Enantioselective Synthesis of Dihydro-isochromanones Using Hypervalent Iodine

Significance

Reported is an enantioselective ­oxidative lactonization of ortho-alkenylbenzoate 7 using chiral hypervalent iodines to afford 4-oxyisochroman-1-ones 8. A series of optically active ­lactate-derived aryl-λ^³-iodanes 1-6 were synthesized and analyzed by X-ray structure crystallog-raphy, which provided information on enantio­differentiation preferences (M. Fujita, Y. Ookubo, T. Sugimura Tetrahedron Lett. 2009, 50, 1298). After optimization, the iodine reagent 6 was found to give the highest ee value for the oxylactonization of 7 with endo selectivity leading to δ-lactones 8. The reaction was described only for AcOH ­(using BF₃˙OEt₂ as iodine reagent activator) and TsOH as nucleophiles. A plausible mechanism was proposed without evidence based on the syn selectivity observed. Studies were also carried out to understand the structural characteristics of ­reagents 1-6 in solution.