Access to Tetrahydrothiopyrano[2,3‐b]Indole Derivatives via Zinc‐Catalyzed Asymmetric [3+3] Annulation of Indoline‐2‐Thiones with Yne–Enones

Abstract

We report herein an enantioselective [3 + 3] annulation of indoline‐2‐thiones with yne−enones by chiral dinuclear zinc catalysts via a Brønsted base and Lewis acid cooperative activation. This transformation proceeded through sequential conjugate addition, allenyl ketone formation and intramolecular sulfa‐Michael 6‐endo‐trig cyclization. A range of enantioenriched tetrahydrothiopyrano[2,3‐b]indole derivatives bearing an exocyclic double bond were obtained in moderate yields with excellent stereoselectivities (up to 20 : 1 dr, 20:1 Z/E ratio and 95% ee). Late‐stage functionalization, large‐scale experiment and further derivatizations were also explored.

Update on thiopyran-fused heterocycle synthesis (2013–2024)

“…The addition of methyl-3-hydroxy-2,2-dimethyl propanoate 98 improved the enantioselectivity of the reaction (Scheme 16). 34 This transformation proceeded through sequential conjugate addition, allenyl ketone formation and intramolecular sulfa-Michael 6- endo-trig cyclization. Tetrahydrothiopyrano[2,3- b ]indole derivatives bearing an exocyclic double bond 96 were obtained as products in moderate yields and excellent diastereoselectivities (up to 20 : 1 dr).…”