Development of catalytic asymmetric 1,4-addition and [3 + 2] cycloaddition reactions using chiral calcium complexes.
Catalytic asymmetric 1,4-addition and [3 + 2] cycloaddition reactions using chiral calcium species prepared from calcium isopropoxide and chiral bisoxazoline ligands have been developed. Glycine Schiff bases reacted with acrylic esters to afford 1,4-addition products, glutamic acid derivatives, in high yields with high enantioselectivities. During the investigation of the 1,4-addition reactions, we unexpectedly found that a [3 + 2] cycloaddition occurred in the reactions with crotonate derivatives, affording substituted pyrrolidine derivatives in high yields with high enantioselectivities. On the basis of this finding, we investigated asymmetric [3 + 2] cycloadditions, and it was revealed that several kinds of optically active substituted pyrrolidine derivatives containing contiguous stereogenic tertiary and quaternary carbon centers were obtained with high diastereo- and enantioselectivities. In addition, optically active pyrrolidine cores of hepatitis C virus RNA-dependent polymerase inhibitors and potential effective antiviral agents have been synthesized using this [3 + 2] cycloaddition reaction. NMR spectroscopic analysis and observation of nonamplification of enantioselectivity in nonlinear effect experiments suggested that a monomeric calcium species with an anionic ligand was formed as an active catalyst. A stepwise mechanism of the [3 + 2] cycloaddition, consisting of 1,4-addition and successive intramolecular Mannich-type reaction was suggested. Furthermore, modification of the Schiff base structure resulted in a modification of the reaction course from a [3 + 2] cycloaddition to a 1,4-addition, affording 3-substituted glutamic acid derivatives with high diasterero- and enantioselectivities.
Tsubogo
Tetsu
T
Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Saito
Susumu
S
Seki
Kazutaka
K
Yamashita
Yasuhiro
Y
Kobayashi
Shu
S
D000596:Amino Acids / Q000737:chemistry; D002118:Calcium / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008673:Metals, Alkaline Earth / Q000737:chemistry; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry; D013237:Stereoisomerism
D000596:Amino Acids; D008024:Ligands; D008673:Metals, Alkaline Earth; D010080:Oxazoles; C064210:oxazolidine; D002244:Carbon; D002118:Calcium