Yu H.-J, Shao C, Cui Z, Feng C.-G, * Lin G.-Q. * Shanghai Institute of Organic Chemistry,
P. R. of China
Highly Enantioselective Alkenylation of Cyclic α,β-Unsaturated Carbonyl Compounds
as Catalyzed by a Rhodium–Diene Complex: Application to the Synthesis of (
S)-Pregabalin and (–)-α-Kainic Acid.
Chem. Eur. J. 2012;
18: 13274-13278
Key words
pregabalin - kainic acid - Hayashi–Miyaura asymmetric conjugate addition - rhodium
catalysis - alkenyl trifluoroborates
Significance
Pregabalin (Lyrica®) is a lipophilic GABA analogue that is prescribed for the treatment
of epilepsy. This short, small-scale synthesis of pregabalin features a highly enantioselective
asymmetric conjugate addition of the alkenyl trifluoroborate B to the α,β-unsaturated lactam A catalyzed by a rhodium complex incorporating the chiral bicyclo[3.3.0]octa-2,5-diene
ligand L.
Comment
A further 17 examples of this new variant of the Hayashi–Miyaura asymmetric conjugate
addition reaction are reported using six α,β-unsaturated carbonyl substrates and
ten alkenyl trifluoroborates. The asymmetric conjugate addition was also applied
to the synthesis of the potent neuroexcitatory agent α-kainic acid (seven steps, 40% overall
yield).
