Chapter 11:Lithium, Magnesium, and Copper: Contemporary Applications of Organometallic Chemistry in the Pharmaceutical Industry

The last two decades have been a period of tremendous growth in the field of organometallic chemistry. This chapter highlights industrial examples where problems in synthetic organic chemistry were solved using the main group metals, lithium and magnesium, and the transition metal, copper. The trend towards early incorporation of process R&D thinking into medicinal chemistry route development inspires a back to basics review of modern organometallic chemistry. This chapter is intended to inspire medicinal chemists to take another look at Li, Mg, and Cu as opposed to defaulting to use of an expensive metal. This focus is justified by the many high yielding and cost effective C–C bond forming reactions that can be accomplished using Li, Mg and Cu. Recent developments are highlighted which bring greater control with respect to reactivity, chemoselectivity, stereoselectivity, and regioselectivity. The chapter moves from the most ionic (Li) to least ionic (Cu) carbon–metal bonds with Mg bridging the middle ground. Reactions requiring a strong lithium base for C–H deprotonation, such as directed ortho-metalation (DoM), are highlighted first. Organomagnesium chemistry is highlighted second with an emphasis on applications of Knochel's TurboGrignard reagent. Organocuprate chemistry rounds out the chapter, highlighting conjugate addition and ring-opening reactions of industrial importance.