Efficient Domino Process Based on the Catalytic Generation of Non-Metalated, Conjugated Acetylides in the Presence of Aldehydes or Activated Ketones

• Published in: Chemistry : a European journal 2003-07, Vol.9 (13), p.3122-3131
• Main Authors: Tejedor, David, García-Tellado, Fernando, Marrero-Tellado, José Juan, de Armas, Pedro
• Format: Article
• Language: English
• Subjects: acetylides; Aldehydes - chemistry; Aldehydes - metabolism; autocatalysis; C-C coupling; Catalysis; conjugation; domino reactions; Ketones - chemistry; Ketones - metabolism
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200204579

The extremely mild and highly efficient catalytic generation of non‐metalated, conjugated acetylides is reported. These acetylides are used to generate enol‐protected functionalized propargylic alcohols 1, 1,3‐dioxolane compounds 2, or 3,4,5‐trisubstituted 4,5‐dihydrofurans 4 through serial multibond‐forming processes. The method calls for a nucleophile (a tertiary amine or phosphine) as a chemical activator, a conjugated terminal acetylene as the acetylide source, and an aldehyde or activated ketone as the electrophilic partner. The chemical outcome of this process depends on the nature of the nucleophile, the temperature, stoichiometry and solvent, and it can be tailored selectively by the appropriate choice of the experimental conditions. En este trabajo se describe un método muy suave y eficiente para la generación catalítica de aniones acetiluro conjugados en ausencia de metales. Estos aniones acetiluros pueden generar selectivamente, mediante un proceso dominó catalítico, alcoholes propargílicos protegidos en la forma de su enol éter del tipo 1, compuestos 1,3‐dioxolánicos 1,2,4‐trisustituidos del tipo 2 o compuestos 4,5‐dihdrofuranos 3,4,5‐trisustituidos del tipo 4. El método requiere un nucleófilo como iniciador químico (una amina o fosfina terciaria), un acetileno conjugado como fuente de aniones acetiluro y un aldehído o cetona activada como especie electrofílica. La distribución de los productos depende marcadamente de la naturaleza del nucleófilo, la temperatura, la estequiometría y el tipo de disolvente utilizado, y puede ser dirigida selectivamente mediante la correcta elección de las condiciones experimentales. Highly functionalized compounds that could generate diversity in combinatorial libraries and in the development of multicomponent transformations are produced by the title reaction. The chemical outcome of the reaction can be tailored at will to give selectively enol‐protected functionalized propargylic alcohols 1, 3,4,5‐trisubstituted dihydrofurans 2, or 1,2,4‐trisubstituted 1,3‐dioxolanes 3. A mechanism is postulated to explain the experimentally observed influence of the nucleophile strength, temperature, and stoichiometry on the kinetic course of the process.