Amides Buchwald-Hartwig amination, coupling

A more recent publication by Weigand and Pelka has disclosed a polymer-bound Buchwald-Hartwig amination [40], Activated, electron-deficient aryl halides were coupled with conventional PS Rink resin under microwave irradiation. Subsequent acidic cleavage afforded the desired aryl amines in moderate to good yields (Scheme 7.22). Commercially available Fmoc-protected Rink amide resin was suspended in 20% piperidine/N,N-dimethylformamide at room temperature for 30 min to achieve deprotection. After washing and drying, the resin was placed in a silylated microwave vessel and suspended in dimethoxyethane (DME)/tert-butanol... 

Despite the success of the original Hartwig-Buchwald protocol, this procedure was not without its drawbacks. The scope was limited to aryl bromide substrates and secondary amine coupling partners, and the requirement of a strong rert-butoxide or amide base meant that substrates with base-sensitive fimctional groups would not be compatible. While this latter constraint has since been obviated by the discovery that weaker bases such as CS2CO3 can promote the reaction, the extension of the scope has required some sophisticated catalyst development (vide infra). 

Arylation of a wide range of NH/OH/SH substrates by oxidative cross-coupling with boronic acids in the presence of catalytic cupric acetate and either triethyl-amine or pyridine at room temperature in air. The reaction works for amides, amines, anilines, azides, hydantoins, hydrazines, imides, imines, nitroso, pyrazi-nones, pyridones, purines, pyrimidines, sulfonamides, sulfinates, sulfoximines, ureas, alcohols, phenols, and thiols. It is also the mildest method for NIO-vinylation. The boronic acids can be replaced with siloxanes or starmanes. The mild condition of this reaction is an advantage over Buchwald-Hartwig s Pd-catalyzed cross-coupling. The Chan-Lam C-X bond cross-coupling reaction is complementary to Suzuki-Miyaura s C-C bond cross-coupling reaction. 

Clearly, the use of stoichiometric amounts of organo tin compounds is the main disadvantage of this type of C-N coupling reaction both for ecological reasons and with regard to practicability. Thus, from an industrial point of view the aim was to replace the tin amides by simpler amino sources, ideally the amines themselves. Again independently, Buchwald et al. [8] and Hartwig et al. [9] reported... 

---