Modern Heck Reactions - New Trends in Cross-Coupling: Theory and Applications - page 430

Pd(O Ac) 2 (2 mol%)
Me nicotinate, O 2
mesitylene-t-BuCOOH
110°C, 24 h

O

N
H

MeO N

H

O MeO

50%

Scheme 9.114 Low Pd loading intramolecular Fujiwara-Moritani reaction.

Pd(OA c) 2 (10 mo l%)
NicOx, O 2
t-AmylOH-AcOH, 80°C

N
Me

CO 2 Me

O

Me
65% ( ee 39%)

N

N

Nic Ox
(23)

Scheme 9.115 Enantioselective intramolecular Fujiwara-Moritani reaction and

chiral oxazoline ligand used.

The application of this approach to the development of enantioselective
oxidative Heck reactions was demonstrated. A chiral bidentate ligand, oxa-
zoline-appended nicotinate (23), was explored by Oestreich and co-workers
for the development of enantioselective cyclization. 351,352 Optical yields were
only low to modest (Scheme 9.115), which is understandable, as in the
prototypical protocol (Scheme 9.114) monodentate pyridines were used as
ligands, which probably indicates that the mechanism of these two pro-
cesses depends on monodentate-bonded stable ancillaries and thus NicOx
can also be bonded in such a mode (which can be additionally enforced by
using an acidic medium and pyridyloxazoline being monoprotonated).
Therefore, asymmetric induction from a monodentate ligand is imperfect.
Moreover, in fact, the role of ligands in oxidative Heck reactions is un-
certain. Most probably, even in the presence of ligands, the reaction can
proceed by multiple pathways, with or without chelating ancillaries in the
coordination shell; as a result, the outcome of the process is an arbitrary
sum of various processes, with individual contributions being dependent on
subtle variations of the conditions and components. Thus, unlike what
occurs in the enantioselective Mizoroki-Heck reaction, in the Fujiwara-
Moritani reaction chelating ligands cannot play a restrictive role and
decouple all ''ligandless'' pathways from the main reaction course. More
work is needed to understand the role of stable ancillaries in oxidative Heck
reactions and arriving at really enantioselective protocols, if any are even
possible. Earlier attempts 353 to design an enantioselective intermolecular
Fujiwara-Moritani reaction gave similar results.
Further application of this approach was the development of alkenylation
via intramolecular Fujiwara-Moritani reaction followed by cleavage of the
intermediate cyclic product (Scheme 9.116). 354