Handbook of Functionalized Organometallics Applications in S

204
6 Polyfunctional Tin Organometallics for Organic Synthesis
plexity in either the organotin or the electrophilic coupling partner. Secondly,
organostannanes are accessible by numerous methods, and easy to handle since
they are relatively insensitive to moisture and oxygen.
6.2.1.1 Mechanism
In terms of mechanism, the stille coupling is characterized by a sequence of: (i)
active Pd 0 species formation, (ii) oxidative addition, (iii) transmetallation and (iv)
reductive elimination.
Detailed mechanisms will not be discussed here, but the reader can refer to
recent reviews [4]. If both the oxidative addition and the reductive elimination are
reasonably understood, the transmetallation step is still a matter of intense
debate. In any case, it is noteworthy that the nature of the ligands on the palladium
may exert a dramatic influence on the kinetics of the transmetallation step.
Moreover, the transmetallation rate was also found to depend on the nature of the
group transferred from the organotin with the generally accepted order: alkynyl>alkenyl>aryl>allyl>benzyl>>>alkyl.
There is no ideal catalytic system for a given
reaction and several factors (ligands, additives, cocatalyst, solvents) have to be
considered.
6.2.1.1.1 Ligands and Catalysts
Pd(PPh 3) 4 is a commonly used catalyst for the Stille cross-coupling reaction. However,
several studies demonstrated that the Pd/phosphine ratio exerts a dramatic
influence on the kinetics, in the fact that an excess of ligand would inhibit the
coupling by slowing the formation of the coordinatively unsaturated PdL 2 active
species. Pd(PPh 3) 4 can be replaced by the correct combination of Pd 2dba 3/phos-
O
N
O
O O
S
N
N
N
Scheme 6.1
SnMe 3
CO 2 CHPh 2
O O
S
I
+
CO 2 CHPh 2
+
I
NO 2
Me 3 Sn CONH 2
Pd 2 dba 3
THF
Pd 2 dba 3
THF
N
O
O O
S
N
CO CHPh 2 2
65%
O
N
N
O O
S
78%
CO 2 CHPh 2
CONH 2