Ancillary Ligand Design in the Development of Palladium Catalysts for Challenging Selective Monoarylation Reactions - New Trends in Cross-Coupling: Theory and Applications - page 249

from readily available phenols and the associated increase in atom economy
in comparison with the use of higher molecular weight sulfonate leaving
groups, such as tosylates or triflates. 70 Furthermore, the derived cross-
coupling by-product formed upon workup, methanesulfonic acid, is natur-
ally occurring and undergoes biodegradation in wastewater processing. 71
Despite intense research efforts, the development of palladium catalysts for
BHA and AA chemistry that are capable of facilitating turnover of the aryl
mesylate, while circumventing phenol formation, has proven to be a con-
siderable challenge. 70 Indeed, the successful incorporation of aryl mesylates
into metal-catalyzed a-arylation was reported for the first time by Alsabeh
and Stradiotto in 2013, 72 where the [Pd(cinnamyl)Cl] 2 /L10 catalyst system
was shown to accommodate linear and cyclic dialkyl ketones, including
acetone. An optimization campaign examining the palladium-catalyzed
monoarylation of acetone with phenyl mesylate established the use of
[Pd(cinnamyl)Cl] 2 /L10 (2 mol% Pd; Pd:L10 ¼ 2:3), acetone (10 equiv.) and
K 3 PO 4 (2 equiv.) in tBuOH-1,4-dioxane (1:1; 0.125 M) at 90 1C for 16 h as
being effective conditions for the formation of phenylacetone (85% yield).
Although Cs 2 CO 3 was shown to be the optimal base in the [Pd(cinnamyl)Cl] 2 /
L10-catalyzed monoarylation of acetone using aryl halides and tosylates (see
Section 5.4.1), 68 this base, and also CsF and NaOtBu, afforded poor con-
version to the target phenylacetone. Moreover, the use of acetone as the
reaction solvent or using 1,4-dioxane or tBuOH individually at higher sub-
strate concentrations (0.5 M) resulted in high conversion of the phenyl
mesylate, but poor product selectivity. Alternative catalyst systems
featuring L1, L2, L4, L9, L11 or L13 each afforded diminished yields ( o 40%)
of phenylacetone relative to L10 under similar conditions. 72 In focusing
the discussion here on acetone monoarylation chemistry using the
[Pd(cinnamyl)Cl] 2 /L10 catalyst system (2-5 mol% Pd; Pd:L10 ¼ 2:3), under
the aforementioned optimized conditions a selection of electron-neutral and
electron-rich aryl mesylates were accommodated, with some demonstrated
tolerance for functional groups, including pyrrole, trifluoromethyl, diaryl
ether and nitrile groups (12 examples; 47-85%; Figure 5.13, B). However,
efforts to accommodate electron-poor and ortho-substituted aryl mesylates
were unsuccessful, primarily resulting in decomposition of the starting
materials to the corresponding phenol. 72
5.4.3 Palladium-Catalyzed Acetone Monoarylation Using Aryl
Imidazolylsulfonates
The application of aryl imidazolylsulfonates (ArOSO 2 Im) as electrophiles
in the monoarylation of acetone and other ketones was described by
Ackermann and Mehta in 2012. 73 As with aryl mesylates, phenol-derived aryl
imidazolylsulfonates are attractive in part due to the self-destructive and
non-genotoxic properties of the imidazolylsulfonic acid by-product formed
upon workup. Catalyst screening using Pd(OAc) 2 -ligand mixtures (5 mol%
Pd; Pd:ligand ¼ 1:2) and Cs 2 CO 3 (2 equiv.) in acetone-1,4-dioxane (1:4 by