Buchwald—Hartwig arylations

The powerful Buchwald-Hartwig aryl amination methodology [135-141] has been applied by Hartwig to the synthesis of N-arylpyrroles (196) [142,143]. 

Buchwald parlayed the powerful Buchwald-Hartwig aryl amination technology [439-447] into a simple and versatile indoline synthesis [448-452], For example, indole 368, which has been employed in total syntheses of the marine alkaloids makaluvamine C and damirones A and B, was readily forged via the Pd-mediated cyclization shown below [448], This intramolecular amination is applicable to the synthesis of -substituted optically active indolines [450], and o-bromobenzylic bromides can be utilized in this methodology, as illustrated for the preparation of 369 [451]. Furthermore, this Pd-catalyzed amination reaction has been applied to the synthesis of arylhydrazones, which are substrates for the Fischer indole synthesis [453,454],... 

The Buchwald-Hartwig aryl animation methodology cited above in this section was engaged by Hartwig and others to synthesize AT-arylindoles 377 [469]. Carbazole can be N-arylated under these same conditions with p-cyanobromobenzene (97% yield). Aryl chlorides also function in this reaction. The power of this animation method is seen by the facile synthesis of tris-carbazole 378 [469c]. 

The Buchwald-Hartwig aryl amination methodology cited above in this section was... 

Several tandem reaction sequences have been developed for indole synthesis featuring a Buchwald-Hartwig aryl amination as one component. For instance, a tandem double JV-arylation of substrate 5 leads to indoles 6 through a cascade of C-N bond forming reactions. A range of structurally and electronically diverse amines can be used successfully in this transformation. 

Scheme 2.2 The proposed mechanism for the Buchwald-Hartwig arylation procedure [12e, 14b, 15].

Figure 2.4 A cross-section of results for the Buchwald-Hartwig arylation of ammonia with arylchlo-rides developed by Stradlotto and coworkers [28a, b],...

The first application of the single-step procedure to the synthesis of azacafix-arenes was laimched by Ito et al., who prepared a series of azacafix[ ]arenes 4a-f with different ring sizes (w = 3 to 8) [16,17]. As shown in Scheme 2, starting from the N-methylation of 3-bromoaniline (2) in 3 steps, the resultant 3-bromo-N-methylaniline (3) was subjected to the Buchwald-Hartwig aryl amination reaction to yield azacaUxarenes 4a-f, which were isolated by medium-pressure liquid chromatography. 

Scheme 1 Catalytic cyde of Buchwald-Hartwig aryl amination reaction of aromatic halide with N-alkylanUine [12]...

Another application of the single-step procedure tvas made by Miyazaki et al, who utilized the Buchwald-Hartwig aryl amination reaction for the preparation of azacalix[6]pyridine 7d [18], in which all the benzene rings of the above azacalix[6]arene 4d were replaced by pyridine rings (Scheme 3). Azacalix[ ]pyridines 8a-f (n = 3-8) with tolyl groups on the nitrogen bridges... 

Scheme 9 8-Elimination reaction as a side reaction in the Buchwald-Hartwig aryl amina-tion reaction [12]...

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