Buchwald palladium -catalyzed synthesis

The ingenious undemanding Hartwig-Buchwald palladium-catalyzed carbon-nitrogen coupling can also be favorably used for the synthesis of benzotriazoles (332). This way, both the amine and the arylhalide can be immobilized. Crucial for the success is the careful choice of the ligand used (Scheme 47). 

Finally, Buchwald and co-workers developed a high-yield, general method for the palladium-catalyzed formation of 1,4-benzodioxane. Bulky, electron-rich o-biphenylphosphines of type 214 together with Pd(OAc)2 have proved to be the most general catalytic system to avoid the /3-hydride elimination side reaction <2000JA12907>. This strategy was extended to the synthesis of enantiomerically pure 2-substituted-l,4-benzodioxanes 213 from 212 (Equation 37) <2001JA12202>. 

Most recently, Wagaw, Yang, and Buchwald published a full account of the synthesis of indoles using the palladium-catalyzed amination process [185]. From the standpoint of catalysis, new results included improved turnover numbers and rates when Xantphos was used as ligand. Moreover, this ligand allowed diarylation of the hydrazone, including a one-pot sequential diarylation to provide mixed diaryl hydrazones. A procedure for the alkylation of N-aryl hydrazones was also reported. These procedures allow the formation of N-aryl and N-alkyl indoles after subjecting the products to Fischer conditions for indole synthesis. 

Oxidative addition of a C-X bond to a metal is of centtal importance to organometallic chemistry and specially to its application in organic synthesis. Apart from the classic Grignard synthesis of RMgX and related species, a multitude of palladium catalyzed reactions (Mizoroki-Heck, Suzuki-Miyaura, Hartwig-Buchwald. ..) go by this initial step. 

The Buchwald-Hartwig palladium-catalyzed aryl-amino coupling reaction was applied to the synthesis of functionalized A-phenyl-2-quinolinones <03TL4207>. This was especially powerful because known methods of cyclization preclude anilines with electron-withdrawing groups para, or any ortho substituents, for steric reasons. 

A rather unusual procedure has been published for the palladium- and copper-catalyzed synthesis of triarylamines, using an alkaline water-ethanol emulsion stabilized by cetyltrimethylammonium bromide [41]. Anyway, this method overcomes the problem in the synthesis of N-aryl carbazoles (Eq. 14), which are not accessible by the method developed by Hartwig and Buchwald [42],... 

Buchwald et al. demonstrated that the intramolecular palladium-catalyzed C—O bond formation was an attractive means to assemble the oxygen heterocycles 557 (Scheme 170).243 They applied this methodology to the synthesis of MKC-242 (560), a benzodioxane antidepressant (Scheme 171).243b... 

Both Buchwald and Hartwig have explored the use of palladium-catalyzed amination for the synthesis of dendrimers and polyanilines. Dendrimers, such as 48, can be easily assembled through sequential aiylation of aminoanilines.89 These dendrimers are useful in creating metal-organic frameworks and often can exhibit interesting electronic effects, such as diradicals, and as optical materials. Polymeric anilines 49 are of intense interest due to their unique electrical conducting properties. Using the... 

Palladium-Catalyzed Indole Ring Synthesis Buchwald-Hartwig 621... 

The mechanism of the direct intramolecular Buchwald-Hartwig indole synthesis is that of a traditional palladium-catalyzed cross-coupling reaction and begins with loss of a ligand on palladium. Oxidative addition of an appropriately substituted Z-vinylhaloarene (1) generates intermediate 2. Deprotonation of 2 and displacement of a halide ligand sets up a reductive elimination on 3 to yield indole 4. 

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