| The research presented herein describes a new approach toward the total synthesis of natural products. The described method utilizes the transition metal platinum to functionalize remote C–H bonds of complex intermediates in a selective fashion. General strategies are presented centered on coordination-directed C–H bond activation, where a suitable heteroatomic function is used to direct the activated metal complex to a specific alkane region of the substrate. The proof of principle for this approach is demonstrated by the synthesis of the antimitotic alkaloid rhazinilam. A suitable heteroatomic function is used to direct an activated platinum complex to a specific alkane region of the substrate in such a way as to prevent interference of other functional groups. Extension of the methodology utilizing chiral ligands resulted in the synthesis of the enantiomerically pure isomer of this natural product. Achievement of an important goal, catalytic C–H bond functionalization, was realized utilizing α-amino acids as substrates to generate γ-hydroxy amino acids preferentially. These results establish our approach as a viable method for planning syntheses, and lay the groundwork for further exploration. |
