上海师范大学赵宝国团队报道了羰基催化丙胺与α，β-不饱和酮的直接对映选择性α- c - h共轭加成。相关研究成果发表在2024年9月11日出版的《美国化学会杂志》。

由于炔丙基胺的低α-氨基C-H酸度和NH₂基团的亲核干扰，炔丙基胺与α，β-不饱和酮的直接不对称α-C-H共轭加成仍然是一个巨大的挑战。

研究人员利用一种具有苯-吡啶联芳基骨架和庞大酰胺侧链的新型吡哆醛作为羰基催化剂，实现了NH₂无保护炔丙基胺与α，β-不饱和酮的直接不对称α-C-H共轭加成反应。

加合物随后进行原位分子内环化，以高产率（高达92%）制备广泛的手性多取代1-吡咯啉，具有优异的非对映选择性和烯选择性（高达>20:1 dr和99%ee）。

该项工作展示了一种直接获得药学上重要的手性1-吡咯啉的方法，它还提供了一个令人印象深刻的例子，即通过仿生有机催化剂实现惰性C-H键的直接不对称官能化。

附：英文原文

Title: Direct Enantioselective α-C–H Conjugate Addition of Propargylamines to α,β-Unsaturated Ketones via Carbonyl Catalysis

Author: Ruixin Zhang, Jiwei Xu, Siqi Liu, Shibo Si, Jiayao Chen, Lingxiao Wang, Wen-Wen Chen, Baoguo Zhao

Issue&Volume: September 11, 2024

Abstract: Direct asymmetric α-C–H conjugate addition of propargylamines to α,β-unsaturated ketones remains a great challenge due to the low α-amino C–H acidity of propargylamines and the nucleophilic interference of the NH2 group. Utilizing a new type of pyridoxals featuring a benzene-pyridine biaryl skeleton and a bulky amide side chain as carbonyl catalyst, we have accomplished direct asymmetric α-C–H conjugate addition of NH2-unprotected propargylamines to α,β-unsaturated ketones. The adducts undergo subsequent in situ intramolecular cyclization, delivering a wide range of chiral polysubstituted 1-pyrrolines in high yields (up to 92%) with excellent diastereo- and enatioelectivities (up to >20:1 dr and 99% ee). This work has demonstrated a straightforward approach to access pharmaceutically important chiral 1-pyrrolines, and it has also provided an impressive instance of direct asymmetric functionalization of inert C–H bonds enabled by biomimetic organocatalysts.

DOI: 10.1021/jacs.4c09840

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c09840