphosphine−Rhodium Complexes

Highly enantioselective hydrogenation of 1,4,5,6-tetrahydropyrazine-2-( N - tert -butyl)carboxamide ( 2 ) was accomplished by a rhodium complex coordinated with a chiral diphosphine TRAP ligand, which is possible to chelate to a transition metal atom in a trans-manner. Of particular interest is that ( R, R )-( S, S )- i -BuTRAP gave 97% ee of the corresponding piperazine-2-carboxylic acid derivative ( 3 ) with ( S ) configuration, while the hydrogenation with ( R, R )-( S, S )-MeTRAP−rhodium catalyst provided ( R )- 3 with up to 85% ee. 31 P NMR studies of behavior of i -Bu- and MeTRAP−rhodium catalysts during the reaction suggest that the asymmetric hydrogenation of 2 with TRAPs may involve two competitive reaction pathways, giving their respective enantiomeric products 3 .