Expanding the Scope of Organobismuth Compounds in Organic Synthesis

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Bismuth is the 83rd element of the Periodic Table. This heavy metal is the last stable atom of group V of the main p block elements, called the pnictogens. Despite its heavy atomic weight, elemental bismuth shows surprisingly low toxicity. In fact, bismuth-derived compounds have been used as antibiotics, radiopaque bone cements, anticancer agents, drugs for the treatment of gastrointestinal disorders and in many other medicinal applications.Organobismuth compounds, a class of organometallic reagents that contain a C-Bi bond, are subdivided into two main groups: trivalent and pentavalent organobismuthines where the metal is in the +3 and +5 oxidation state, respectively. A wide diversity of geometries have been found for organobismuth compounds depending on the oxidation state of bismuth (+3, +5), its overall charge (-1, 0, +1, +2) and its number of coordinated elements (3, 4, 5, 6). Due to its lone pair, trivalent organobismuthines can act as sigma-donor ligands in transition metal complexes. In addition, even though bismuth has a full electronic shell, organobismuth compounds can also act as Lewis acids by forming hypervalent interactions with ligands. Due to these remarkable and unique properties, organobismuth compounds have found applications in total synthesis, methodology development, polymerization reactions as well as in 'green', organometallic and medicinal chemistry.Our group reported protocols to prepare functionalized triaryl, trialkyl and tricyclopropylbismuthines. In particular, we developed an efficient strategy for the synthesis of highly functionalized triarylbismuthines that involves direct triple functional group manipulation directly on the organometallic species. These organobismuth compounds were used in a portfolio of copper-catalyzed arylation, alkylation and cyclopropylation reactions as well as in palladium-catalyzed cross-coupling reactions with aryl/heteroaryl and vinyl halides and triflates. These methods, which lead to the construction of C-C, C-N and C-O bonds, operate under mild conditions, show high functional group tolerance and allow the installation of functionalized groups on medicinally relevant scaffolds.In this research program, we propose to use the unique properties of organobismuth compounds to develop novel reactions that allow the modification of bioorganic compounds, enable new types of reactions, and give access to synthetically challenging molecules. We will also prepare novel organobismuth compounds that have unique electronic, steric and geometric properties, that possess solubilizing groups, that lead to hypervalency and chirality, and that can find applications in catalysis, electrochemistry, material sciences and tectonics. This program is ideally suited for training highly qualified personnel with multidisciplinary skills in the field of catalysis, organic, organometallic and green chemistry.