Project Summary/Abstract Carbenes are versatile reactive intermediates capable of engaging in cycloaddition, bond insertion, rearrangement, and coupling reactions. Previous efforts to develop catalytic variants of carbene transfer reactions have largely focused on the use of diazoalkanes. The primary limitation of this approach is that diazoalkanes generally must be stabilized with electron-withdrawing or aryl groups in order to avoid the spontaneous, exothermic elimination of dinitrogen gas. The overarching goal of this program is to study transition metal catalyzed reductive carbene transfer reactions that use readily available gem-dihalo reagents as precursors to non-stabilized carbenes. Catalytic turnover can be achieved using chemical reductants, such as metal powders. Alternatively, the use of photoredox or electrocatalytic reduction makes these reactions compatible with emerging flow synthesis platforms. A broad scope of catalytic cycloaddition reactions will be developed. A particular focus will be on generating odd-membered rings, which are challenging to access by conventional thermal pericyclic processes. For example, transition metal catalysis will allow current limitations of the Simmons–Smith reaction to be addressed, such as the enantioselective synthesis of dimethyl-, spiro-, and methylenecyclopropanes. Asymmetric [4 + 1]-cycloadditions of vinylidenes and 1,3-dienes will generate complex cyclopentene derivatives. Finally, three-component [n + m + 1]-cycloadditions will be developed for the synthesis of five- and seven-membered carbocycles and heterocycles. Some of these reactions will use dinuclear metal catalysts, which provide a unique active site environment to mediate carbene and vinylidene transfer reactions. Transition metal-catalyzed additions of vinylidenes to alkenes can also be diverted to non-cycloaddition pathways by intercepting metalacyclic intermediates prior to ring closure. Reaction design is based on promoting β-X elimination or transmetalation reactions of these metalacycles. Based on this concept, novel carbon–carbon coupling reactions will be developed for the synthesis of chiral alcohol and amine products. The catalysis concepts developed in this project will impact human health by providing access to complex C(sp3)-rich frameworks that can be incorporated into biological probes and therapeutics.