Copper-catalyzed Ullmann condensations are key reactions for the formation of carbon-heteroatom and carbon-carbon bonds in organic synthesis. These reactions can lead to structural moieties that are prevalent in building blocks of active molecules in the life sciences and in many material precursors. An increasing number of publications have appeared concerning Ullmann-type intermolecular reactions for the coupling of aryl and vinyl halides with N, O, and C nucleophiles, and this Minireview highlights recent and major developments in this topic since 2004.

Angew. Chem. Int. Ed. 2008, 47, 3096 -3099 dependent on the nature of the ester group in the 2-alkyl acetoacetate (Scheme 2). Increasing the size of the b-keto ester, such as through the use of a CO 2 tBu group, affords high ee values (up to 89 %), whereas the less hindered CO 2 Et group gave lower ee values (up to 71 %).A second important parameter for the overall efficiency of the system is the electronic nature of the aromatic iodides. The authors tested different substituents on the aryl iodides, and they observed that electron-donating groups on the aryl group lead to high conversion and ee values (Scheme 3). However, susbstrates bearing electron-withdrawing groups either gave poor yields at the standard temperature (À45 8C, formation of homocoupling by-products) or required higher temperatures (À20 to À30 8C) to obtain satisfactory yields. This increase in temperature apparently results in a decrease in the optical purity, as expected. Finally the authors also demonstrated the importance of the ligand in the reaction, with the OH substituent on the proline ring appearing to be crucial for the success of the reaction in terms of enantioselectivity and yield. However, the influence of the ligand is not well understood.The efficiency of this novel catalytic system was attributed to a fine tuning of the different parameters discussed above. One of the key parameters proposed by the authors is the presence of an ortho substituent that could participate, through chelation of the oxygen atom (NH À C = O) with the copper center, in the stabilization of intermediates in the catalytic cycle. [4b, d] It is worth noting that the reaction developed by Ma and co-workers is one of the first metal-catalyzed asymmetric a arylations of a b-keto ester. A few examples of the asymmetric a arylation of enolates have already been described, but they were catalyzed by a system involving Pd [5a] or Ni [5b,c] precursors. Although these results are of high importance in asymmetric catalysis, the system developed by Ma and co-workers has some limitations. First, their system is so far only efficient with aryl iodides; cheaper aryl bromides afford the corresponding coupling products in poor yield (43 %) and ee values (37 % ee). Secondly, as the authors reported in a previous publication concerning the formation of a C À O bond by using a related system, [4b] the scope of the method is limited by the necessary presence of a chelating substituent at the ortho position. Despite those limitions, the study should represent a potential benchmark in the field of catalyzed asymmetric Ullmann coupling.Buchwald and co-workers [6] reported important results in regard to the chemoselectivity of Ullmann-type coupling reactions (Scheme 4). In a previous report in 2002, [7] Job and Buchwald presented several interesting pathways that allow the selective copper-catalyzed N or O arylation of b-amino alcohols with aryl iodides in the absence of any additional ligands. However, this reaction failed to couple longer amino alcohols, which seriousl...