Copper-mediated reactions amination

The tricyclic core of duocarmycin has been produced by a novel copper-mediated aryl amination reaction, which cleanly gives the cyclized product under exceptionally mild conditions <2003JA6630>. Selective /) tw-bromination of indoline with T-bromosuccinimide (NBS) in DMF followed by aryl amination using 2 equiv of copper iodide quantitatively provides the indolinone (Equation 71). 

B. Copper-mediated Reactions of Arylboronic Acids with Amines. 510... 

Copper-mediated reactions of arylboronic acids with aromatic and aliphatic amines... 

The above proposal is supported by the lack of reaction of electron-deficient arylamines, such as p-N02-aniline and p-Et02C-aniline, in the copper-mediated reactions with lead acetates because of the inability of the amines to reduce Cu(II) to Cu(I). This lack of reduction is indicated by the lack of a color change upon addition of Cu(OAc)2 to a solution of either of the amines. Further, the presence of Cu(III) species may be responsible for the formation of arenes and polymeric species during the A-arylation of anilines that are easily oxidized (Scheme 11). 

Denmark and co-workers reported the first example in 1990 [16], using substrates 1, synthesized from achiral allylic alcohols and readily available optically active amine auxiliaries. Substrates 1 were then employed in copper-mediated allylic substitution reactions, as shown in Scheme 8.4. 

Fig. 16.6. Copper-mediated nucleophilic substititon reactions with aryl iodides or bromides for the preparation of diaryl ethers, diaryl sulfides, diaryl amines and arylmalonic esters (A). Often, these reactions are also referred to as Ullmann reactions.

A. Ullmann and Goldberg Reactions Copper-mediated Amination and... 

Aromatic amines are found in biologically active natural products, common pharmaceuticals, dyestuffs, materials with conductive and emissive properties, and ligands for transition-metal-catalyzed reactions. For these reasons much effort has been spent for more than a century on methods to prepare aromatic amines. The synthetic methods to obtain these materials range from classical methods, such as nitration and reduction of arenes, direct displacement of the halogens in haloarenes at high temperatures, or copper-mediated chemistry, as well as modem transition-metal-catalyzed processes and improved copper-catalyzed processes. The following sections describe each of these synthetic routes to aromatic amines, including information on the scope and mechanism of most of these routes to anilines and aniline derivatives. 

In addition to aliphatic and aromatic amines, amides275 and sulfonamides285 have also been used as nitrogen nucleophiles for copper-mediated coupling with arylboronic acids, and these reactions provide protected anilines. 

In our seminal report, [Cu (TPMA)X][X] (TPMA = tris(2-pyridylmethyl)amine), X= Br and Cl) complexes were found to be very active in ATRA reactions of polyhalogenated compounds to alkenes in the presence of reducing agent (AIBN). Tetradentate nitrogen-based ligand TPMA was chosen for this study because its complexation to Cu X (X=Br or Cl) results in a formation of one of the most active catalysts in copper mediated ATRP (vide... 

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