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Mechanistic Studies Yield Improved Protocols for Base-Catalyzed Anti-Markovnikov Alcohol Addition Reactions.
Luo, Chaosheng; Alegre-Requena, Juan V; Sujansky, Stephen J; Pajk, Spencer P; Gallegos, Liliana C; Paton, Robert S; Bandar, Jeffrey S.
Afiliação
  • Luo C; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
  • Alegre-Requena JV; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
  • Sujansky SJ; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
  • Pajk SP; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
  • Gallegos LC; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
  • Paton RS; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
  • Bandar JS; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
J Am Chem Soc ; 144(22): 9586-9596, 2022 06 08.
Article em En | MEDLINE | ID: mdl-35605253
The catalytic anti-Markovnikov addition of alcohols to simple alkenes is a longstanding synthetic challenge. We recently disclosed the use of organic superbase catalysis for the nucleophilic addition of alcohols to activated styrene derivatives. This article describes mechanistic studies on this reversible reaction, including thermodynamic and kinetic profiling as well as computational modeling. Our findings show the negative entropy of addition is counterbalanced by an enthalpy that is most favored in nonpolar solvents. However, a large negative alcohol rate order under these conditions indicates excess alcohol sequesters the active alkoxide ion pairs, slowing the reaction rate. These observations led to an unexpected solution to a thermodynamically challenging reaction: use of less alcohol enables faster addition, which in turn allows for lower reaction temperatures to counteract Le Chatelier's principle. Thus, our original method has been improved with new protocols that do not require excess alcohol stoichiometry, enable an expanded alkene substrate scope, and allow for the use of more practical catalyst systems. The generality of this insight for other challenging hydroetherification reactions is also demonstrated through new alkenol cyclization and oxa-Michael addition reactions.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estireno / Alcenos Tipo de estudo: Guideline / Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estireno / Alcenos Tipo de estudo: Guideline / Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article