Oxidative palladium pivalate

Imidazole /V-oxide substrates may be used in a similar fashion. Initial investigations revealed that the use of palladium acetate in conjunction with an electron deficient 4-fluorophenylphosphine in acetonitrile at 70 °C provides C2 arylation in high yields. With the goal of achieving the same reactivity at or near room temperature it was determined that the use of palladium acetate in conjunction with a Buchwald ligand, catalytic copper bromide and 30 mol% pivalic acid in acetonitrile could also achieve high yields of C2 arylation at 25 °C. As was the case with thiazole V-oxides. if the C2 and C5 positions of the imidazole are blocked C4 arylation may also be achieved in synthetically useful yield (Scheme 15). 

O/t/20-arylation of benzoic acids is often preferable to ortho-arylation of benzamides if conversion of the amide moiety to other functional groups is desired. However, only a few reports have dealt with the orf/io-functionalization of free benzoic acids due to challenges that involve such transformations. The reactions can be complicated by decarboxylation of the product and the starting material. Despite those difficulties, several methods for direct o/t/io-arylation of benzoic acids have been developed. Yu has shown that arylboronates are effective in arylation of benzoic acids under palladium catalysis [59], The reactions require the presence of palladium acetate catalyst, silver carbonate oxidant, and benzoquinone. Even more interestingly, the procedure is applicable to the arylation of unactivated sp3 C-H bonds in tertiary carboxylic acids such as pivalic acid (Scheme 13) if aryl iodide coupling partner is used. Aryl trifluoroborates can also be used [60],... 

The protocols for the utilization of ketone-derived silyl enol ethers in Tsuji-Trost reactions were preceded by a report of Morimoto and coworkers on the enantioselective allylation of sUyl ketene acetals 88. Without external activation, they reacted with the allylic substrate 19d in the presence of the palladium complex derived from the amidine ligand 89 to give y,5-unsaturated esters 90 in moderate chemical yield but high enantiomeric excess (Scheme 5.29) [46]. Presumably, the pivalate anion hberated during the oxidative addition functions as an activator of the silyl ketene acetal. The protocol is remarkable in view of the fact that asymmetric allylic alkylations of carboxylic esters are rare. Interestingly, the asymmetric induction originates from a ligand with an uncomplicated structure. The protocol seems however rather restricted with respect to the substitution pattern of allylic component and sUyl ketene acetal. 

To date, only one report has referred to the direct allqmylation of indoles under aerobic conditions. In 2010, Li and co-workers described a palladium-catalyzed oxidative coupling of 1,3-dimethylindoles with phenylacetylenes." Using a buffer system composed of 20 mol% cesium carbonate and 2 equiv. pivalic acid at 80 °C, the desired cross-coupling products were obtained in moderate-to-good yields (Scheme 9.21). 

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