Alkyl Cyclopropyl Ketones in Catalytic Formal [3 + 2] Cycloadditions: The Role of SmI 2 Catalyst Stabilization

• Published in: Journal of the American Chemical Society Vol. 146; no. 18; pp. 12799 - 12807
• Main Authors: Mansell, Jack I, Yu, Song, Li, Muze, Pye, Emma, Yin, Chaofan, Beltran, Frédéric, Rossi-Ashton, James A, Romano, Ciro, Kaltsoyannis, Nikolas, Procter, David J
• Format: Journal Article
• Language: English
• Published: United States 08.05.2024
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.4c03073

Alkyl cyclopropyl ketones are introduced as versatile substrates for catalytic formal [3 + 2] cycloadditions with alkenes and alkynes and previously unexplored enyne partners, efficiently delivering complex, sp -rich products. The key to effectively engaging this relatively unreactive new substrate class is the use of SmI as a catalyst in combination with substoichiometric amounts of Sm ; the latter likely acting to prevent catalyst deactivation by returning Sm to the catalytic cycle. In the absence of Sm , background degradation of the SmI catalyst can outrun product formation. For the most recalcitrant alkyl cyclopropyl ketones, catalysis is "switched-on" using these new robust conditions, and otherwise unattainable products are delivered. Combined experimental and computational studies have been used to identify and probe reactivity trends among alkyl cyclopropyl ketones, including more complex bicyclic alkyl cyclopropyl ketones, which react quickly with various partners to give complex products. In addition to establishing alkyl cyclopropyl ketones as a new substrate class in a burgeoning field of catalysis, our study provides vital mechanistic insight and robust, practical approaches for the nascent field of catalysis with SmI .