Buchwald-Hartwig amidation

Bonnaterre F, Bois-Choussy M, Zhu JP (2006) Rapid access to oxindoles by the combined use of an Ugi four-component reaction and a microwave-assisted intramolecular Buchwald-Hartwig amidation reaction. Org Lett 8 4351-4354... 

Key step was a copper-catalyzed domino Buchwald-Hartwig amidation/ Diels-Alder reaction of amide 247 with 2-bromofuran 248 to give 249. In the first... 

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... 

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. 

Heterocycles related to indoles can also be prepared using the Buchwald-Hartwig amination strategy. For instance, indazole 15 can be prepared from hydrazine 14. Benzimidazole derivatives may also be prepared from the intramolecular guanidinylation of aryl bromides. And oxindoles can be prepared from the intramolecular amidation of aryl bromides. ... 

Phosphonium-based IL-coated lipase (ILl-PS)-catalyzed reaction has been reported. ILl-PS was used as a catalyst in 2-methoxyethoxymethyl-(tri-n-butyl)-phosphonium bis(trifluoromethanesulfonyl)-amide for the transesterification of secondary alcohols [128]. McNulty et al. studied the anionic effect of Pd-catalyzed Buchwald-Hartwig amination reaction in phosphonium-based ILs [129]. Phosphonium-based ILs are also used in ... 

Formation of C-N bond has raised of interest in the scientific community in the last 10 years. In this context, the formation of enamides is a valuable protocol. In addition to conventional approaches that include condensation of amides and aldehydes, addition of amides to alkynes, acylation of imines, Curtius rearrangement of a,jS-unsaturated acyl azides, amide Peterson olefination, and Wittig and Horner-Wadsworth-Emmons reactions, several transition metal-catalyzed methods have been developed that allow the synthesis of enamides.Inspired by the analogous arylation of amines catalyzed by palladium or copper complexes (Buchwald-Hartwig reaction), a new approach for the synthesis of enamides has been published recently, which allows to prepare enamides from readily available starting materials (amides and vinyl halides) proceeding under very mild conditions. Thus, we decided to test the Porco-Buchwald amidation of vinyl halides in our synthesis [144-146]. 

One of the syntheses of 198 is based on pyrazine 200 (Scheme 47) [165, 166]. Compound 200 was transformed to methoxy derivative 201 via diazotization step 201 was then subjected to Buchwald - Hartwig amination to give 202. Ester 202 was transformed to amide 203 diazotization of 203 in the presence of pyridine hydrofluoride led to the formation of fluoro derivative 204. The last step of the synthesis included deprotection of the methyl ether to give 198. 

In 1995, Hartwig and Buchwald published concurrently their two groups results on tin-free amination of aryl halides [79,80], Instead of isolating or generating a tin amide in situ, the amination reactions were conducted by reacting an aryl halide with the combination of an amine and either an alkoxide or silylamide base (Eq. (5)). These reactions were typically conducted between 80 and 100 °C in toluene solvent. The catalysts used initially were 1, 3, or a combination of [Pd2(dba)3] (Sa) (dba = trans, trans-dibenzylidene acetone) and P(o-C6H4Me)3. Catalysts used subsequently will be described below. As shown in Table 7.1, secondary amines were viable substrates, but primary amines gave substantial yields with... 

In 1995, Hartwig and Buchwald published concurrently their respective groups results on tin-free amination of aryl halides [98, 99]. Instead of isolating or generating a tin amide in situ, the amination reactions were conducted by allowing an aryl halide to react with a combination of an amine and either an alkoxide or silylamide base (Eq. (5)). 

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. 

A tantalizing observation made by Kosugi was that triphenylphosphine-based catalysts were far inferior to PdCl2(o-tolyl3P)2 for the coupling of aryl halides with tin amides. In 1994, the groups of Buchwald and Hartwig... 

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