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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

2001; American Chemical Society; Volume: 123; Issue: 28 Linguagem: Inglês

10.1021/ja010654n

1943-2984

Masahiro Takamura, Ken Funabashi, Motomu Kanai, Masakatsu Shibasaki,

Asymmetric Hydrogenation and Catalysis

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.