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Parham Cyclization: History
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Chemistry, Organic
Contributor: Helena Kang

Parham cyclization is an intramolecular reaction in which an aryllithium or heteroaryllithium species, generated by halogen–lithium exchange on an aryl or heteroaryl halide, attacks an electrophilic group tethered to the same molecule. Rapid exchange at low temperature creates the organolithium intermediate while limiting competing proton transfer or reaction with external electrophiles; intramolecular addition then forms a fused or bridged carbocycle or heterocycle [1]. Tethered aldehydes, ketones, esters, amides, nitriles, epoxides, and related electrophilic sites can define the bond-forming terminus, with the particular functional group determining the immediate cyclic product [2]. The transformation is distinguished from aryne cyclization because the aryl halide is converted into an aryllithium nucleophile rather than eliminated to an aryne. It also differs from directed ortho-lithiation: halogen–lithium exchange establishes the reactive carbon, and productive ring closure requires a suitably positioned internal electrophile.

  • Parham cyclization
  • aryllithium
  • halogen–lithium exchange
  • intramolecular addition

Cyclization and Aryne Chemistry • Organic Chemistry • Chemistry • Physical Sciences

References

  1. William E. Parham; Charles K. Bradsher; Aromatic organolithium reagents bearing electrophilic groups. Preparation by halogen-lithium exchange. Accounts Chem. Res. 1982, 15, 300-305, 10.1021/ar00082a001.
  2. Jie Jack Li. Parham cyclization; Springer Nature: Durham, NC, United States, 2009; pp. 413-414. [CrossRef]
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