An Efficient Direct Asymmetric Synthesis of 3-Substituted Phthalides.

A facile, two-step, asymmetric synthesis of 3-substituted phthalides has been developed. The enantiopure amide, obtained through coupling of 2-iodobenzoic acid with (S)-1-(pyrrolidin-2-ylmethyl)- 1H-imidazole, was magnesiated using isopropylmagnesium chloride. Corresponding reactions with a range of aldehydes were carried out in situ by either direct addition or transmetallation using zinc(II) chloride. Intramolecular esterification of the adduct allowed the versatile asymmetric synthesis of phthalides in up to 88% enantiomeric excess. [ABSTRACT FROM AUTHOR]