From the time we first got an inkling of the geometries and metrics of molecules, the literature of organic chemistry has contained characterizations of molecules as unstable, strained, distorted, sterically hindered, bent and battered. Such molecules are hardly seen as dull; on the contrary, they are perceived as worthwhile synthetic goals, and their synthesis, or evidence of their fleeting existence, acclaimed. What is going on here? Why this obsession with abnormal molecules? Is this molecular science sadistic at its core? Let’s approach these questions, first describing what is normal for molecules, so we can define the deviance chemists perceive. After a digression into the anthropomorphic language chemists generally use, and the psychology of creation in science, we will turn to the underlying, more serious concern: “What is the value of contemplating (or creating) deviance within science?” As many as 366,319 different eicosanes (C20H42) are conceivable, not counting optical isomers. And an enumeration of the components of a reasonably constrained universe of all compounds with up to 11 C, N, O, F atoms comes to >26 million compounds. An important feature of the chemical universe is that the tree of possible structures is denumerable. At the same time, the playground of chemical structures is subject to systematic elaboration, through the decoration of an underlying skeleton by functional groups of some stability. Very quickly a multitude turns into a universe. Of structure, and of function. Thinking of these molecules as fixed, rigid structures is natural—don’t they look like olive and toothpick assemblages, prettied up by computer rendering? And one can certainly get a long way in organic chemistry in the classical, mechanical mode. But the atoms in a molecule move continually, deviating, oscillating, as if held by springs, around an average position. The honey-comb structure of the benzene ring (a molecular tile, seemingly ever so flat and rigid as the one on your bathroom floor) has become an icon of chemistry just as the angled water molecule. Yet that tile is not rigid, it moves—and one can see the deformations/deviations by looking at its vibrational (what a telling name!) spectrum.
Rhodium-catalyzed C–H functionalization-based approach to eight-membered lactams
