Zhang Shaochen, Del Pozo Juan, Romiti Filippo, Mu Yucheng, Torker Sebastian, Hoveyda Amir H
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA.
Supramolecular Science and Engineering Institute, University of Strasbourg, 67000 Strasbourg, France.
Science. 2019 Apr 5;364(6435):45-51. doi: 10.1126/science.aaw4029.
Accessing enantiomerically enriched amines often demands oxidation-state adjustments, protection and deprotection processes, and purification procedures that increase cost and waste, limiting applicability. When diastereomers can be formed, one isomer is attainable. Here, we show that nitriles, largely viewed as insufficiently reactive, can be transformed directly to multifunctional unprotected homoallylic amines by enantioselective addition of a carbon-based nucleophile and diastereodivergent reduction of the resulting ketimine. Successful implementation requires that competing copper-based catalysts be present simultaneously and that the slower-forming and less reactive one engages first. This challenge was addressed by incorporation of a nonproductive side cycle, fueled selectively by inexpensive additives, to delay the function of the more active catalyst. The utility of this approach is highlighted by its application to the efficient preparation of the anticancer agent (+)-tangutorine.
获取对映体富集的胺类通常需要进行氧化态调整、保护和脱保护过程以及纯化程序，这会增加成本和浪费，限制了其适用性。当可以形成非对映异构体时，其中一种异构体是可以得到的。在此，我们表明，腈类在很大程度上被认为反应活性不足，但通过碳基亲核试剂的对映选择性加成以及所得酮亚胺的非对映发散还原，可以直接转化为多功能无保护的高烯丙基胺。成功实施需要同时存在竞争性的铜基催化剂，且形成较慢、反应活性较低的催化剂先起作用。通过引入一个由廉价添加剂选择性供能的非生产性侧循环来延迟活性较高催化剂的作用，解决了这一挑战。这种方法的实用性通过其在高效制备抗癌剂（+）-唐古特宁中的应用得到了突出体现。
