A decade of bioorthogonal chemistry.

Inventing new chemical reactions is a long-standing passion of chemists, as reflected in the ever-popular field of reaction methodology. Historically, the environment in which newly crafted transformations would be performed imposed minimal limitations on reaction design; after all, solvents can be screened to find an optimal choice, temperature can be modulated, air and moisture can be excluded, catalysts can be added, competing functional groups can be protected, and byproducts can be siphoned away. Such flexibility permitted the use of diverse reagents and conditions, culminating in a vast compendium of synthetic transformations that has been wielded to produce myriad complex chemical structures. The target-driven synthetic chemist now enjoys an impressive reaction toolkit. But what if the challenge were inverted, wherein the target structure was relatively simple but the environment in which the necessary reactions must proceed was so chemically complex and uncontrollable that no two functional groups could combine reliably and selectively under such conditions?