Asymmetric Brønsted base-catalyzed aza-Michael addition and [3 + 2] cycloaddition reactions of N-ester acylhydrazones and enones,Organic Chemistry Frontiers

当前位置： X-MOL 学术 › Org. Chem. Front. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Asymmetric Brønsted base-catalyzed aza-Michael addition and [3 + 2] cycloaddition reactions of N-ester acylhydrazones and enones
Organic Chemistry Frontiers ( IF 4.6 ) Pub Date : 2022-10-18 , DOI: 10.1039/d2qo01527g
Bo Zhu ₁ , Huili Sun ₁ , Huihui Fan ₁ , Mengqi Wang ₁ , Fangyuan Guo ₁ , Yubing Zhai ₁ , Gongming Zhu ₁ , Junbiao Chang ₁

Affiliation

The formation of acyclic azomethine imine 1,3-dipoles via an N,N′-prototropic shift of hydrazones in the presence of Lewis acids, Brønsted acids and hydrogen bonding catalysts is a fundamental and powerful strategy for the assembly of chiral pyrazolidines. Despite the advances made in this realm, the ability to gain precise chemoselective control remains challenging. Herein, we report the first highly enantioselective Brønsted base-catalyzed aza-Michael addition and stepwise cascade [3 + 2] cycloaddition reactions between N-ester acylhydrazones and β-trifluoromethyl-α,β-unsaturated ketones. By employing an L-tert-leucine-derived urea-tertiary amine bifunctional catalyst, the reaction was modulated to generate either chiral acyclic amination products or chiral pyrazolidines bearing vicinal three stereocenters with excellent enantio- and diastereoselectivities. In terms of synthetic utility, the enantio-enriched aza-Michael addition derivatives can be readily transformed into 2-pyrazolines bearing a trifluoromethyl unit in good yields with excellent enantioselectivities. Moreover, the selected chiral linear acylhydrazone derivatives exhibited good biological specificity for the tumor cell line MCF-7.

中文翻译：

N-酯酰基腙和烯酮的不对称布朗斯台德碱催化氮杂迈克尔加成和[3 + 2]环加成反应

在路易斯酸、布朗斯台德酸和氢键催化剂存在下，通过腙的 N , N '-质子位移形成无环偶氮甲亚胺 1,3-偶极子是组装手性吡唑烷的基本且有效的策略。尽管在这一领域取得了进展，但获得精确化学选择性控制的能力仍然具有挑战性。在此，我们报道了N-酯酰基腙与 β-三氟甲基-α,β-不饱和酮之间的第一个高度对映选择性 Brønsted 碱催化氮杂迈克尔加成和逐步级联 [3 + 2] 环加成反应。通过采用L - tert-亮氨酸衍生的脲-叔胺双功能催化剂，该反应被调节以产生手性无环胺化产物或手性吡唑烷，其具有邻位三个立体中心，具有优异的对映选择性和非对映选择性。在合成效用方面，富含对映体的氮杂迈克尔加成衍生物可以很容易地转化为带有三氟甲基单元的 2-吡唑啉，产率高，对映体选择性优异。此外，所选择的手性线性酰基腙衍生物对肿瘤细胞系MCF-7表现出良好的生物学特异性。

更新日期：2022-10-18

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南