Synthesis Review / Short Review Transition Metal-Catalyzed Directed C(sp3)–H Functionalization of Saturated Heterocycles Daniele Antermitea James A. Bull*a a Department of Chemistry, Imperial College London, White City, Wood Lane, London, W12 0BZ, United Kingdom
[email protected] Click here to insert a dedication. Received: biological interactions or selectivity profiles. The ready Accepted: Published online: availability of simple saturated heterocycle derivatives, DOI: including enantioenriched derivatives, makes them ideal Abstract Synthetic methods that can readily access saturated heterocycles starting points for further reactions. Therefore, approaches to with different substitution patterns and with control of stereo- and functionalize existing C–H bonds of these readily available regiochemistry are of huge potential value in the development of new medicinal compounds. Directed C–H functionalization of simple and building blocks appears to be of considerable potential. commercially available precursors offers the potential to prepare diverse Over the last 20 years, the concept of transition metal- collections of such valuable compounds that can probe the different available exit vectors from a ring system. Nonetheless, the presence of the catalyzed C–H functionalization has emerged with enormous Lewis basic heteroatoms makes this a significant challenge. This review potential to streamline the synthesis of complex molecules.5 covers recent advances in the catalytic C–H functionalization of saturated Specifically, transition metal catalysts can activate C–H bonds heterocycles, with a view to different heterocycles (N, O, S), substitution to form discrete C–M bonds, via different mechanistic patterns and transformations. 1. Introduction pathways.6 The resulting organometallic intermediate can then 2 a-C–H Functionalization with directing group on nitrogen form new C–C or C–heteroatom bonds with various coupling 3 C–H Functionalization at unactivated C(3), C(4) and C(5) positions partners.