C-H Functionalization

C–H functionalization is often regarded as the 'holy grail' of synthetic organic chemistry. Recent advancements in organic chemistry, organometallics, and catalysis have led to significant progress in understanding the reactivity of C–H bonds and in developing robust reactions that capitalize on this knowledge. This progress suggests that the time is ripe to integrate C–H functionalization strategies into the broader retrosynthetic framework. The ability to reliably and predictably convert a C–H bond into C–C, C–N, C–O, or C–X bonds in a selective and controlled manner is beneficial, as it enhances step economy and reduces waste in chemical processes. New methods of C–H activation have expanded the range of sites that can be targeted on a molecule, providing more opportunities for its transformation into more complex structures. This approach also allows for the targeting of a variety of chemical bonds with high chemoselectivity, further enhancing the versatility of organic synthesis. When combined with traditional functional-group chemistry, C–H functionalization significantly simplifies the synthesis of complex natural products and pharmaceutical compounds. Despite its clear advantages, many organic chemistry curricula have not yet incorporated this approach, but further details are available in the C-H Functionalization Manual.