Palladium‐Catalyzed Amination of Aryl Halides and Sulfonates

Abstract

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or triflates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the CaN bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by NaH activation. Side products are formed by b-hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review.

Amine, Phenol, Alcohol, and Thiol Arylation

“…The Buchwald-Hartwig amine arylation has its roots in the industrial need for arylamine compounds [2,3,12]. In their 2012 review on the issue of Pd-catalyzed cross-coupling, Colacot and Snieckus considered this reaction to be part of a second wave in the development of Pd-catalyzed reactions, as the focus is on the refinement and optimization of the reaction conditions [12a].…”

“…As the deprotonation of the coordinated amine precedes the reductive elimination, the steric bulk of the ligand -which is generally a phosphane -is a critical factor [12b]. The intramolecular version of this reaction is known [2]. It must be noted that in the initial reactions, P(o-Tol) 3 was used as part of the catalyst; however, some diphosphane complexes such as 1,1 ′bis(diphenylphosphino)ferreocene (dppf) and 2,2 ′ -bis(diphenylphosphino)-1,1 ′ -binaphthyl (BINAP) showed improvements for the coupling of aryl bromides and iodides with primary alkyl amines [2].…”

“…It must be noted that in the initial reactions, P(o-Tol) 3 was used as part of the catalyst; however, some diphosphane complexes such as 1,1 ′bis(diphenylphosphino)ferreocene (dppf) and 2,2 ′ -bis(diphenylphosphino)-1,1 ′ -binaphthyl (BINAP) showed improvements for the coupling of aryl bromides and iodides with primary alkyl amines [2]. [2]. [2].…”

“…This reaction involved the 1,4-addition of aniline to an ynone, followed by an intramolecular Buchwald-Hartwig amination. The reader should also be aware that Hartwig [2] gives a lot of good examples until about 2004. In Hartwig's review [2], a number of key applications are given for this methodology (until about 1999), and a recent review of this reaction by Lundgen and Stradiotto [14d] covers this reaction until 2012.…”

“…(R)-MOP (6.6 mol%), Pd(OAc) 2 In the context of medicinal chemistry, in 2012, a team from AstraZeneca reported the synthesis of some interesting heteroaryl amines via the coupling of heteroaryl amine precursors with aryl or heteroaryl bromides (Figure 2.5) [32]. This was a considerable advance in the synthesis of these compounds.…”