Highly diastereoselective type-I IMDA reaction forming medium-sized macrolactones

Structure: see text] Intramolecular Diels-Alder (IMDA) reactions of 2-pyrones containing an alkyne tether occur with remarkably high diastereofacial selectivity to provide medium-sized macrolactones. Because of the strain in the alkyne-tethered macrocyclic system, a single methyl group in the tether provides sufficient conformational bias to generate medium-sized macrocycles with unusually high selectivity.