Ancillary Ligand Design in the Development of Palladium Catalysts for Challenging Selective Monoarylation Reactions - New Trends in Cross-Coupling: Theory and Applications - page 250

volume) at 80-110 1C for 16 h revealed Xantphos (L13) to be superior to a
range of other commercially available monodentate and bidentate ligands.
Reactions conducted in THF, toluene or MeCN were less successful. Inter-
estingly, whereas Stradiotto and co-workers noted that Pd(OAc) 2 afforded
vastly inferior catalytic performance relative to [Pd(cinnamyl)Cl] 2 in the
monoarylation of acetone using aryl halides and tosylates with L10 (Section
5.4.1), 68 Ackermann and Mehta noted the opposite trend when using L13 in
combination with aryl imidazolylsulfonates. 73 The optimized Pd(OAc) 2 /L13
catalyst system is attractive, given the comparatively inexpensive nature of
the catalyst components. The scope of reactivity in the aryl imidazo-
lylsulfonate was found to be very good (22 examples; 57-90%; Figure 5.13, C).
A range of at ortho, meta and para groups with electron-donating and -
withdrawing character were accommodated, including mono-, di- and tri-
substituted substrates, and also ring-fused bicyclic systems. The successful
monoarylation of acetone by use of an acetophenone imidazolylsulfonate
derivative confirms the preference of the Pd(OAc) 2 /L13 catalyst system for
acetone arylation, albeit in the presence of a significant excess of acetone.
Competition experiments established that aryl imidazolylsulfonates are
significantly more reactive than aryl tosylates or mesylates in this chemistry,
even when they are electronically deactivated. 73
5.4.4 Summary
The selective, palladium-catalyzed monoarylation of acetone has emerged as
an ecient methodology for the construction of a-aryl methyl ketones. These
newly developed cross-coupling protocols exploit acetone directly without the
requirement for stoichiometric additives or preformed enolates and have
been shown to accommodate a range aryl electrophiles, including chlorides,
bromides, iodides, tosylates, mesylates and imidazolylsulfonates. With some
notable exceptions in the case of aryl mesylates, the transformations docu-
mented thus far exhibit good functional group tolerance across several dif-
ferent catalyst systems, thereby suggesting that continued catalyst
development will lead to further practical advances (e.g., temperature, load-
ing, scope). In this vein, the first carbonylative variants of acetone mono-
arylation reactions have emerged that offer synthetic inroads to 1,3-diketone
derivatives from (hetero)aryl iodides, carbon monoxide and acetone. 74
5.5 Conclusion and Outlook
Catalyst design has contributed significantly towards advancing the state-
of-the-art in the selective palladium-catalyzed monoarylation of substrates
that are inherently prone to polyarylation, as evidenced in the context of
Buchwald-Hartwig amination and ketone a-arylation by the development of
such transformations involving ammonia, hydrazine and acetone with broad
substrate scope and excellent functional group tolerance. The judicious de-
sign/selection of supporting ancillary ligand has played a central role in