Asymmetric Organocatalytic 1,6-Conjugate Addition of Alkynyl 8-Methylenenaphthalen-2(8H)-one Formed In Situ: Synergistic Construction of Axial and Central Chirality

Organocatalytic enantioselective formal nucleophilic substitution reactions of α-(2-hydroxynaphthalen-8-yl)propargyl alcohols with 1-(1H-indol-3-yl)naphthalen-2-ols have been established for the first time. With the aid of a suitable chiral phosphoric acid, alkynyl 8-methylenenaphthalen-2(8H)-one was formed in situ from the corresponding α-(2-hydroxynaphthalen-8-yl)propargyl alcohol, followed by enantioselective 1,6-conjugate additions of 1-(1H-indol-3-yl)naphthalen-2-ols to afford a number of enantioenriched (Ra,Sc)-2,3-disubstituted indoles in 50-80% yields with 81-93% ee and (Sa,Sc)-2,3-disubstituted indoles in 18-40% yields with 79-96% ee. Notably, these nucleophilic substitution products were characterized by the presence of functional groups, including indole, naphthol, and alkynyl units, while exhibiting both axial and central chirality.