Photocatalyzed and Enantioselective Umpolung C-C Bond Forming Reactions of Carbonyls

Project Summary
New methods for the formation of carbon-carbon bonds are always at the forefront of organic reaction
development. Of particular interest are those that utilize benign reagents, are atom-economical, and have low
energy input. The projects detailed herein will develop new umpolung carbon-carbon bond forming reactions
with visible-light mediated photocatalysis. Specifically, the projects seek to generate radical species by electron
transfer with ketone-containing functional groups. This reactivity will be enabled by photocatalytic electron
transfer either to or from an activated carbonyl species. Two specific goals will be approached: 1) Initial work will
extend preliminary experimental results that have shown that ketyl radicals can be generated by the combined
activity of photocatalysts and titanium complexes to react unactivated ketones and enones; and 2) electron
transfer from 1,3-dicarbonyls is proposed to generate electrophilic radicals for carbon-carbon bond formation
with nucleophiles. A variety of carbon-carbon bond forming reactions that involve ketyl and 1,3-dicarbonyl
radicals are proposed, including homoaldol additions, enantioselective hydroalkylation, and oxidative enolate
heterocoupling. In total, these new catalytic processes will provide highly efficient methods for the use of visible
light to construct carbon-carbon bonds in complex and biologically relevant molecular settings. The achievement
of the designed umpolung reactivity of carbonyl-containing compounds by single electron reduction or oxidation
would broaden the scope of reactivity for these widely available reagents. As a result, this proposal will contribute
to the general toolbox of carbon-carbon bond forming reactions with new methods that are able to simultaneously
build molecular complexity and adjust oxidation state. The projects are specifically tailored to be carried out by
a research team composed entirely of undergraduates and are therefore divided into discrete individual projects.
This proposal would enhance the research training and outcomes of a diverse group of undergraduates pursuing
careers in the biomedical sciences.

Grant Number: 2R15GM137238-02A1
NIH Institute/Center: NIH
Principal Investigator: Jeffrey Cannon