Unprecedented Diastereoselective Arylogous Michael Addition of Unactivated Phthalides

by Marina Sicignano, Rosaria Schettini, Luisa Sica, Giovanni Pierri, et.al.
Year: 2019 DOI: https://doi.org/10.1002/chem.201900168

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Chemistry European Journal.


The first highly enantioselective arylogous Michael reaction (AMR) of 3-unsubstituted phthalides has been described. This phase-transfer methodology, which uses catalytic amounts of KOH/18-crown-6 catalyst in mesitylene in the presence of N,O-bis(trimethylsilyl)acetamide (BSA), gives access to a broad range of 3-monosubstituted phthalides with high levels of syn diastereoselectivity and good yields, starting from 3-unsubstituted derivatives and diverse α,β-unsaturated carbonyl compounds. The reaction also applies to unactivated 3-alkyl phthalides to afford 3,3-dialkyl derivatives. A plausible mechanism has been suggested. DFT analysis of possible transition states gives a rationale of the high syn diastereoselectivity observed and its correlation with the solvent's dielectric constant.