Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 31

Table 2.6 Pocket angles (Y).
Entry Ligand Y (1)
1 dppe 132
2 dppp 108
3 dppb 93
4 dmpe 141
5 dcpe 106
Abbreviations: dmpe ¼ 1,2-bis(dimethylphosphino)ethane; dcpe ¼ 1,2-
bis(dicyclohexylphosphino)ethane.
Adapted with permission from Y. Koide, S. G. Bott and A. R. Barron,
Organometallics, 1996, 15, 2213. Copyright 1996 American Chemical
Society.
the details of the various types of ligands developed and utilized in various
cross-coupling reactions.
2.3.1 Bulky Trialkylphosphines - The Origins of Modern
Ligands for Cross-Coupling
Until the 1990s, studies on cross-coupling reactions were almost exclusively
focused on the coupling of aryl iodides, aryl bromides or aryl triflates, des-
pite the fact that aryl chlorides are often more attractive substrates owing to
their lower cost and wider availability. Aryl chlorides, however, had been
particularly problematic for existing catalyst systems, owing to the strong C-
halogen bond (BDE 33 ¼ 95 kcal mol 1 ) relative to those of aryl bromides
(BDE ¼ 80 kcal mol 1 ) and aryl iodides (BDE ¼ 65 kcal mol 1 ). 34 For this
reason, their use in cross-coupling reactions had been largely unexplored
with the exception of a few activated aryl and heteroaryl systems. 35 In 1989,
the groups of Osborn 36 and Milstein 37 independently reported Pd-catalyzed
carbonylation reactions of chlorobenzenes. Key to the success of these
transformations was the use of either a Pd(PCy 3 ) 2 Cl 2 36 (Cy ¼ cyclohexyl) or a
Pd(OAc) 2 /dippb 37 [dippb ¼ bis(diisopropylphosphino)butane] system. Both
groups attributed this new reactivity to the electron richness and steric de-
mand of these ligand systems. Osborn noted that ''significant catalytic ac-
tivity is found only with phosphines which are both strongly basic (pK a 46.5)
and with well-defined steric volume, that is, the cone angle must exceed
1601.'' 36 These findings began to shed light upon the importance of ligand
properties, which set the stage for further research in this area, ultimately
leading to the constant development of more active catalysts in the area of
cross-coupling.
Koie and co-workers recognized the potential of bulky trialkylphosphines
as supporting ligands in Buchwald-Hartwig amination reactions and
reported that a Pd/P(t-Bu) 3 catalyst system was highly effective in the N-
arylation of piperazine with primarily aryl and heteroaryl bromides 38 and in
the formation of triarylamines from aryl halides and diarylamines
(Figure 2.9). 39 Noted in both studies was the reduced eciency when similar