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

## TL;DR

A new method uses a ruthenium catalyst to efficiently create 2-vinylindole compounds from simple starting materials at room temperature.

## Contribution

A cost-effective and regioselective Ru(ii)-catalyzed (3 + 2)-annulation method for synthesizing 2-vinylindoles from anilines and allenes.

## Key findings

- A Ru(ii)-catalyzed reaction enables regioselective (3 + 2)-annulation of N-pyridyl anilines with allenyl carbinol acetates to form 2-vinylindoles.
- The regioselectivity of the migratory insertion is influenced by the metal-salt used, with Ru(ii) favoring 3,2-insertion over Co(iii).
- The method allows for bis-annulation and late-stage modification of natural products, enabling gram-scale synthesis and functionalization.

## Abstract

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.

Ru(ii)-catalyzed highly regioselective annulation of N-pyridyl anilines with allenyl carbinol acetates was demonstrated at room temperature for the facile access to biologically relevant 2-vinylindole derivatives.