The palladium-catalyzed synthesis of organic amines

Abstract

Chapter 1. The chelating ligand bis[2-(diphenylphosphino)phenyl] ether (DPEphos), in combination with palladium acetate, forms a highly active catalyst system for the coupling of anilines with aryl bromides. The bisphosphine is easily prepared in large quantity and at low cost by a known procedure. The catalyst system is effective in coupling reactions involving a variety of substrates, including electron-poor anilines or electron-rich aryl bromides. In addition, it tolerates a high degree of steric congestion at both the aniline and the aryl bromide.

Chapter 2. The synthesis of unsymmetrical N-alkyldiarylamines from a primary amine and two aryl bromides is described. A catalyst system composed of Pd(OAc)2/(rac)-BINAP is used to prepare an N-alkylarylamine (1) from a primary amine and aryl bromide. The palladium-catalyzed arylation of 1, using a different catalyst system, affords an N-alkyldiarylamine. The efficiency of each catalyst for the second step depends on the electronic nature of the substrates. This method has reasonable generality and compatibility with base-sensitive functional groups.

Chapter 3. The "one-pot" synthesis of triarylamines from an aniline and two different aryl halides is described. A catalytic system composed of Pd2(dba)3/P(t-Bu)2-o-biphenyl (1) is used to prepare a variety of triarylamines in a single flask by the coupling of an aniline with an aryl bromide and aryl chloride. The synthesis of triarylamines containing a heterocyclic aryl group is also described by employing a one flask, two-step method. These methods can be used to synthesize both discrete triarylamines and a triarylamine library.

Chapter 4. The N-arylation of indoles, including a variety of substituted ones, has been carried out using bulky, electron rich, phosphines as the supporting ligand in combination with Pd2(dba)3. Using this catalyst system, the efficient coupling of indole, pyrrole and a variety of substituted indoles with aryl iodides, bromides, chlorides and triflates can be achieved. The combination of 2-substituted indoles with aryl triflates, however, gives the C(3)-arylated product in good yields.

Chapter 5. The use of Pd2dba3 with bulky, electron-rich ligands 1 or 2 using LiN(TMS)2 as the base is described for the coupling of amines with aryl halides containing alcohol, phenol, or amide groups. This protocol expands the utility of palladium-catalyzed C-N bond formation by allowing for the use of aryl halides containing these functional groups, obviating the need for protecting group manipulations.

Chapter 6. The use of palladium chloride as a precatalyst for the amination of aryl bromides is reported. To overcome the poor solubility of palladium chloride in commonly used solvents, a procedure was developed in which PdCI2 was preheated with neat amine in the presence of a phosphine ligand before the addition of the other reaction components. This protocol is effective for a broad range of substrate combinations using several types of phosphine ligands.

Chapter 7. The in situ reduction of Pd(OAc)2 generate a useful catalyst for the coupling of anilines with aryl halides is described. In addition, these reactions proceed faster than analogous reactions using Pd2dba3. The method was also used with other amines and the extent of rate enhancements were found to be amine dependent. ...