Copper Catalysis

Arylation and Cyclopropylation Reactions

Cuivre

Copper

copper acetate

Copper acetate

Copper complex

Copper complex

Tricyclopropylbismuth

Tricyclopropylbismuth

Triarylbismuth

Triarylbismuth

copper reaction

Copper catalysis

Derek Barton reported in the 1980s the first arylation reactions involving organobismuth reagents. Most of these methods involved pentavalent bismuth reagents where the bismuth center is at the +5 oxidation state. At the same time, Dodonov in Russia greatly contributed to the field of organobismuth chemistry by reporting seminal arylation methods involving a wide range of substrates. Later on, Barton and Finet demonstrated that triarylbismuth reagents where the bismuth is at the +3 oxidation state could also act as arylating agents, particularly in the presence of metallic copper or copper(II) salts. Inspired by the major work of Barton, Finet and Dodonov, our group revisited the chemistry of organobismuth reagents to simplify the procedures and expand their use to a broader range of substrates. Therefore, in 2007, we reported the first synthesis of tricyclopropylbismuth and its use in the first N-cyclopropylation reaction of amides, indoles and other N–H containing heterocycles. Then, we developed a protocol for the regioselective N-arylation of indoles that operate directly from triarylbismuth reagents which can be easily prepared via the addition of Grignard reagents on bismuth trichloride and where the functional group can be modified directly on the organometallic species using various conditions. This protocol is complementary to Barton's method since it affords the product of N-arylation rather than the product of C3-arylation. Application of our protocol to OH-containing compounds allowed us to develop a mild procedure for the O-arylation of phenols and 1,2-aminoalcohols. Recently, we reactivated our program involving tricyclopropylbismuth and reported the first S-cyclopropylation reaction of thiophenols. Furthermore, this method represented the first example of formation of a S–C(sp3) bond using an organobismuth species.

Copper reactions with Bi.tiff

Our methods operate under simple conditions and even in some cases under air. Our protocols show great functional group compatibility and enable the formation of C(sp2)–N, C(sp3)–N, C(sp2)–O et C(sp3)–S bonds. These methods facilitate the preparation of molecules that can find application in medicinal chemistry such as amides, indoles, and phenols.

We are currently pursuing our research activities to find additional uses for our tricyclopropylbismuth reagent. We also aim to design and synthesize organobismuth species that incorporate non-transferable dummy ligands that stimulate the transfer of the aryl group while increasing the atom economy of the processes.