Syn- versus anti-carbopalladation of alkynes with organoborons: access to indoles symmetrically and unsymmetrically substituted on their 2,3-positions

A palladium (ii)-catalyzed borono-ortho-CH activation/amination cascade for the construction of two C-N bonds and one C-C bond in a single synthetic sequence is reported. This method proceeds through a formal syn-carbopalladation of alkynes with organoboron compounds, forming alkenyl palladium species, which are trapped by simple amines to provide highly substituted indoles. Remarkably, with an electron-rich arylboronic acid, the reaction proceeds through an unexpected anti-carbopalladation terminated by ortho-CH activation of diarylalkyne/amination reaction to provide an unsymmetrically substituted 2,3-diaryl indole instead. In the follow-up chemistry, we demonstrate that urea participates in this cascade to offer a variety of free NH-indoles.

Automated summary

A palladium (ii)-catalyzed borono-ortho-CH activation/amination cascade for the construction of C-N and C-C bonds in a single synthetic sequence is reported. This method involves a formal syn-carbopalladation of alkynes with organoboron compounds, followed by trapping of the resulting alkenyl palladium species with simple amines to form highly substituted indoles. In the case of electron-rich arylboronic acid, an unexpected anti-carbopalladation terminated by ortho-CH activation of diarylalkyne/amination reaction leads to the formation of unsymmetrically substituted 2,3-diaryl indole. The participation of urea in this cascade reaction is also demonstrated, providing a variety of free NH-indoles.