Intermolecular arylations, Buchwald-Hartwig

Needless to say, the Buchwald-Hartwig reaction can also be usefully employed in ways other than the efficient preparation of diphenylamines. Given the respective substitution, it should be possible to bring about the phenazine skeleton by Pd-catalyzed ring formation as well. There are two ways to proceed either the substituent pattern required by the intramolecular Buchwald-Hartwig reaction is elaborated after the formation of the diphenylamine (121 124), or the starting material already contains the substituents necessary for the two JV-arylations. A reasonable starting point is the intermolecular JV-arylation of an o-haloaniline... 

To overcome the ring closure of intermediate 10 giving rise to by-product 8 that was particularly encountered with secondary alkyl halides. Tautens and coworkers [22] developed conditions that favor the oxidative addition of alkyl hahdes. The methodology was widely applied to the intramolecular (Scheme 19.12) and intermolecular ortho alkylation of aromatic C-H bonds with secondary alkyl iodides and bromides [23]. Depending on the terminating reactions employed (the Heck reaction, direct arylation of heterocycles, and the Buchwald-Hartwig amination), a variety of valuable heterocydes were efficiently prepared. It should be pointed out that the reaction of enantioenriched substrates occurred with... 

After the intermolecular palladium-catalyzed arylation of enolates had been discovered by the research groups of Buchwald, Hartwig, and Miura [63], it was an obvious idea to explore a stereoselective variant that was based on the reliable Evans auxiliaries, while catalytic, enantioselective protocols (cf. Section 5.2) were developed at the same time. However, only relatively moderate diastereoselectivity in the formation of arylation products 133 was achieved when the silyl ketenimine (S)-132 derived from Af-propionyl oxazolidinone was coupled with aryl bromides under palladium catalysis, as disclosed by Hartwig and Liu [64]. The additive zinc(ll) f-butoxide permitted to lower the temperature to 25 °C so that the diastereoselectivity could be enhanced (Scheme 4.26). The authors noticed that Ley s chiral dioxanone 134 proves itself as an auxiliary that induced excellent diastereoselectivity and led to the formation of arylated compounds 135 in very high diastereomeric ratios. The chiral auxiliary group was readily removed by treatment with chlorotrimethylsUane and methanol, so... 

Prior to the recent paper by Buchwald, an intermolecular version of the arylation of carbamates was published by Hartwig et al. (Eq. (22)) [163]. His group showed that reactions catalyzed by a combination of Pd(OAc)2 and P(tBu)3 formed N-aryl carbamates from aryl bromides or chlorides and tert-butyl carbamate, but that this system was inactive for reactions of amides or sulfonamides. Again, the reaction conditions were not as mild as those used for animation, but they were similar to those employed in the reactions with Xantphos. For the intermolecular reactions, the use of sodium phenoxide as base was crucial. 

Recently, the limitations for the intermolecular coupling have been significantly mitigated. Kawatsura and Hartwig [14] and Buchwald et al. [15] have demonstrated that aryl bromides and even aryl chlorides react with malonates (Eq. 3) and 1,3-diketones (Eq. 4) by using sterically bulky and electron-rich phosphines, such as P(f-Bu)3, D BPF, and 2-(di-ferf-butylphosphino)-2 -methyl-biphenyl, as ligands. 

The direct intermolecular a-arylation of relatively less acidic ketones with aryl halides, which proceeds by mechanism B, was reported concurrently in 1997 by the groups of Miura, Buchwald, and Hartwig [35-37]. The intramolecular version was also described by Muratake and coworkers in the same year [38,39], while some intermolecular vinylation reaction had been reported [40, 41]. Taking advantage of this, the reaction of carbonyl compounds and related substrates has been studied extensively. Now a variety of ketones are known to be arylated by using appropriate ligands and bases [42-46]. The reaction usually takes place at a less hindered a position (Eqs. 5-7) [19,20]. 

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