Synthesis of (R)-3-Methylphthalide by Reductive Cyclization of a 2-Acylarylcarboxylate Using the Chiral Boronic Ester TarB-H and Sodium Borohydride

Background: Phthalides are pervasive benzolactone structural frameworks in nature and have a broad profile of biological activities. Catalytic asymmetric reduction with the in situ lactonization of 2-acylarylcarboxylate compounds is an efficient strategy for chiral phthalide synthesis. The tartaric acid-derived reagent TarB–X is capable of mediating the asymmetric reduction of aromatic ketones using either LiBH4 or NaBH4 as the reductant. Up until now, the asymmetric reduction by Tarb- H/NaBH4 had not been applied to the synthesis of chiral phthalides. Keywords: Phthalides, asymmetric reduction, sodium borohydride, TarB–H, cyclization, lactonization.