Ru(ii)-catalyzed regioselective (3 + 2)-annulation of anilines with allenes to access 2-vinylindoles

Direct access to 2-vinylindole motifs from commercially available aniline precursors is an appealing yet challenging task. Conventional strategies often rely on pre-functionalized indoles or require harsh reaction conditions and so direct annulation of simple anilines for their synthesis remains an attractive alternative. Herein, we disclose a cost-effective Ru(ii)-catalyzed regioselective (3 + 2)-annulation of N-pyridyl anilines with allenyl carbinol acetates to access 2-vinylindoles at room temperature. The reaction proceeds through an unprecedented 3,2-migratory insertion of allenyl carbinol acetates to form a Ru-alkenyl intermediate, which is elusive so far in C-H activation. Catalyst screening revealed that the regioselectivity of migratory insertion of allene is governed by the nature of the metal-salt. While Ru(ii) favors the desired 3,2-insertion, Co(iii) promotes 2,1-insertion leading to a Co-σ-allyl intermediate. The synthetic process allows access to a large library of 2-vinylindole derivatives from commercially available anilines in good to moderate yields under mild conditions. Interestingly, bis-annulation with the substrates having di-amino functionalities was also successfully carried out to access highly conjugated bisindole architectures. Additionally, the versatility of the protocol was showcased by carrying out late-stage modification of various natural products, gram-scale synthesis, and further functionalization of the products along with photophysical studies of 2-vinylindole derivatives.