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Unprecedented Diastereoselective Arylogous Michael Addition of Unactivated Phthalides
Author(s) -
Sicignano Marina,
Schettini Rosaria,
Sica Luisa,
Pierri Giovanni,
De Riccardis Francesco,
Izzo Irene,
Maity Bholanath,
Minenkov Yury,
Cavallo Luigi,
Della Sala Giorgio
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201900168
Subject(s) - mesitylene , acetamide , chemistry , catalysis , trimethylsilyl , alkyl , michael reaction , solvent , medicinal chemistry , organic chemistry
Abstract 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.