Pd–Phosphine Precatalysts for Modern Cross-Coupling Reactions - New Trends in Cross-Coupling: Theory and Applications - page 128

Q-PhosPd(crotyl)Cl (Pd : L ¼ 1 : 1) resulted in considerably faster reaction
rates than precatalyst (Q-Phos) 2 Pd (Pd : L ¼ 1 : 2) (Entry 3). This highlights the
importance of the precatalyst and the pathway of generation of the cataly-
tically active species, which is here presumed to be LPd(0) in all cases.
Furthermore, the effect of using allyl- versus crotyl-based precatalysts
containing the same ligand has already been discussed in Section 3.7.2. 111
3.9 Concluding Remarks
In the past 10 years, great progress has been made in terms of expanding the
substrate scope while reducing the palladium loading in cross-coupling re-
actions. This is partly due to the development of highly active, bulky, elec-
tron-rich phosphine and NHC ligand-based catalysts, although phosphines
dominate the area. A major factor in the improvement of these reactions is
the use of well-defined preformed catalysts. By using precatalysts, it is pos-
sible to avoid deleterious side reactions arising from generating the catalyst
in situ. This avoids the waste of both ligands and Pd.
Substantial research efforts have been focused on elucidating the
mechanism of each named coupling reaction by studying in detail the
rate-determining step(s). Lately, it has been noted that generation of
the catalytically active LPd(0) species is in fact crucial to the success of the
subsequent cross-coupling reaction.
By using preformed Pd catalysts, more control can be exerted over the
generation of the catalytically active species. Hence, not only is the ligand
important in a coupling reaction, but also the nature of the precatalyst
[Pd(0), Pd(I) or Pd(II)]. In addition, the ancillary ligands (e.g., p-allyl groups,
halides or other counteranions) influence the rate of activation and hence
the overall reactivity.
Although research groups have started to study the mechanism of the
formation of the catalytically active species from a number of precatalysts,
the reaction pathways are still mostly unknown. A more thorough under-
standing of the activation of preformed catalysts may lead to even more
ecient precatalysts and further reduced Pd loadings.
A list of recommended general precatalysts for selected named cross-
coupling reactions is presented in Table 3.9.
3.10 Application Table for Second-Generation
Preformed Catalysts
Although the precatalysts mentioned in Table 3.10 have been reported as
ecient in the specified coupling reactions, it should be kept in mind that
each individual cross-coupling may require a different set of conditions to
give the optimal result. This could involve using a different base or solvent
and sometimes changing the precatalyst. In short, there is no fool-proof way
of predicting which catalyst will be the best for any specific set of coupling
substrates. This table may, however, provide a good starting point in de-
veloping a user guide.