Your browser doesn't support javascript.
loading
Radical Chlorination of Non-Resonant Heterobenzylic C-H Bonds and High-Throughput Diversification of Heterocycles.
Golden, Dung L; Flynn, Kaitlyn M; Aikonen, Santeri; Hanneman, Christopher M; Kalyani, Dipannita; Krska, Shane W; Paton, Robert S; Stahl, Shannon S.
Afiliación
  • Golden DL; Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
  • Flynn KM; Present address: Chemical Process Development, Bristol Myers Squibb, 556 Morris Avenue, Summit, New Jersey 07901, United States.
  • Aikonen S; Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
  • Hanneman CM; Present address: Drug Substance Development Chemistry, GSK, 1250 Collegeville Road, Collegeville, Pennsylvania 19426, United States.
  • Kalyani D; Department of Chemistry, Colorado State University, 1301 Center Avenue, Ft. Collins, Colorado 80523, United States.
  • Krska SW; Present address: In Silico Discovery, Johnson & Johnson Innovative Medicine, 1400 McKean Road, Spring House, Pennsylvania 19477, United States.
  • Paton RS; Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
  • Stahl SS; Discovery Chemistry, Merck & Co., Inc., 126 East Lincoln Ave., Rahway, New Jersey 07065, United States.
Chem ; 10(5): 1593-1605, 2024 May 09.
Article en En | MEDLINE | ID: mdl-39108591
ABSTRACT
Site-selective functionalization of the heterobenzylic C(sp3)-H bonds of pyridines and related heteroaromatic compounds presents challenges associated with the basic nitrogen atom and the variable reactivity among different positions on the heteroaromatic ring. Methods for functionalization of 2- and 4-alkylpyridines are increasingly available through polar pathways that leverage resonance stabilization of charge build-up at these positions. In contrast, functionalization of 3-alkylpyridines is largely inaccessible. Here, we report a photochemically promoted method for chlorination of non-resonant heterobenzylic C(sp3)-H sites in 3-alkylpyridines and related alkylheteroaromatics. Density functional theory calculations show that the optimal reactivity reflects a balance between the energetics of the two radical-chain propagation steps, with the preferred reagent consisting of an N-chlorosulfonamide. The operationally simple chlorination protocol enables access to heterobenzylic chlorides which serve as versatile intermediates in C-H cross-coupling reactions between heteroaromatic building blocks and diverse oxidatively sensitive nucleophiles using high-throughput experimentation.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Chem Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Chem Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos