摘要：State Key Laboratory of Natural andBiomimetic Drugs, Chemical Biology Center, School of Pharmaceutical Sciences,Peking University,
转自：康龙化成
Selective Nitrogen Insertion intoAryl Alkanes
ZhengZhang, Qi Li, Zengrui Cheng, Ning Jiao & Chun Zhang
State Key Laboratory of Natural andBiomimetic Drugs, Chemical Biology Center, School of Pharmaceutical Sciences,Peking University, China
—Nat.Commun. 2024, 15, 6016.
Recommended by Bing Han_MC3
KEY WORDS:skeletalediting (反应类型),nitrogen insertion (反应类型), arylalkanes (反应物), O-tosylhydroxylamine (反应物), C(sp2)–N, C(sp3)-N (成键类型);
ABSTRACT: Molecular structure-editingthrough nitrogen insertion offers more efficient and ingenious pathways for thesynthesis of nitrogen-containing compounds, which could benefit the developmentof synthetic chemistry, pharmaceutical research, and materials science. Substitutedamines, especially nitrogen containing alkyl heterocyclic compounds, are widelyfound in nature products and drugs. Generally, accessing these compoundsrequires multiple steps, which could result in low efficiency. In this work, amolecular editing strategy is used to realize the synthesis ofnitrogen-containing compounds using aryl alkanes as starting materials. Usingderivatives of O-tosylhydroxylamine asthe nitrogen source, this method enables precise nitrogen insertion into theCsp2- Csp3 bondof aryl alkanes. Notably, further synthetic applications demonstrate that thismethod could be used to prepare bioactive molecules with good efficiency andmodify the molecular skeleton of drugs. Furthermore, a plausible reactionmechanism involving the transformation of carbocation and imine intermediateshas been proposed based on the results of control experiments.
Background: Normalretrosynthetic analysis of N-containing heterocyclic compounds and this work:nitrogen atom insertion to extend the alkane ring (or chain)
Theeffects of different reaction conditions
Selectedsubstrate scope of selective nitrogen insertion
The proposed reaction mechanism
Prof.Jiao and his co-workers reported a reaction for realizing nitrogen insertion intoaryl alkanes.By employing a molecular editing strategy,this chemistry can expand the ring or lengthen thecarbon chain under ambient reaction conditions.Notably, this chemistry, which is compatible with various functionalgroups, hasbeen successfullyused to modify drug molecules and synthesize bioactive compounds.
来源：新浪财经
