title: Catalytic enantioselective Reissert-type reaction: development and application to the synthesis of a potent NMDA receptor antagonist (-)-L-689,560 using a solid-supported catalyst.
abstract: Full details of the first catalytic enantioselective Reissert-type reaction are described. Utilizing the Lewis acid-Lewis base bifunctional catalyst 5 or 6 (9 mol %), the Reissert products were obtained in 57 to 99% yield with 54 to 96% ee. Electron-rich quinolines produced better yields and enantioselectivities than electron-deficient substrates. Kinetic studies indicated that the reaction should proceed via the rate-determining acyl quinolinium formation, followed by the attack of a cyanide. The catalyst does not facilitate the first rate-determining step; however, it strongly facilitates the second cyanation step. The reaction was successfully applied to an efficient catalytic asymmetric synthesis of a potent NMDA receptor antagonist (-)-L-689,560. A key step is the one-pot process using the Reissert-type reaction from quinoline 1f, followed by stereoselective reduction of the resulting enamine 2f. This step gave the key intermediate 20 in 91% yield with 93% ee, using 1 mol % of 6. The enantiomerically pure target compound was obtained through 10 operations (including recrystallization) in total yield of 47%. Furthermore, 6 was immobilized to JandaJEL, and the resulting solid-supported catalyst 11 afforded 20 in a comparable yield to the homogeneous 6, but with slightly lower enantioselectivity.
authors.affiliation: Contribution from the Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takamura
authors.forename: K
authors.initials: K
authors.lastname: Funabashi
authors.forename: M
authors.initials: M
authors.lastname: Kanai
authors.forename: M
authors.initials: M
authors.lastname: Shibasaki
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000378:metabolism; D002384:Catalysis; D004339:Drug Compounding / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis / Q000378:metabolism; D006859:Hydrogen; D019906:Nuclear Magnetic Resonance, Biomolecular; D011806:Quinolinium Compounds / Q000032:analysis; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
chemical_list: D000634:Aminoquinolines; D018691:Excitatory Amino Acid Antagonists; D011806:Quinolinium Compounds; D016194:Receptors, N-Methyl-D-Aspartate; C074617:4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline; D006859:Hydrogen