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ORGANIC CHEMISTRY
Controlling the positions at which chemical groups attach to benzene rings is vital for the synthesis of materials and medicines. A reaction that targets a normally inaccessible position takes chemists closer to this goal.
In 1865, the German chemist Friedrich August Kekulé proposed that benzene has a ring-like molecular structure, allegedly after a dream containing the vivid visual metaphor of a serpent seizing its own tail1. Ever since then, aromatic molecules - those that contain benzene or benzene-like rings of atoms - have fuelled the imagination of organic chemists. From aspirin to Viagra, Kevlar to car seats, and polystyrenes to sunscreens, aromatic rings decorated with other chemical groups are now an intrinsic part of life. Yet despite the prevalence of such compounds, 'regioselective' reactions that allow groups to be placed at specific positions on benzene rings are often difficult to achieve. On page 518 of this issue, Yu and colleagues2 report a conceptually new method for attaching groups at the 'meta-position' of electron-rich benzene rings, in which a metal catalyst is guided to this difficult-to-access position.
The root of the regioselectivity problem is taught to chemistry students in their first organic chemistry course at university, in studies of classical electrophilic aromatic-substitution reactions - the most widely used reactions for attaching groups to benzene rings. To explain further, let us begin with some basic terminology. In a benzene ring, the carbon atoms on either side of the point of attachment of a chemical group are said to be in the ortho-positions; the next two around the ring are in the meta-positions; and the carbon atom on the other side of the ring from the attached group is in the para-position (Fig. 1a). If a group attached to benzene releases electrons to the aromatic ring, that group promotes the attachment of electrophilic groups (those that are attracted to electron-rich regions of molecules) at the ortho- and/or para-positions of the ring, with varying degrees...