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
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
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DOI：
10.1021/ja010654n
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发表时间：
2001-07-18
影响因子：
15
通讯作者：
Shibasaki, M
中科院分区：
文献类型：
--
作者：
Takamura, M;Funabashi, K;Shibasaki, M
描述了第一个催化对映选择性 Reissert 型反应的全部细节。利用路易斯酸-路易斯碱双功能催化剂5或6（9 mol%），以57%至99%的收率和54%至96%的ee得到Reissert产物。富电子的喹啉比缺电子的底物产生更好的产率和对映选择性。动力学研究表明，反应应通过决定速率的酰基喹啉鎓形成，然后是氰化物的攻击来进行。催化剂不利于第一个限速步骤；然而，它极大地促进了第二氰化步骤。该反应成功应用于有效催化不对称合成有效的 NMDA 受体拮抗剂 (-)-L-689,560。关键步骤是使用喹啉 If 的 Reissert 型反应的一锅法。然后立体选择性还原所得烯胺 2f。此步骤使用1mol%的6，得到Ley中间体20，收率91%，ee 93%。经过10次操作（包括重结晶）得到对映体纯的目标化合物，总收率47%。此外，将5固定到JandaJEL上，所得固体负载催化剂11以与均相6相当的产率提供20，但对映选择性稍低。
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 If. followed by stereoselective reduction of the resulting enamine 2f. This step gave the Ley 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, 5 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.