同济大学郑生财团队报道了轴向手性β-芳基卟啉铱配合物，催化N-甲基叔胺中C(sp³) -H键的对映选择性烷基化。相关研究成果发表在2024年11月27日出版的《美国化学会杂志》。

在具有挑战性的底物中，如N-甲基未阻断的芳香族和非失活的脂肪族叔胺，实现了对映选择性卡宾插入伯C（sp³）-H键的微调，其中空间要求高的β-轴向手性铱卟啉催化剂起着至关重要的作用。这种与重氮化合物的伯C（sp³）-H烷基化反应，以高产率提供了一系列具有优异对映选择性的β-手性叔胺。

值得注意的是，该方案成功应用于手性荷包牡丹碱的后修饰，产生了具有高非对映选择性的所需衍生物。

这种方法为具有N-甲基手柄的手性生物碱天然产物的立体发散衍生铺平了道路。此外，基于氘实验和通过HRMS分析鉴定的阳离子铱物种，提出了反应机理。

附：英文原文

Title: Enantioselective Alkylation of Primary C(sp3)–H Bonds in N-Methyl Tertiary Amine Enabled by Iridium Complex of Axially Chiral β-Aryl Porphyrins

Author: Shanshan Yuan, Sheng-Yu Li, Xiao-Ming Zhao, Ya-Zhou Lin, Sheng-Cai Zheng

Issue&Volume: November 27, 2024

Abstract: A fine-tuning of enantioselective carbene insertion into primary C(sp3)–H bonds has been realized in challenging substrates, such as N-methyl unblocked aromatic and non-deactivated aliphatic tertiary amines, in which sterically demanding β-axially chiral iridium porphyrin catalysts play a crucial role. This primary C(sp3)–H alkylation with diazo compounds affords a series of β-chiral tertiary amines in high yields with excellent enantioselectivities. Notably, the protocol was successfully applied to the postmodification of chiral bicuculline, yielding the desired derivative with high diastereoselectivity. This approach paves a facile way for the stereodivergent derivation of chiral alkaloid natural products featuring an N-methyl handle. In addition, a mechanism for the reaction was proposed based on deuterium experiments and an identified cationic iridium species via HRMS analysis.

DOI: 10.1021/jacs.4c12449

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c12449