Asymmetric Oxidative C-C Bond Forming Reactions

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The development of chiral catalysts for oxidative C-C bond formation has become a major focus in our laboratory.  In addition to the substantial potential for developing biomimetic synthetic approaches to a variety of natural products, such transformations are appealing in that C-H bonds are directly transformed to C-C bonds with an inexpensive oxidant, molecular oxygen.  Under these circumstances, additional activation of the coupling centers (i.e., as halides) is not necessary and the main byproduct of the reaction is water. With this motivation, we developed 1,5-diaza-cis-decalin copper catalysts which have proven to be the catalyst of choice for the oxidative asymmetric biaryl coupling of 2-naphthol derivatives.  The novel chiral diamine utilized in this catalyst was identified using database mining. The application of the oxidative biaryl coupling to the first synthesis and the first asymmetric synthesis of the natural product nigerone has recently been completed.  The synthesis of cercosporin, hypocrellin, and elsinochrome, members of the perylenequinone class of natural products, that display promising photodynamic therapy profiles in cancer treatment, is currently underway.  Future goals include exploiting the oxidative biaryl coupling method in the synthesis of chiral bisanthraquinone and naphthodianthrone natural products.