Dialkylbiaryl Phosphines in Pd-Catalyzed Amination: A User's Guide

Abstract

Dialkylbiaryl phosphines are a valuable class of ligand for Pd-catalyzed amination reactions and have been applied in a range of contexts. This review attempts to aid the reader in the selection of the best choice of reaction conditions and ligand of this class for the most commonly encountered and practically important substrate combinations.

Figure 1

Important structural features of dialkylbiaryl phosphine ligands.

Figure 2

Key dialkylbiaryl phosphine ligands for amination.

Figure 3

Other important dialkylbiaryl phosphine ligands for amination.

Figure 4

Comparison of bases typically used in Pd-catalyzed amination.

Figure 5

Simplistic troubleshooting guide for Pd-catalyzed amination.

Figure 6

Summary of reaction conditions used for different classes of nucleophile.

Figure 7

Summary of reaction conditions used for different classes of electrophile.

Figure 8

Summary of reaction conditions used for different classes of heteroaryl electrophile.

Scheme 1

Generalized catalytic cycle for Pd-catalyzed amination with dialkylbiaryl phosphines.

Scheme 2

Factors influencing the outcome of a Pd-catalyzed amination reaction.

Scheme 3

Water-mediated reduction of Pd(II) salts permits efficient amination of electron-deficient anilines.

Scheme 4

Synthesis of amine bound oxidative addition precatalyst.

Scheme 5

Activation of intramolecularly coordinated amine oxidative addition precatalyst.

Scheme 6

The application of precatalyst 1 allows arylation of anilines with low catalyst loading and short reaction times.

Scheme 7

Considerations for choice of Pd source for amination reactions.

Scheme 8

Use of LHMDS as base permits the cross-coupling of substrates bearing protic functional groups.

Scheme 9

Amination of aryl chlorides at or below room temperature.

Scheme 10

Efficient Pd-catalyzed amination of aryl iodides using L1 and L2 as ligands in toluene.

Scheme 11

Pd-catalyzed coupling of anilines and aryl nonaflates under microwave irradiation.

Scheme 12

Pd-catalyzed coupling of anilines and aryl mesylates employing L1 as ligand.

Scheme 13

Amidation of aryl mesylates employing L6 as ligand.

Scheme 14

Pd-catalyzed amination of 6-membered ring heteroaryl halides using L1 and L2.

Scheme 15

Amination of 5-membered ring heteroaryl halides using L1 or L2 as ligand.

Scheme 16

The selective arylation of 1° anilines can be conducted with high efficiency using L1.

Scheme 17

L1-based catalyst systems permit the selective N-arylation of aminophenols.

Scheme 18

L3-based catalysts allow the selective arylation of an aniline in the presence of a primary amide.

Scheme 19

L4 can be a useful ligand for the arylation of electron-deficient heteroarylamines.

Scheme 20

L1 provides an efficient catalyst system for the amination of 1° heteroarylamines under various reaction conditions.

Scheme 21

L2 is the best dialkylbiaryl phosphine for the arylation of 2° anilines.

Scheme 22

L2-based catalyst for the arylation of diarylamines.

Scheme 23

The use of an L9-based catalyst for the synthesis of triarylamines from anilines and aryl halides.

Scheme 24

L1 permits the coupling of 1° aliphatic amines with low catalyst loadings and short reaction times.

Scheme 25

L1 is the best ligand for the reaction of 1° aliphatic amines.

Scheme 26

L1-based catalyst systems provide excellent selectivity for the arylation of 1° amines in the presence of 2° amines.

Scheme 27

The efficient monoarylation of methylamine can be accomplished by the use of a L1-based catalyst system.

Scheme 28

L2 can be used for the arylation of cyclic 2° aliphatic amines under a variety of conditions.

Scheme 29

L2 can be used for the arylation of cyclic 2° aliphatic amines under a variety of conditions.

Scheme 30

L2 is the most effective ligand for the cross-coupling of acyclic aliphatic amines.

Scheme 31

Catalysts based on L3 or L4 can affect the arylation of dimethylamine.

Scheme 32

L6 is the best dialkylbiaryl phosphine for the arylation of 1° amides.

Scheme 33

Arylation of 2° amides, ureas, carbamates and sulfonamides is possible by using L10 as ligand.

Scheme 34

A variety of dialkylbiaryl phosphine ligands are suitable for the N-arylation of indoles.

Scheme 35

L4 is a useful ligand for the arylation of indazoles and pyrrazoles.

Scheme 36

The arylation of imidazole and benzimidazole can be brought about in some cases by using L5 as ligand.

Scheme 37

L4 is a useful ligand for the conversion of aryl bromides to anilines.

Scheme 38

L13 is a useful ligand for the conversion of aryl halides to anilines using LiHMDS as the ammonia surrogate.

Scheme 39

Benzophenone hydrazone can be effectively arylated with aryl chlorides and bromides.