Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 63

I

R

Pd(Q-phos) 2

I

R

X n toluene, 100 °C

78 - 97 %

n

X

via:

R

I

Pd

n

X

Figure 2.54 Carboiodination reactions promoted by Pd(Q-Phos) 2 .

N,N-Dimethyl-4-(di-tert-butylphosphino)aniline 188 (A ta -phos, also referred
to as AmPhos 189 ) 48 is an aryl dialkylmonophosphine ligand originally de-
veloped by Guram et al. at Amgen for SMC reactions of heteroaryl chlor-
ides. 190 Using Pd(AmPhos) 2 Cl 2 148 (Pd-132), a variety of heteroaryl chlorides
underwent ecient coupling with arylboronic acids with 1 mol% of catalyst
(Figure 2.55). They later expanded the scope and included the use of aryl-
boronate esters and heteroarylboronic acids. 191 The success of this ligand
versus the unsubstituted phenyl derivative highlights the importance of the
electronic properties of the ligand as PhP(t-Bu) 2 and AmPhos are isosteric.
Lipshutz and co-workers showed that Pd(AmPhos) 2 Cl 2 (Pd-132) is an excel-
lent catalyst for micellar Negishi-type couplings in or ''on'' water using the
phase-transfer surfactant polyoxyethanyl a-tocopheryl sebacate (Figure 2.56). 192
Stereospecific Suzuki-Miyaura reactions of arylboronic acids and alkyl a-
cyanohydrin triflates occur in high yield and with nearly complete inversion of
absolute configuration using Pd-132, as shown by He and Falck (Figure 2.57). 193
Additionally, Pd-132 has been used in a kilogram-scale Suzuki-Miyaura
reaction in the process route to a pyrazolopyridinone-based p38 MAP kinase
inhibitor by the Amgen process group (Figure 2.58). 194
Recently, Colacot and co-workers reported a highly ecient Heck alky-
nylation protocol using Pd-132 or the analogous Pd(0) complex Pd(AmPhos) 2
(Pd-149). Reactions of both aryl and heteroaryl bromides and chlorides were
described (Figure 2.59). 63f
Stradiotto and co-workers introduced a new type of aryldialkylmonopho-
sphine ligands which are structurally related to AmPhos. The design plan was
to find a middle ground between bisphosphine ligands which feature two
strong P-Pd interactions and biarylphosphines which feature one strong P-Pd
interaction and one weak C-Pd interaction (from the non-phosphine-con-
taining aryl ring; see above). The result was the discovery of a class of ligands
which feature a k 2 -P,N chelate; a strong P-Pd interaction and a moderate
N-Pd interaction, referred to as the DalPhos ligands 195 (Figure 2.60)
This class of ligands, containing an ortho-amino group and bulky 1-ada-
mantyl groups on the phosphine, has been used to generate highly active
catalysts that are effective in aryl amination reactions, 196

including mono-

arylation of ammonia 195,196a,c,f and carbonyl a-arylation 197

including the