Chemoselective Ketone Synthesis by the Strontium-mediated Alkylation or Arylation of N,N-Dimethylamides or Urea

Ketone synthesis via the addition of organometallic reagents to amides has long been investigated. In many cases, it is necessary to control the solvent, reaction temperature, and adhere to strict nucleophile stoichiometry for each combination of amide and organometallic reagent. Strontium, with an electronegativity comparable to lithium but a larger ionic radius, may display high reactivity with the characteristics of monoalkylation. Here, we show that the monoalkylation of various N,N-dimethylamide derivatives with alkyl iodides to afford the ketones proceeds smoothly under generally mild temperature conditions. By this method, not only aromatic amides but also α-proton-bearing aliphatic amides were suitable substrates for ketone synthesis. In addition, we found that tetramethylurea, typically a poor electrophile, also reacted to afford benzophenone in good yield with excellent selectivity.

This is the peer reviewed version of the following article: N. Miyoshi, S. Kimura, S. Kubo, S. D. Ohmura, M. Ueno, Asian J. Org. Chem. 2020, 9, 1660., which has been published in final form at https://doi.org/10.1002/ajoc.202000389. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.