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.
Purely arylogous, mild, and diastereoselective: A novel, mild, cost‐effective, and highly diastereoselective methodology that exploits the arylogous concept is developed to introduce an electrophilic group at the unactivated γ‐position of phthalides. DFT calculations support a syn‐diastereoselective mechanism, which involves the participation of K+⊂crown cation.