Directed aromatic functionalization

The title of this Thematic Series brings to the minds of most organic chemists the beautifully logical aromatic electrophilic substitution (SEAr) [1–5] and, to a lesser extent, nucleophilic aromatic substitution (SNAr) [2,6–7] reactions as taught to many generations of students in their first organic chemistry courses [8] (Fig. 1). Being less steeped in history, radical nucleophilic substitution (SRN1) [9] and vicarious nucleophilic substitution (VNS) [10–12], in spite of their considerable synthetic utility, are given sparse mention. By the time students reach the upper years of study, aromatic chemistry receives the label “classical” and is disregarded or relegated to brief coverage. Apart from in English schools [13], heteroaromatic chemistry suffers the same fate. As a consequence, a fresh graduate entering the pharmaceutical industry, who invariably faces a complex aromatic or heteroaromatic as his or her first target molecule, is either lost or must grope around with insufficient background knowledge.