Aryl halides ammonia surrogate reactions

Benzophenone imine is commercially available and serves as an ammonia surrogate that reacts with aryl halides in high yields under standard palladium-catalyzed conditions. Catalysts based on both DPPF- and BINAP-ligated palladium gave essentially quantitative yields for reactions of aryl bromides. These reactions can be conducted with either Cs2C03 or NaO-/-Bu as base [137,138]. The products are readily isolated by chromatographic techniques or by crystallization. They can be cleaved to the parent aniline by using hydroxylamine, acid, or Pd/C [138]. 

So far no arylation of ammonia has been reported, and it is difficult to prepare aniline derivatives directly by the Pd-catalyzed reaction of aryl halides with ammonia. Aniline derivatives are prepared indirectly by the reaction of ammonia surrogates (ammonia equivalents). The reaction of the ammonia surrogates with aryl halides, followed by deprotection affords aniline derivatives. As one of them, LiN(TMS)2 (61) reacts with aryl bromides and chlorides. P(t-Bu)3 is the best ligand, and the coupled products are converted easily to anilines by treatment with aq. HCl. 

No smooth reaction of LiN(TMS)2 was observed with sterically congested ortho-substituted aryl halides. In such a case, Ph3SiNH2 can be used as an ammonia surrogate and the coupled product 64 was converted to 65 [52]. 

Despite the efficient utilization of benzophenone imine and metal amides as ammonia surrogates, the quest for the direct coupling of ammonia with aryl halides continued. The biggest challenge was to suppress the polyarylation of ammonia, which arises from the reaction of the corresponding anihne. Hartwig et al. [72] were the first to master this task and to report the Pd-catalyzed monoarylation of ammonia (Scheme 13.19). 

Ureas and sulfonamides have occasionally been employed as ammonia surrogates. For example, 2-(trimethylsilyl)ethanesulfonyl amide (SES-NH2) can be arylated with electron-poor or electron-neutral aiyl haUdes in the presence of CS2CO3 and a catalyst composed of Pd(OAc)2/Xantphos (Elq. 37) [227], The SES group can subsequently be cleaved with CsF, which allows other sensitive functitmal groups to remain intact. Beletskaya has reported use of urea as an NH3 equivalent in the generation of symmetrical di- and triarylamines [228, 229], The authors found that para- and /Meta-substituted aiyl halides afforded triaiylated products, whereas diarylated anilines were generated when ortho substituted aryl halides were employed (Eq. 38). These results are similar to those reported by Buchwald for iV-aiylation reactions of lithium amide [230],... 

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