Enantioselective Michael addition to α,β-unsaturated imides catalyzed by a bifunctional organocatalyst
Enantioselective Michael addition to α,β-unsaturated imides catalyzed by a bifunctional organocatalyst
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DOI：
10.1002/anie.200500459
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Takemoto, Y
中科院分区：
文献类型：
--
作者：
Hoashi, Y;Okino, T;Takemoto, Y
在1a（10mol%）存在下，尽管2与酰胺3a的共轭加成没有得到所需产物，但与N-酰基-1，3-恶唑烷酮3b [10 e]的相同反应在96小时后完成，得到迈克尔加成物4 b，产率为89%（表1，条目1和2）。4 b的对映体纯度通过HPLC分析显示为83%ee。为了增强与硫脲1a的氢键相互作用，我们使用带有环脲部分的N-酰基-1，3-咪唑烷酮3c作为迈克尔受体，但4c的产率和对映选择性都较差（59%，81%ee;表1，条目3）。与3c相反，N-酰基吡咯烷酮3d显示为2的良好受体，以93%产率提供具有最佳对映选择性（87%ee）的相应产物4d（表1，条目4）。使用N-酰基哌啶酮3e和无环酰亚胺3f进行迈克尔加成反应导致化学产率和对映选择性显著降低（表1，条目5和6）。另一方面，2与酰亚胺3g的共轭加成顺利进行，但对映选择性（84%ee）略低于3d（表1，条目7）。值得注意的是，在稀释条件下（0.1M甲苯溶液）与3d的相同反应将立体选择性提高至93%ee。
ature in the presence of 1a (10mol%). Although the conjugate addition of 2 with amide 3a gave no desired product, the same reaction with N-acyl-1, 3-oxazolidinone 3b [10e] was completed after 96 h to give the Michael adduct 4b in 89% yield (Table 1, entries 1 and 2). The enantiopurity of 4b was revealed to be 83% ee by means of HPLC analysis. In the hope of enhancing the hydrogen-bonding interaction with thiourea 1a, we employed N-acyl-1, 3-imidazolidinone 3c, which bears a cyclic urea moiety, as a Michael acceptor, but both the yield of 4c and enantioselectivity were poorer (59%, 81% ee; Table 1, entry 3). In contrast with 3c, N-acylpyrrolidinone 3d was revealed to be a good acceptor of 2, providing the corresponding product 4d in 93% yield with the best enantioselectivity (87% ee)(Table1, entry4). Use of N-acylpiperidinone 3e and acyclic imide 3 f for the Michael addition reaction resulted in a significant decrease in both chemical yield and enantioselectivity (Table 1, entries 5 and 6). On the other hand, the conjugate addition of 2 with imide 3g proceeded smoothly, but the enantioselectivity (84% ee) was somewhat lower than that with 3d (Table 1, entry 7). Notably, the same reaction with 3d under dilute conditions (0.1 m solution in toluene) improved the stereoselectivity up to 93% ee.