Directed aromatic functionalization.

Victor Snieckus

doi:10.3762/bjoc.7.141

Abstract

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.

Highlights

The title of this Thematic Series brings to the minds of most organic chemists the beautifully logical aromatic electrophilic substitution (SEAr) [1,2,3,4,5] 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] (Figure 1)
Since the late 1970s, over thirty years since the independent discoveries by Gilman and Wittig, the directed ortho metalation (DoM) reaction has trickled into the armamentarium of the synthetic chemist, as a general and rational strategy for the construction of polysubstituted aromatics and heteroaromatics [15,16,17]
Once an aryl metal species was available by DoM and metal–halogen exchange or metal insertion, the gates of the syn

Summary

Introduction

The title of this Thematic Series brings to the minds of most organic chemists the beautifully logical aromatic electrophilic substitution (SEAr) [1,2,3,4,5] 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] (Figure 1).

Results

Conclusion