{"title":"饱和 N-杂环 C-H 键官能化用于烷基化 N-杂环合成的最新进展","authors":"Cameron H. M. Zheng, Laurel L. Schafer","doi":"10.1055/s-0043-1775377","DOIUrl":null,"url":null,"abstract":"<p>The prominence of saturated <i>N</i>-heterocycle motifs in pharmaceuticals is undeniable. Challenges associated with the alkylation of saturated <i>N</i>-heterocycle scaffolds to efficiently access new drug analogues are hampered by synthetically laborious routes. Stereocontrolled alkyl-substitutions onto saturated <i>N</i>-heterocycles are particularly difficult to access in high yields by traditional synthetic methods. Alternatively, C–H bond functionalization provides a new and powerful synthetic avenue by directly and selectively functionalizing/alkylating/ arylating the abundantly available C–H bonds of saturated <i>N</i>-heterocycles. This review highlights complementary methods for directly activating and functionalizing C–H bonds of saturated <i>N</i>-heterocycles chemo-, regio-, and or stereoselectively to access alkylated products. This synthetic challenge has required catalyst development to access useful <i>N</i>-heterocyclic building blocks or for late-stage functionalization. Early transition metal, late transition metal, photoredox, and electrochemical methods are discussed. The selective functionalization of α, β, and γ C–H bonds to form new C–C, C–N, C–O, and C–B bonds is presented.</p> <p>1 Introduction</p> <p>2 Early Transition Metal Catalyzed α-Alkylation</p> <p>3 Late Transition Metal Catalyzed α-Functionalization</p> <p>4 Photoredox-Catalyzed α-Functionalization</p> <p>5 Electrochemical α-Functionalization</p> <p>6 C–H Functionalization of β and γ C–H Bonds</p> <p>7 Conclusions/Outlook</p> ","PeriodicalId":501298,"journal":{"name":"Synthesis","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Recent Advances in Saturated N-Heterocycle C–H Bond Functionalization for Alkylated N-Heterocycle Synthesis\",\"authors\":\"Cameron H. M. Zheng, Laurel L. Schafer\",\"doi\":\"10.1055/s-0043-1775377\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The prominence of saturated <i>N</i>-heterocycle motifs in pharmaceuticals is undeniable. Challenges associated with the alkylation of saturated <i>N</i>-heterocycle scaffolds to efficiently access new drug analogues are hampered by synthetically laborious routes. Stereocontrolled alkyl-substitutions onto saturated <i>N</i>-heterocycles are particularly difficult to access in high yields by traditional synthetic methods. Alternatively, C–H bond functionalization provides a new and powerful synthetic avenue by directly and selectively functionalizing/alkylating/ arylating the abundantly available C–H bonds of saturated <i>N</i>-heterocycles. This review highlights complementary methods for directly activating and functionalizing C–H bonds of saturated <i>N</i>-heterocycles chemo-, regio-, and or stereoselectively to access alkylated products. This synthetic challenge has required catalyst development to access useful <i>N</i>-heterocyclic building blocks or for late-stage functionalization. Early transition metal, late transition metal, photoredox, and electrochemical methods are discussed. The selective functionalization of α, β, and γ C–H bonds to form new C–C, C–N, C–O, and C–B bonds is presented.</p> <p>1 Introduction</p> <p>2 Early Transition Metal Catalyzed α-Alkylation</p> <p>3 Late Transition Metal Catalyzed α-Functionalization</p> <p>4 Photoredox-Catalyzed α-Functionalization</p> <p>5 Electrochemical α-Functionalization</p> <p>6 C–H Functionalization of β and γ C–H Bonds</p> <p>7 Conclusions/Outlook</p> \",\"PeriodicalId\":501298,\"journal\":{\"name\":\"Synthesis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Synthesis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1055/s-0043-1775377\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Synthesis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1055/s-0043-1775377","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Recent Advances in Saturated N-Heterocycle C–H Bond Functionalization for Alkylated N-Heterocycle Synthesis
The prominence of saturated N-heterocycle motifs in pharmaceuticals is undeniable. Challenges associated with the alkylation of saturated N-heterocycle scaffolds to efficiently access new drug analogues are hampered by synthetically laborious routes. Stereocontrolled alkyl-substitutions onto saturated N-heterocycles are particularly difficult to access in high yields by traditional synthetic methods. Alternatively, C–H bond functionalization provides a new and powerful synthetic avenue by directly and selectively functionalizing/alkylating/ arylating the abundantly available C–H bonds of saturated N-heterocycles. This review highlights complementary methods for directly activating and functionalizing C–H bonds of saturated N-heterocycles chemo-, regio-, and or stereoselectively to access alkylated products. This synthetic challenge has required catalyst development to access useful N-heterocyclic building blocks or for late-stage functionalization. Early transition metal, late transition metal, photoredox, and electrochemical methods are discussed. The selective functionalization of α, β, and γ C–H bonds to form new C–C, C–N, C–O, and C–B bonds is presented.
1 Introduction
2 Early Transition Metal Catalyzed α-Alkylation
3 Late Transition Metal Catalyzed α-Functionalization