Direct arylations

Direct Arylation (Written with Dr. Mark E. Scott, Dr. Dino Aiberico, and Prof. Mark tautens) 

Six mechanisms for the reaction of an arylmetal halide complex with an arene by iotermolecular and intramolecular processes. 

SCHEME 24.2 General mechanisms for Pd -catalyzed direct arylation. 

SCHEME 24.4 Representative examples for direct arylation using aryl bromides. 

SCHEME 24.5 Electronic effect for direct arylations using p-tolyl bromide. 

SCHEME 24.6 Base and additive effects on direct arylation of nitrobenzene. 

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Miura M, Nomura M (2002) Direct Arylation via Cleavage of Activated and Unactivated C-H Bonds. 219 211-241... 

Abstract This chapter highlights the use of iV-heterocyclic carbenes as supporting ligands in arylation reactions different than the more common cross-coupling reactions, including C-F bond activation, catalytic arylation, homocoupling, direct arylation and oxidative Heck reactions. 

Scheme 7.8 Direct arylation of 2-phenylpyiidine with NHC-Ru(II) complexes...

Scheme 7.9 Direct arylation using benzaldehyde as the directing group 7.5.1.2 Undirected Reaction...

Scheme 7.10 Direct arylation of phenyl hahdes and diphenylacetylene...

Fagnou and co-workers reported on the use of a palladium source in the presence of different phosphine ligands for the intramolecular direct arylation reaction of arenes with bromides [56]. Later, they discovered that new conditions employing palladium complex 27 promoted the direct arylation of a broad range of aryl chlorides to form six- and five-membered ring biaryls including different functionalities as ether, amine, amide and alkyl (Scheme 7.11) [57]. 

Scheme 7.11 Intramolecular direct arylation reactions with aryl chlorides...

The direct arylation of heteroaryls is particularly attractive due to the fact that these moieties are present in many biologically active compounds [58], Recently, etinkaya and co-workers reported the direct arylation of benzoxazoles and ben-zothiazoles with aryl bromides catalysed by a bis-NHC-palladium complex [59], Also, Sames and co-workers have described the C-H arylation of different SEM-protected heteroarenes, catalysed by NHC-Pd complex 28 (Scheme 7.12, pathway a) [60],... 

We have shown that the direct arylation of acrolein toward the synthesis of cinnamaldehyde derivatives was an efficient procedure. Using the palladacycle 1 as catalyst, substituted aldehydes 3 were prepared with up to 87% isolated yield from condensed aiyl bromides (Scheme 21.1, Route 1) that was extended successfully to heteroaiyl bromides, like bromoquinolines (6). Alternatively, the acrolein diethyl acetal was used as olefin and a selective formation of the saturated ester 4 was attained under the same reaction conditions (Scheme 21.1, Route 2). The expected aldehydes 3 were, however, obtained from most of the aiyl halides used under modified conditions. It was shown that the addition of n-Bu4NOAc in the medium... 

Under Lewis-acid-catalyzed conditions, electron-rich arenes can be added to alkenes to generate Friedel-Crafts reaction products. This subject will be discussed in detail in Chapter 7, on aromatic compounds. However, it is interesting to note that direct arylation of styrene with benzene in aqueous CF3CO2H containing H2PtCl6 yielded 30-5% zram-PhCH CHR via the intermediate PhPt(H20)Cl4.157 Hydropheny-lation of olefins can be catalyzed by an Ir(III) complex.158... 

Figure 2.12 Direct aryl-C-P bond formation in a bicyclic compound. 

Kerkvliet, N. I., Shepherd, D. M., and Baecher-Steppan, L., T lymphocytes are direct, aryl hydrocarbon receptor (AhR)-dependent targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) AhR expression in both CD4+ and CD8+ T cells is necessary for full suppression of a cytotoxic T lymphocyte response by TCDD, Toxicol. Appl. Pharmacol., 185, 146, 2002. 

Iridium-Catalyzed Direct Arylation of Aromatic C—H Bonds... 

Starting with iodobenzoic acids or iodobenzaldehydes and anilines, also a tandem Ugi-direct arylation (DAR) process is conceivable. In this manner, isoquino-lines 184 and 185 have been prepared [147,148] (Fig. 37). DAR has been exploited also as a tertiary transformation following an Ugi and a Buchwald-Hartwig A-arylation [62, 65]. 

Fagnou et al. reported the synthesis of mukonine (11) starting from methyl vanillate (644). This synthesis uses both a palladium(0)-catalyzed intermolecular direct arylation and an intramolecular cyclization reaction. Triflation of methyl vanillate (644) afforded the aryl triflate 645. Using a Buchwald-Flartwig amination protocol, the latter was subjected to direct arylation with 2-chloroaniline (646) to furnish the corresponding diarylamine 647. Finally, intramolecular cyclization of 647 afforded mukonine (11). To date, this is the best synthesis (three steps, 75% overall yield) available for mukonine based on commercially available methyl vanillate (644) (582) (Scheme 5.45). 

As mentioned above, condensed 1,2,3-triazine derivatives can be arylated by treatment with nitro-activated aryl halides. The only other report of direct arylation of the 1,2,3-triazine system is due to McKillop and Kobylecki, who studied the reaction of l,2,3-benzotriazin-4-one (10, R = H) with diaryliodonium salts in the presence of base. Treatment of 10, R = H, with diphenyl- and di-p-bromophenyliodonium chloride results in exclusive arylation at N2 and gives the corresponding triazinium betaines (77, R = Ph, p-BrCjH4) in good yield. When di-p-tolyliodonium chloride is used, a mixture of the Nj-, Nj-, and 0-arylated... 

Table 13. Arylated esters and ketones by direct arylation of siloxycyclopropanes (Ref. [57])...

The present method of preparation is that described by Bruggink and McKillop.4 It has the particular advantages of high yield and manipulative simplicity, and avoids the problem inherent in Hurt-ley s procedure of separation of mixtures of carboxylic acids by fractional crystallization or column chromatography. The method is, moreover, of wide applicability with respect to both the /3-dicarbonyl compound and the 2-bromobenzoic acid. The synthetic scope and limitations of this procedure for the direct arylation of... 

Aryl halides normally do not react with phosphines. However, under forcing temperature conditions, most frequently at 170-250 °C in the absence of solvents, it is possible to achieve direct arylation of tertiary phosphines by several halogenated aromatic or heteroaromatic compounds, especially when they are activated26 (reactions 20 and 21). New examples of such arylations have been described for nitrogen heterocycles255 256,... 

A systematic investigation of the copper-catalyzed reaction between 2-bromobenzoic acid and the anions of 1,3-dicarbonyl compounds has established the optimum conditions for the direct arylation of the /3-dicarbonyl moiety (75T2607). The use of sodium hydride as the base and copper(I) bromide as catalyst is recommended. The absence of a protic solvent ensures that competitive attack on the bromobenzoic acid by a solvent-derived base leading to a salicylic acid is eliminated. For larger scale reactions the addition of toluene offers some practical advantages. 

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