Direct arylation, metal-catalyzed

Although the direct arylation reactions catalyzed by transition metal complexes (other than palladium) are discussed in this chapter, the corresponding palladium-catalyzed transformations are summarized in Chapter 10. A detailed overview of the mechanistic aspects of metaldirect arylations is provided in Chapter 11. 

Over the last few years, functionalization by means of C—H activation has gained considerable importance for several reasons, including atom economy, the drastic decrease of undesired by-products, and reduced costs for the preparation of substrates, which are often available in fewer steps. In this respect, recent efforts were devoted to the elaboration of efficient protocols for the direct transition metal-catalyzed aryl-aryl bond formation of nonactivated aromatic snbstrates [63, 68, 69]. 

Direct aromatic substitution of unactivated aryl halides is slow and generally requires a catalyst to become a useful synthetic method. Copper reagents have been used in some cases in classical procedures for the formation of products from aromatic substitution. In many cases these copper-mediated reactions occur at high temperatures and are substrate dependent. Since the 1970s, transition metal catalysts have been developed for aromatic substitution. Most of the early effort toward developing metal-catalyzed aromatic substitution focused on the formation of... 

This chapter mainly treats transition metal-catalyzed direct functionalization of carbon-hydrogen bonds in organic compounds. This methodology is emphasized by focusing on important functionalizations for synthetic use. The contents reviewed here are as follows (i) alkylation of C-H bonds, (ii) alkenylation of C-H bonds, (iii) arylation of C-H bonds, (iv) carbonylation of C-H bonds, (v) hydroxylation and the related reactions, and (vi) other reactions and applications. 

Substituted imidazole 1-oxides 228 are predicted to be activated toward electrophilic aromatic substitution, nucleophilic aromatic substitution, and metallation as described in Section 1. Nevertheless little information about the reactivity of imidazole 1-oxides in these processes exists. The reason for this lack may be the high polarity of the imidazole 1-oxides, which makes it difficult to find suitable reaction solvents. Another obstacle is that no method for complete drying of imidazole 1-oxides exists and dry starting material is instrumental for successful metallation. Well documented and useful is the reaction of imidazole 1-oxide 228 with alkylation and acylation reagents, their function as 1,3-dipoles in cycloadditions, and their palladium-catalyzed direct arylation. 

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. 

Abstract Azines, diazines or thiazole (V-oxides are highly reactive substrates in palladium-catalyzed direct arylation reaction. For these reactions, the results are inconsistent with an SEAr reaction pathway and may best fit with a concerted metalation-deprotonation-like (CMD) mechanism. 

Ongoing research in our group and by others [62-65] on the mechanism of palladium-catalyzed direct arylation has led to the advancement of a second mode of C-H bond cleavage where a Wheland-like intermediate is not involved in the reaction pathway (Scheme 4). This pathway, which we have termed a concerted metalation-deprotonation (CMD) mechanism, appears less dependent on arene... 

Over the past decade, significant advances have been made in the transition-metal-catalyzed aryl-aryl bond formation through C-H activation (for reviews see [23-32]). In this direct arylation reaction one of the preactivated reaction partners is replaced by a simple arene. This direct arylation process is not only just of academic interest but also attractive for industrial applications, since only one preactivated reaction partner is needed. Obviously, the cost of the reaction will be reduced by... 

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