金属卡宾,乃春插入nature.pdf

Vol 451j24 January 2008jdoi:10.1038/nature06485 REVIEWS Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion Huw M. L. Davies1 James R. Manning1 Novel reactions that can selectively functionalize carbon–hydrogen bonds are of intense interest to the chemical community because they offer new strategic approaches for synthesis. A very promising ‘carbon–hydrogen functionalization’ method involves the insertion of metal carbenes and nitrenes into C–H bonds. This area has experienced considerable growth in the past decade, particularly in the area of enantioselective intermolecular reactions. Here we discuss several facets of these kinds of C–H functionalization reactions and provide a perspective on how this methodology has affected the synthesis of complex natural products and potential pharmaceutical agents. n 2006, 31 new chemical entities were introduced to the world strategies, whereby a highly reactive metal complex inserts into a pharmaceutical market and 2,075 molecules were in phase I or C–H bond, activating the system for subsequent transformations7–9. II of clinical development1. The majority of these were small- One of the major challenges associated with this chemistry has been I 10. A partial solution to molecule (relative molecular mass ,1,000) organic com- to render it catalytic in the metal complex pounds2. As knowledge about the specific interactions of drugs this problem has been to use neighbouring functionality to direct less in vivo increases, often so does the structural complexity of new drug reactive metal complexes to the site for functio