Find in Library

Five- and six-membered ring lactones and lactams are ubiquitous frameworks in various natural and synthetic molecules and are key building blocks in organic synthesis. Catalytic addition of an O-H or N-H bond across an unactivated C–C double bond is an appealing approach to rapidly access such highly valuable <i>N</i>- and <i>O</i>-containing skeletons in a waste-free and 100% atom efficient process. Herein, we report, for the first time, the efficient and high-yield cyclization of δ/ε-alkenoic acids and <i>N</i>-protected δ-alkenamides catalyzedby practical and easily accessible Lewis acid scandium(III) triflate under thermal and microwave conditions. The selectivity outcome of the reaction of δ/ε-alkenoic acids was dependent on the substitution patterns of the backbone chain and alkene moiety, leading to the exclusive formation of either the corresponding γ/δ-lactones via an <i>O</i>-selective cyclization or the Friedel–Crafts-type product by <i>C</i>-selective cyclization. An uncommon and rarely disclosed <i>O</i>-selective cyclization occurred preferentially or exclusively when <i>N</i>-protected δ-alkenamides were engaged in the reaction. The atom selectivity of the cyclization was unambiguously confirmed by single crystal X-ray crystallography.