Aryllithiums and hetaryllithiums are of great utility to the chemical community. Not only do they serve as intermediates in the synthesis of various pharmaceuticals, but they also can be used in routes to polymers, inorganic complexes, natural products, and materials. Their versatility is well known.
In the late 1930s, simultaneous research discoveries of Georg Wittig and Henry Gilman began to appear. Eventually, these two pioneers delineated some of the parameters of both the ortho‐lithiation and halogen/lithium exchange reactions. Amplification of aspects of the ortho‐lithiation reaction over the next 25 years was provided by J. D. Roberts and C. R. Hauser with articulation of the “Complex‐Induced Proximity Effect” by Roberts and the directing groups –CH
2
NMe
2
and –CONHR by Hauser. Another 10 years passed before significant addition to the capabilities of the X/Li (X = halogen, halide) exchange took place. This is attributed to W. Parham and is known as the Parham cyclization. In many respects, this advancement in the overall usefulness of the halogen/lithium exchange has become a most important component of the incorporation of the exchange into synthetic procedures.
As details of the equilibria of alkyllithium reagents in various ether and hydrocarbon solvents began to emerge, advances in mechanistic understanding of both ortho‐lithiation and the exchange were made. These advances have made the production of aryllithiums and hetaryllithiums of significant value to the synthetic chemist. Recent discoveries promise to provide safer, more efficient process conditions, thereby making both protocols more attractive for scaled processes.
With all these advances, understanding of both reactions remains incomplete. Future research promises even greater control and fine‐tuning of the variables in each reaction such that they become of even greater utility. Although other main group metal and transition metal ortho‐metalations are known, the specificity and overall economy of aryllithium and hetaryllithium generation should bring about even greater involvement of these intermediates in future research and scaled production.
