Base-Catalyzed Stereospecific Isomerization of Electron-Deficient Allylic Alcohols and Ethers through Ion-Pairing

• Published in: Journal of the American Chemical Society Vol. 138; no. 40; pp. 13408 - 13414
• Main Authors: Martinez-Erro, Samuel, Sanz-Marco, Amparo, Bermejo Gómez, Antonio, Vázquez-Romero, Ana, Ahlquist, Mårten S. G, Martín-Matute, Belén
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 12.10.2016
• Subjects: Allylic alcohol; Allylic ethers; Base catalyzed; Basic conditions; Catalysis; Catalysts; Computational investigation; Conjugate acid; Electron-deficient; Ethers; Ions; Isomerization; Isomers; Ketones; Organic Chemistry; organisk kemi; Transition metal catalysts; Transition metals
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.6b08350

A mild base-catalyzed strategy for the isomerization of allylic alcohols and allylic ethers has been developed. Experimental and computational investigations indicate that transition metal catalysts are not required when basic additives are present. As in the case of using transition metals under basic conditions, the isomerization catalyzed solely by base also follows a stereospecific pathway. The reaction is initiated by a rate-limiting deprotonation. Formation of an intimate ion pair between an allylic anion and the conjugate acid of the base results in efficient transfer of chirality. Through this mechanism, stereochemical information contained in the allylic alcohols is transferred to the ketone products. The stereospecific isomerization is also applicable for the first time to allylic ethers, yielding synthetically valuable enantioenriched (up to 97% ee) enol ethers.