Page 743 - Advanced Organic Chemistry Part B - Reactions & Synthesis

CO CH 3 0.3 mol % Pd(OAc) 2 Ar CO CH 3 719
2
2
ArBr + CH 2 PhCH 2 NEt 3 Br
NHCCH 3 base, NMP, 125°C NHCCH 3 SECTION 8.2
50–70%
O O Reactions Involving
Organopalladium
Ref. 143 Intermediates
Low Pd concentrations are beneficial in preventing precipitation of inactive Pd metal. 144
Small Pd clusters can be observed in phosphine-free systems, 145 and these particles
may serve as catalysts or, alternatively, as reservoirs of Pd for formation of soluble
reactive species.
The regiochemistry of the Heck reaction is determined by the competitive removal
of the -proton in the elimination step. Mixtures are usually obtained if more than
one type of -hydrogen is present. Often there is also double-bond migration that
occurs by reversible Pd-H elimination-addition sequences. For example, the reaction
of cyclopentene with bromobenzene leads to all three possible double-bond isomers. 146

0.1% Pd(OAc) 2
PhBr + PPh , NaOAc Ph + Ph + Ph
3
DMA
ratio: 7 83 10
Substituents with stronger electronic effects can influence the competition between
- and -arylation. Alkenes having EWG substituents normally result in -arylation.
However, alkenes with donor substituents give a mixture of - and -regioisomers.
The regiochemistry can be controlled to some extent by specific reaction conditions.
Bidentate phosphines such as dppp and dppf promote -arylation of alkenes with
donor substituents such as alkoxy, acetoxy, and amido. These reactions are believed
to occur through the more electrophilic form of Pd(II) generated by dissociation of the
triflate anion (cationic mechanism). 147 Electronic factors favor migration of the aryl
group to the -carbon. The combination of the bidentate ligand and triflate leaving
group increases the importance of electronic effects on the regiochemistry.
Y CH 2
OSO CF 3 2.5% Pd(OAc) 2
2
2.7% dppp α-arylation
+ CH 2 CH Y
Et N
3
Y = O(CH ) CH 3
2 3
NHCOCH 3

Substituents without strong donor or acceptor character (e.g., phenyl, succinimido)
give mixtures. The reason for the increased electronic sensitivity is thought to be the
143 C. E. Williams, J. M. C. A. Mulders, J. G. de Vries, and A. H. M. de Vries, J. Organomet. Chem., 687,
494 (2003).
144
A. H. M. de Vries, J. M. C. A. Mulders, J. H. M. Mommers, H. J. W. Hendrickx, and J. G. de Vries,
Org. Lett., 5, 3285 (2003).
145
M. T. Reetz and E. Westermann, Angew. Chem. Int. Ed. Engl., 39, 165 (2000).
146 C. G. Hartung, K. Kohler, and M. Beller, Org. Lett., 1, 709 (1999).
147
W. Cabri, I. Cardiani, A. Bedeschi, and R. Santi, J. Org. Chem., 55, 3654 (1990); W. Cabri, I. Candiani,
A. Bedeschi, and R. Santi, J. Org. Chem., 57, 3558 (1992). W. Cabri, I. Candiani, A. Bedeschi, S.
Penco, and R. Santi, J. Org. Chem., 57, 1481 (1992).