Palladium-Catalyzed Denitrogenative 3+2 Cycloaddition of Benzotriazoles and Alkynes

摘要

Indoles have been widely utilized in pharmaceutical and material science. Therefore, it is of great importance to construct indole skeletons efficiently in organic synthesis. One of the most powerful synthetic methods of these compounds is palladium-catalyzed cyclization of 2-haloanilines with alkynes, which is recognized as Larock's indole synthesis and has been widely utilized in total synthesis of biologically active compounds containing indole skeletons (eq 1). This method, however, has some drawbacks from a viewpoint of atom efficiency; it is unavoidable to form a stoichiometric amount of halogenoic acid as byproducts, and therefore a large amount of bases to capture the halogenoic acid has to be required. We envisioned that benzotriazoles act as a synthetic equivalent of 2-haloanilines in palladium chemistry, since several kinds of benzotriazoles 1 are known to thermally isomerize to the corresponding 2-iminobenzenediazonium species A, which could oxidatively add to palladium (0) (Scheme 1). Herein, we report that palladium-catalyzed denitrogenative [3+2] cycloaddition of the benzotriazoles 1 with the alkynes 2 produced the corresponding indoles 3 in good to high yields with high atom efficiencies (eq 2).