Pd–Phosphine Precatalysts for Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 105

OAc

OAc

OTMS

Br

OTMS

OTMS

TMSO

1mol%( t -Bu 3 P) 2 Pd

+

N N

OAc OAc F

F DIPA, MeCN, 33 °C

O O

H
N

H
N

SO 2 Me SO 2 Me

more than 40 kg scale

OH

OH

OH

OH

N

F

O

H
N

O

S

O

Scheme 3.10 (t-Bu 3 P) 2 Pd-catalyzed Heck alkynylation.

R 2

0.5 mol% [( p -Me 2 NC 6 H 4 ( t -Bu) 2 P] 2 Pd

R 1 R 2

R 1

+

Cs 2 CO 3 ,DMF,120°C

Cl

Scheme 3.11 [(p-Me 2 NC 6 H 4 (t-Bu) 2 P] 2 Pd-catalyzed Heck alkynylation.

of an aryl bromide as part of a process to prepare antihypercholesterolemic
azetidinone compounds (Scheme 3.10). 49 The coupling reaction was carried
out on a 40 kg scale.
Notably, our group developed a protocol for the use of aryl chlorides in
Heck alkynylation (copper-free Sonogashira) reactions. For this transfor-
mation, [(p-Me 2 NC 6 H 4 (t-Bu) 2 P] 2 Pd was identified as the best catalyst
(Scheme 3.11). 50
The crystal structure of [(p-Me 2 NC 6 H 4 (t-Bu) 2 P] 2 Pd (Figure 3.11) reveals that
it has similar Pd-P bond lengths as in the case of the other L 2 Pd(0) com-
plexes. However, it has the smallest P-Pd-P angle (174.71) whereas most
other molecules have shown perfectly linear (1801) structures (Table 3.1). It
was inferred that the ''bent'' L 2 Pd(0) species tends to be more active than the
linear Pd complexes containing monodentate ligands. It is also noted that
copper can actually inhibit the coupling reaction. 50
Continuing with an example from industry, Song et al. recently reported a
route to a hepatitis C virus inhibitor that involved the use of (t-Bu 3 P) 2 Pd as
precatalyst in a Heck reaction (Scheme 3.12). 54 The Heck reaction was fol-
lowed by hydrogenation of the olefin making both isomers converge to a
single product.