Direct Umpolung Morita–Baylis–Hillman like α‐Functionalization of Enones via Enolonium Species

• Published in: Angewandte Chemie International Edition 2020-08, Vol.59 (35), p.15171-15175
• Main Authors: Arava, Shlomy, Santra, Sourav K., Pathe, Gulab K., Kapanaiah, Raja, Szpilman, Alex M.
• Format: Article
• Language: English
• Subjects: Acetic acid; Ammonium; Chemical reactions; Cross coupling; Diketones; enones; hypervalent iodine; Intermediates; Iodine; ketones; Lewis acid; Morita–Baylis–Hillman; Pyridines; Species; umpolung
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202005286

Herein we report on the umpolung of Morita–Baylis–Hillman type intermediates and application to the α‐functionalization of enone C−H bonds. This reaction gives direct access to α‐chloro‐enones, 1,2‐diketones and α‐tosyloxy‐enones. The latter are important intermediates for cross‐coupling reaction and, to the best of our knowledge, cannot be made in a single step from enones in any other way. The proposed mechanism is supported by spectroscopic studies. The key initial step involves conjugate attack of an amine (DABCO or pyridine), likely assisted by hypervalent iodine acting as a Lewis acid leading to formation of an electrophilic β‐ammonium‐enolonium species. Nucleophilic attack by acetate, tosylate, or chloride anion is followed by base induced elimination of the ammonium species to give the noted products. Hydrolysis of α‐acetoxy‐enones lead to formation of 1,2‐diketones. The α‐tosyl‐enones participate in Negishi coupling reactions under standard conditions. The hypervalent iodine reagent PIDA in combination with a nucleophilic amine (DABCO or pyridine) induces α‐functionalization of enones with three different nucleophiles. The reaction is proposed to proceed through the umpolung of Morita–Baylis–Hillman type intermediates. The proposed mechanism is supported by spectroscopic studies that details the conversion of several reaction intermediates into products.