Yuan Shanshan, Li Sheng-Yu, Zhao Xiao-Ming, Lin Ya-Zhou, Zheng Sheng-Cai
School of Chemical Science and Engineering, Tongji University, 1239 Siping Road, Shanghai, 200092 P.R. China.
J Am Chem Soc. 2025 Jan 8;147(1):51-56. doi: 10.1021/jacs.4c12449. Epub 2024 Nov 27.
A fine-tuning of enantioselective carbene insertion into primary C()-H bonds has been realized in challenging substrates, such as -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()-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 -methyl handle. In addition, a mechanism for the reaction was proposed based on deuterium experiments and an identified cationic iridium species via HRMS analysis.
在具有挑战性的底物中，如β-甲基未受阻的芳香族和未失活的脂肪族叔胺，实现了对映选择性卡宾插入一级C()-H键的微调，其中空间位阻较大的β-轴向手性铱卟啉催化剂起着关键作用。这种用重氮化合物进行的一级C()-H烷基化反应以高收率和优异的对映选择性提供了一系列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，以高非对映选择性得到所需衍生物。这种方法为具有β-甲基基团的手性生物碱天然产物的立体发散衍生提供了一条简便途径。此外，基于氘实验和通过高分辨质谱分析确定的阳离子铱物种，提出了该反应的机理。
