Photo-mediated generation of radical synthons from cyclopropanes

Cyclopropanes have emerged as powerful C3 building blocks in organic synthesis. Cyclopropanes serve as precursors to generate reactive intermediates in various total syntheses of natural products and bioactive molecules. Several strategies have been developed to efficiently promote C-C bond cleavage, such as Lewis acid activation and transition metal-catalyzed oxidative addition. However, these methods still face limitations, including the use of expensive transition metals, the necessity for directing groups or chelating sites, and sometimes the requirement to conduct reactions at high temperatures. With an increasing focus on sustainable chemistry, photochemistry has emerged as an effective tool to initiate radical fragmentation of the C-C bond under mild conditions. Our objective is to utilize light energy to facilitate C-C bond cleavage in cyclopropanes through energy transfer catalysis or by photoexcitation of hypervalent iodine reagents to promote oxidative activation. In this context, we first developed a photocatalyst-free method for the alkynylation of aryl cyclopropanes through the direct excitation of a hypervalent iodine reagent. We found that the reaction outcome could be completely switched from C-C to C-H alkynylation when using cyclopropyl arenes that contain two ortho substituents on the aromatic ring. In addition, the same condition was successfully applied for the 1,3-oxyalkynylation of amino cyclopropanes and 1,2-oxyalkynylation of styrene derivatives. Overall, a wide range of alkynylated products were obtained under simple reaction conditions. Subsequently, we employed a Willgerodt-type reagent to perform photo-mediated chlorination of aryl cyclopropanes, olefins and activated C-H bonds. Building on the simplicity of this reaction, we developed a one-pot protocol for substitution reactions involving benzylic chlorides with nucleophiles, resulting in the formation of C-C, C-N, C-O, and C-S bonds. Additionally, we presented preliminary results on a novel photocatalytic iodine I/III process, which opens new possibilities for future advancements in this field. We then further targeted the activation of carbonyl cyclopropanes via energy transfer catalysis. Particularly, we employed alkynes and olefins for the annulation with carbonyl cyclopropanes, giving a wide range of 5-membered carbocycles. We also utilized bicyclo[1.1.0]butane derivatives as coupling partners for the cyclization with cyclopropyl ketones, resulting in the synthesis of the bicyclo[3.1.1]heptane scaffold. We expected that the bicyclo[3.1.1]heptane products could be used as bioisosteres for 1,2,4,5 tetra-substituted arenes. Through radical trapping experiments and computational studies, we demonstrated that a 1,3-biradical was formed by the excitation of cyclopropanes, which serves as a key intermediate in this transformation. Lastly, we conducted a comprehensive study on the generation of biradical via direct excitation carbonyl cyclopropanes. This led to the d