In the Ullmann condensation or Ullmann-type reaction is the copper-promoted conversion of aryl halides to aryl ethers, aryl thioethers, aryl nitriles, and aryl amines. These reactions are examples of cross-coupling reactions. Ullmann-type reactions are comparable to Buchwald–Hartwig reactions but usually require higher temperatures. Traditionally these reaction requires high-boiling polar solvents such as N-methylpyrrolidone, nitrobenzene, or dimethylformamide and high temperatures with stoichiometric amounts of copper. Aryl halide were required to be activated by electron-withdrawing groups. Traditional Ullmann style reactions used "activated" copper powder, e.g. prepared in situ by the reduction of copper sulfate by zinc metal in hot water. The methodology improved with the introduction of soluble copper catalysts supported by diamines and acetylacetonate ligands.
Ullmann ether synthesis: C-O coupling
Illustrative of the traditional Ullmann ether synthesis is the preparation of p-nitrophenyl phenyl ether from 4-chloronitrobenzene and phenol. Modern arylations use soluble copper catalysts.
Goldberg reaction: C-N coupling
A traditional Goldberg reaction is illustrated by the synthesis of fenamic acid, an intermediate in the preparation of acridone: Aryl iodides are favored arylating agents. The catalyst used is formed from copper iodide and phenanthroline. As this reaction proceeds well with an electron-rich aryl iodide it is a valuable alternative to the Buchwald–Hartwig amination reaction, which gives best yields with electron-poor aryl halides. The scope is extended to amides.
Hurtley reaction: C-C coupling
The nucleophile can also be carbon as in a carbanion as well as cyanide. In the traditional Hurtley reaction, the carbon nucleophiles were derived from malonic ester and other dicarbonyl compounds: More modern Cu-catalyzed C-C cross-couplings utilize soluble copper complexes containing phenanthroline ligands.
C–S coupling
The arylation of alkylthiolates proceeds by the intermediacy of cuprous thiolates.
Mechanism of Ullmann-type reactions
In the case of Ullmann-type reactions, the reaction involves copper alkoxide, copper amides, copper thiolates. The copper reagent can be generated in situ from the aryl halide and copper metal. Even copper sources are effective. A number of innovations have been developed with regards to copper reagents. These copper compounds subsequently react with the aryl halide in a net metathesis reaction: In the case of C-N coupling, kinetic studies implicate oxidative addition reaction followed by reductive elimination from Cuintermediates :
History
The Ullmann ether synthesis or is named after its inventor, Fritz Ullmann. The corresponding Goldberg reaction, is named after Irma Goldberg. The Hurtley reaction, which involves C-C bond formation, is similarly named after its inventor.
