Meerwein Arylation

In 1939, German chemist Hans Meerwein and colleagues studied the reaction of diazo compounds with alpha, beta-unsaturated carbonyl compounds, in which the aryl group was added across the double bond and a molecule of nitrogen was lost. In one such experiment, coumarin was reacted with p-chlorodiazonium chloride in the presence of a copper(II) chloride catalyst to produce 3-(p-chlorophenyl)coumarin. Subsequently, the arylation of substituted alkenes with aryldiazonium halides in the presence of a metal catalyst became known as the Meerwein arylation.

Generally, the aryldiazonium halides are prepared through the diazotization of the aromatic amines using sodium nitrite and aqueous hydrohalic acids, and then reacted immediately with the alkenes in an organic solvent such as acetone or acetonitrile.

The Meerwein arylation reaction has been used in many successful synthesis campaigns, including in the preparation of a series of peptide mimetic aldehyde inhibitors of calpain by Ron Bihovsky, and in the first synthetic process for the synthesis of N(5)-ergolines by the research group of Jack E. Baldwin.