Modern Heck Reactions - New Trends in Cross-Coupling: Theory and Applications - page 361

NH Ac

PdCl 2 (5 mol%)
AgOTf, DMF, 90°C, 1 h

Br

+

CO 2 Me

HO

NHAc

HO CO 2 Me

65%

Scheme 9.6 Isohypsic alkenylation of an electron-rich arene.

OAc

B(OH) 2 Pd(O Ac) 2 (2 mo l%)

dppp, DMF, MW 140°C, 0.5 h

64%

Scheme 9.7 Example of deborylative isohypsic alkenylation.

OAc

B(OH) 2

Pd(O Ac) 2 (2 mo l%)
dppp, DMF
continuous flow
150°C, 2 min

Cbz H N Cb zH N

63 %

Scheme 9.8 Deborylative isohypsic alkenylation in a continuous flow reactor.

This case is interesting because in spite of a close relation to the Fujiwara-
Moritani reaction, in fact it is a catalytic process without the need to re-
generate active palladium catalyst either by oxidation or by base.
Another case of the same methodology involves the reaction of aryl- and
alkenylboronic acids or aryltrifluoroborates with vinyl acetate, developed by
Larhed and co-workers, 65 which is an instance of a catalytic process that is a
complete inversion of the regular Mizoroki-Heck scheme (Scheme 9.7).
Unlike the synthesis of styrenes by arylation of ethylene or vinyl acetate,
which is plagued by diarylation, this reaction cannot lead to stilbenes, thus
being more easily controllable. Further, it is fully catalytic, not requiring any
auxiliary reagents (bases, oxidants, reductants).
The reaction was realized in a continuous flow reactor (Scheme 9.8), which
allows for a dramatic decrease in the reaction time and easy scale-up, which,
in our opinion, confirms that the mechanism is closer to that expected than
to indirect arylation of ethylene formed in situ. 66
The other potent source of diversity comes from consideration of the
initial step, the generation of s-organylpalladium species (organyl is nor-
mally aryl or alkenyl, but can also be some other types involving sp 3 , sp and
other valence states of carbon, although so far examples are few and am-
biguous). In addition to oxidative addition, transmetallation and electro-
philic palladation involved in the Mizoroki-Heck and oxidative Heck
reactions, the RPdX intermediates can be generated by other means, among
which the addition of Pd(II) species to a triple bond is a now well-recognized
family of processes. These processes are more often used in cascade