Catalytic Enantioselective Nucleophilic Addition to Arynes by a New Quaternary Guanidinium Salt-Based Phase-Transfer Catalyst

Owing to the mild generation methods, arynes have been widely used in synthetic chemistry. However, achieving asymmetric organocatalytic reactions with arynes remains a formidable and infrequent challenge, primarily because these neutral and transient species tend to spontaneously quench. To address this issue, a solid-liquid phase-transfer strategy is devised in which the generation speed of arynes could be controlled by the in situ generated fluoride-based chiral phase-transfer catalyst. In this study, we present a catalytic enantioselective nucleophilic addition reaction involving arynes, utilizing an amino amide-based guanidinium salt QGcenter dot X. Furthermore, we demonstrate the broad compatibility of this reaction with various arynes and cyclic/acyclic beta-keto amides, leading to the creation of diverse alpha-aryl quaternary stereocenters with good stereoselectivity. Mechanistic investigations have uncovered the potential involvement of a chiral intramolecular cationic-anionic pair and HF during the ion exchange between QGcenter dot X and CsF for nucleophile activation and aryne generation. Additionally, DFT calculations suggested that the observed high levels of enantioselectivity can be attributed to steric repulsion and the cumulative noncovalent interactions between the catalysts and substrates.

Automated summary

A solid-liquid phase-transfer strategy was devised to control the generation speed of arynes, enabling a catalytic enantioselective nucleophilic addition reaction with good stereoselectivity.