Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 33

Me Me

[Pd]
Ligand

TfO Cl (HO) 2 B

R

Ligand R Yield

95%

P( t -Bu) 3 OTf

PCy 3 Cl 87%

Figure 2.11 Ligand-controlled chemoselective Suzuki-Miyaura couplings with p-
chlorophenyltriflate.

Fu's group further expanded the scope and versatility of this and related
catalyst systems in SMC reactions. 41 Notably, they described conditions for
the room temperature coupling of aryl bromides, activated and heterocyclic
aryl chlorides and aryl triflates. Although P(t-Bu) 3 proved to be an ecient
ligand for promoting SMC reactions of aryl chlorides and bromides, the
analogous reactions utilizing aryl triflates showed diminished activity with
this ligand. They speculated that the increased steric demand of triflates
relative to bromides and chlorides may be the cause of the precipitous de-
crease in reactivity. They discovered, however, that with the use of the less
bulky PCy 3 ligand, aryl triflates could be coupled in high yield at room
temperature. Further expanding on this catalyst-controlled selectivity ob-
servation, they further elegantly demonstrated that a Pd catalyst system
based on P(t-Bu) 3 could be used to couple an aryl chloride chemoselectively
in the presence of an aryl triflate - an unexpected selectivity switch
(Figure 2.11). With the use of a catalyst system based on PCy 3 , the ''con-
ventional'' pattern of reactivity was observed (ArOTf 4ArCl).
A theoretical mechanistic investigation by Schoenebeck and Houk iden-
tified the origins of this observed ligand-controlled chemoselectivity: the
monoligated phosphine complex Pd[P(t-Bu) 3 ] was the active catalyst in the
selective oxidative addition to the aryl chloride, whereas the bis-ligated
complex Pd(PCy 3 ) 2 was implicated in the chemoselective aryl triflate re-
activity. 42 More recently, Proutiere and Schoenebeck demonstrated that Pd/
P(t-Bu) 3 can engage in chemoselective Ar-OTf activation in polar solvents. 43
A ''bis-ligated'' anionic Pd species - [PdP(t-Bu) 3 X] - in which a salt anion is
acting as a ligand - was proposed as the active catalytic species in polar
solvent on the basis of experimental and DFT studies. Fu and co-workers
have expanded their early work into several facets of cross-coupling, dem-
onstrating that Pd/P(t-Bu) 3 -based catalysts are similarly highly reactive
towards aryl chlorides in Stille, 44 Negishi 45 and Heck-Mizoroki 46 reactions.
In an early study on ketone enolate a-arylation, Hartwig's group found that
an ecient catalyst was generated using the bisphosphine ligand dtbpf (1,1 0 -
bis(di-tert-butylphosphino)ferrocene). 47,48 Although the ligand in this study
is a chelating bisphosphine (see Section 2.3.2), through 31 P NMR studies of a
transmetallation complex (dtbpf)Pd(Ar)enolate generated in a stoichiometric
reaction, it was observed that only one of the phosphines was coordinated to