New Ring Formations Using Ni-Photoredox Catalysis for Organic Synthesis

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In recent years, photoredox catalysis has evolved to a powerful methodology in organic synthesis. Typically, photocatalysts absorb light, convert it into chemical energy and perform selective molecule activations, which allow new synthetic transformations. Thus, photoredox catalysis offers new tools to apply in many fields of synthesis such as cycloadditions, C-H functionalizations or hydrofunctionalization. Furthermore, unusual reaction patterns are often observed with photoredox chemistry in comparison to traditional reaction manifolds. Noteworthy are the economical, environmentally friendly and mild reaction conditions that are tolerated by a broad range of functional groups. As a consequence of these benefits, numerous researchers have contributed to develop the transformations in photoredox systems further. Despite the significant advances, there are many opportunities for further investigations. Recently, Abigail Doyle at Princeton developed a promising Ni-photoredox catalytic method to directly carboxylate sp3-carbon-hydrogen bonds, a rare reaction type with great potential in organic synthesis. Thus, the aim of this research is to expand Ni-photoredox catalysis for new ring formations in organic synthesis. Since there are no examples of intramolecular C(sp3)-H acylations, the following questions should be addressed: (1) Can ring formations and ring annulations be achieved in the course of catalytic, intramolecular C(sp3)-H acylations? and (2) Could these new ring formations provide a basis for conceiving new approaches to challenging problems in target-directed synthesis? During the postdoctoral research, we will develop intramolecular C-H acylations into efficient reactions and demonstrate their ability to impact the planning of organic syntheses. We planned nine concise syntheses of target natural products such as fredericamycin, mitomycin and tremelin or further compounds that chemists have desired in the past. The synthesis strategy comprises the tactic of ring formation via C-H acylation, together with the application of known and/or commercially available starting materials, which may be used to accomplish short step syntheses of the required cyclization substrates. The proposed research will directly address the gap in the current state of dual-catalytic C-H acylations and generate powerful new strategies for synthesizing cyclic ketones and lactones, both of which are ubiquitous structural elements in nature and organic chemistry.