Development of bifunctional organocatalysts and application to asymmetric total synthesis of naucleofficine I and II
Development of bifunctional organocatalysts and application to asymmetric total synthesis of naucleofficine I and II
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DOI：
10.1038/s41467-019-11382-8
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发表时间：
2019-07
影响因子：
16.6
通讯作者：
Yong-Hai Yuan;Xue Han;Fu-Ping Zhu;Jin‐Miao Tian;Fu‐Min Zhang;Xiao‐Ming Zhang;Y. Tu;Shao-Hua Wang-Shao-Hua-Wa
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文献类型：
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作者：
Yong-Hai Yuan;Xue Han;Fu-Ping Zhu;Jin‐Miao Tian;Fu‐Min Zhang;Xiao‐Ming Zhang;Y. Tu;Shao-Hua Wang-Shao-Hua-Wa
脯氨酸型有机催化剂已被有效地用于催化广泛的不对称转化;然而，仍有许多合成上有用且具有挑战性的转化仍然无法以不对称方式实现。本文设计、制备了一种含氟烷基和芳基磺酰胺官能团的螺环吡咯烷骨架手性双功能有机催化剂，并考察了其在3，4-二氢-β-咔啉与乙醛、酰卤和Wittig试剂的不对称Mannich/酰化/Wittig反应中的催化活性.结果，螺环吡咯烷三氟甲磺酰胺催化剂可以促进这种通用序列，如通过18个实施例所证明的，显示出优异的对映选择性（高达94%ee），以及中等至良好的产率（在3个步骤中高达54%）。作为实际应用，我们完成了乌藨子碱I（1a）和II（1b）的不对称全合成。
The proline-type organocatalysts has been efficiently employed to catalyze a wide range of asymmetric transformations; however, there are still many synthetically useful and challenging transformations that remain unachievable in an asymmetric fashion. Herein, a chiral bifunctional organocatalyst with a spirocyclic pyrrolidine backbone-derived containing fluoro-alkyl and aryl sulfonamide functionalities, are designed, prepared, and examined in the asymmetric Mannich/acylation/Wittig reaction sequence of 3,4-dihydro-β-carboline with acetaldehyde, acyl halides, and Wittig reagents. As a result, the spirocyclic pyrrolidine trifluoromethanesulfonamide catalyst can facilitate this versatile sequence as demonstrated by 18 examples displaying excellent enantioselectivity (up to 94% ee), as well as moderate to good yields (up to 54% over 3 steps). As a practical application, the asymmetric total synthesis of naucleofficine I (1a) and II (1b) in ten steps have been accomplished.