New Ring Formations Using Ni-Photoredox Catalysis for Organic Synthesis
Final Report Abstract
During my postdoctoral research, I elaborated several starting points for new projects in the group. A new methodology in the field of Pd-catalyzed C-H functionalization via transient directing groups was achieved. Here, we were able to show that aminomethylphosphonic acid, taurine as well as aminomethanesulfonic acid can be used as new and commercially available transient directing groups. Furthermore, it was shown that benzophenones can be functionalized despite the high energy which is needed for the formation of the imine in the first step of the catalytic cycle. First examples for the acetoxylation and hydroxylation in moderate yields were obtained. New retrosynthetic analysis contemplations of the two natural products Taichunin A and B were achieved. Key step for both products was the intramolecular two-folded cyclization reaction, yielding dimethyl (2E,12E)-7,8-dioxotetradeca-2,12-dienedioate and the subsequent one or two-folded lactonization. It was shown that under copper(I)-catalyzed borylative conditions a first cyclization could be achieved. On the basis of this first initial step, further investigations could lead to a new approach of both natural products. A retrosynthetic analysis for the synthesis of Libertellenone A was elaborated. Thereby, we envisioned that the desired tricycle could be synthesized in a one-pot reaction, given the fact that Michael-Claisen [3+3] reactions, Morita-Baylis Hillman reactions as well as Robinson annulations proceed under basic conditions. Unfortunately, main product of this approach was the hydrolyzed starting material. Screening reactions are underway in the laboratories. In collaboration with the Seyedsayamdost group, we tried to develop a new platform for synthesizing vancomycin as well as useful vancomycin analogues, with the aim of repurposing this drug. Therefore, the precursor building block N-Fmoc-L-3,5-hydroxyphenylglycine was prepared, whereby the literature known synthesis was reduced from 11 to 5 steps.
