Palladium-catalyzed amination hydrazones

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. 

Watanabe reports a new method for the direct conversion of o-choroacetaldehyde N,N-disubstituted hydrazones into 1-aminoindole derivatives 93 by palladium-catalyzed intramolecular ring closure of 92 in the presence of P Bu3 or the bisferrocenyl ligand 94 <00AG(E)2501>. When X = Cl, this cyclizative process can be coupled with other Pd-catalyzed processes with nucleophilic reagents (e.g., amines, azoles, aryl boronic acids) so as to furnish indole derivatives with substituents on the carbocyclic ring. 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

Recently, l-aryl-l//-indazoles have been prepared via palladium-catalyzed intramolecular amination of aryl halides. For example, the bromo-aryl-hydrazone cyclized to give the corresponding indazole under the influence of a palladium catalyst in the presence of a base. 

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