State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, P. R. China.
Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing, 100084, P. R. China.
Angew Chem Int Ed Engl. 2021 Aug 2;60(32):17608-17614. doi: 10.1002/anie.202104788. Epub 2021 Jun 30.
The enantioselective aza-Diels-Alder reaction is efficient for constructing chiral tetrahydropyridines, but the catalytic asymmetric aza-Diels-Alder reaction of ketimines with unactivated dienes is still a challenging topic. Herein, guided by computational screening, a highly enantioselective aza-Diels-Alder reaction of 2-aryl-3H-indol-3-ones with unactivated dienes was realized by using a B(C F ) /chiral phosphoric acid catalyst system under mild conditions. The reaction has a broad scope with respect to both aza-Diels-Alder reaction partners and hence offers rapid access to an array of tetrahydropyridine derivatives with pretty outcomes (up to 99 % yield, >20:1 dr and 98:2 er). The reaction is very efficient: lowering catalyst loadings for the model reaction to 0.1 mol %, enantioselectivity is still maintained. The synthetic utility was confirmed by transformations of the products. DFT calculations provide convincing evidence for the interpretation of stereoselection.
对映选择性氮杂-Diels-Alder 反应是构建手性四氢吡啶的有效方法，但酮亚胺与非活化二烯的催化不对称氮杂-Diels-Alder 反应仍然是一个具有挑战性的课题。在此，在计算筛选的指导下，通过使用 B(C 6 F 5 ) 3 /手性磷酸催化剂体系，在温和条件下实现了 2-芳基-3H-吲哚-3-酮与非活化二烯的高对映选择性氮杂-Diels-Alder 反应。该反应对氮杂-Diels-Alder 反应的反应物具有广泛的范围，因此可以快速获得一系列具有良好结果的四氢吡啶衍生物（产率高达 99%，dr 大于 20:1，ee 大于 98:2）。该反应非常高效：将模型反应的催化剂负载量降低至 0.1 mol%，对映选择性仍然保持。通过产物的转化证实了其合成实用性。DFT 计算为立体选择性的解释提供了令人信服的证据。
