Prominent Ligand Types in Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 38

O

Pd(OAc) 2 (1 mol %)
Ligand (1 mol %)

Br N

O

HN

50 °C, 1 hour

MeO MeO

Ligand Conversion

P( t -Bu) 3 36 %

DTBNpP >99 %

TBDNpP 87 %

TNpP 0 %

Figure 2.18 Comparison of P(t-Bu) 3 and neopentylphosphines in the amination of
4-bromoanisole.

The forcing conditions required to convert aryl chlorides were attributed to
the decreased electron donation of neopentylphosphines relative to P(t-Bu) 3 .
With aryl bromides, oxidative addition is more facile and the increased steric
demand gives rise to a highly active catalyst under mild conditions. Owing to
the high activity observed with DTBNpP relative to TBDNpP and TNpP and
previously reported data on Buchwald-Hartwig aminations using less steri-
cally demanding ligands (i.e., PCy 3 ) with cone angles o 1901, Shaughnessy
and co-workers concluded that the optimal cone angle for the reactions
under the conditions studied existed between 190 and 2001. Shaughnessy
and co-workers also described Pd/DTBNpP to be highly active in Suzuki-
Miyaura, Sonogashira-Heck and Heck-Mizoroki reactions of aryl
bromides and chlorides. 70 They further showed that Pd complexes of
DTBNpP are highly active in Buchwald-Hartwig aminations and arylation of
propiophenone enolate. 71 Subsequent work by Colacot's group revealed that
the preformed (p-allyl)Pd(DTBNpP)Cl is more ecient than the in situ sys-
tem. 72 The details of the study are discussed in Chapter 3. Recently,
Shaughnessy and co-workers reported that TNpP is a useful ligand in
Buchwald-Hartwig amination reactions of substrates with high steric
demand and also in Suzuki-Miyaura coupling reactions with moderately
hindered reaction partners (Figure 2.19). 73 It was proposed the conforma-
tional flexibility of this ligand is crucial to its ability to accommodate
hindered substrates.

2.3.2 Chelating Bisphosphine Ligands
As mentioned earlier, the beneficial effects of the chelating bisphosphine
ligand dppf [1,1 0 -bis(diphenylphosphino)ferrocene] was originally observed
by Kumada's group in 1979 while studying the cross-coupling of aryl
bromides with b-branched alkyl Grignard reagents. 7

The more facile