50 Years of Giese Reaction - a Personal View.

50 years ago, a synthetic method was discovered, in which alkyl radical precursors, alkenes and hydrogen donors selectively yield 1:1:1-addition products in cyclic chain reactions. This paved the way for many variants of three-component syntheses, which became standard procedures for C,C-bond formation. For successful syntheses the different chain carrying radicals have to follow reactivity and selectivity rules. This requires knowledge of the substituent influence on substrate-, regio- and stereoselectivities of intermolecular radical reactions. These rules were experimentally elucidated, and the synthetic method was coined "Giese reaction". 20 years after its discovery in the chemical laboratory, biologists observed that microorganisms use the same synthetic strategy, which triggered our studies on biological cells. Although chemical rules in laboratory vessels and biological cells are the same, their different set-ups lead to very different features. Syntheses in homogeneous solution of a laboratory vessel is driven by kinetic effects. In contrast, most reactions in biological cells occur at protein/water interfaces, where thermodynamic interactions with enzymatic amino acids establish close contact between the educts. In addition, biochemical processes often start with metallo-cofactors that generate the productive radicals at the interface by long-distance electron transfer.