Modern Heck Reactions - New Trends in Cross-Coupling: Theory and Applications - page 382

Cl

Br

CO 2 Me

Pd(dba ) 2, Pd(t-Bu 3 P) 2 (5 mol% Pd )
Cy 2 NMe, dioxane, r.t., 16 h

+

NHCbz

H 2 N

Cl

CO 2 Me

NHCbz

H 2 N

93%

Scheme 9.34 Room-temperature arylation of an amidoacrylate by an electron-rich
aryl bromide using the Littke-Fu method.

Cl -

PdL 2 PdL LPdCl

L

R Y

RCl

RCl

RY

RPdL

Y = sulfonates,
phosphates, etc.

L L

R Pd Cl R Pd Cl

L

Y -

L

Z

L

R Pd Cl catalytic cycle

Z

Scheme 9.35 Ligand-accelerated catalytic cycle initiation in the case of a halide
substrate (usual neutral pathway, RCl shown for uniformity) versus a
substrate with a highly nucleofugic leaving group.

co-workers discovered that with a small but very essential modification, the
Littke-Fu protocol can be applied to alkenyl tosylates and phosphonates.
The original Littke-Fu method was applied to halide substrates and is be-
lieved to follow the neutral pathway. With tosylates and similar substrates
bearing highly nucleofugic leaving groups, a switch-over to the polar path-
way would seem to be inevitable, but such a pathway is probably ener-
getically disfavoured. The addition of a soluble chloride salt is likely to lead
to a switch-back to the neutral pathway, most likely via prebinding of
chloride and formation of an anionic complex, as the alternative, post-
binding after oxidative addition, is less probable, as it does not explain the
facilitation of the process in the presence of chloride. In any case, a polar
solvent is required for ionic ligand binding to take place (Scheme 9.35).
With bulky alkenyltosylates (phosphonates), another intriguing feature
was disclosed, namely rearrangement of the alkenyl residue taking place via
a very rare PdH elimination from sp 2 centres (unambiguously proven by
experiments with deuterated substrates). In this case, the direct carbo-
palladation of the initially formed alkenylpalladium complex is probably
sterically retarded to make possible the establishment of an elimination-
addition equilibrium to bring into play the other channel with rearranged