Heteroarenes with boronic acids

Similarly, the palladium-catalyzed reaction of indoles and other electron-rich arenes with aryl boronic acids was proposed to take place by an electrophilic aromatic substitution, presumably by an initial paUadation of the arene or heteroarene followed by a transmetallation process [76]. In this reachon, C-2 arylation was exclusively observed. 

An interesting selectivity was uncovered in the direct cross-dehydrogenative coupUng between N-protected indoles and arenes (Scheme 11.40) [151]. Thus, whereas 2-arylated indoles 67a were preferentially obtained from N-acetyhndole in the presence of Cu(OAc)2, the reaction of N-pivalolyUndole with AgOAc led to 67b, with excellent selectivities. The reason for this C-2/C-3 selectivity is most likely due to the formation of higher-order palladium clusters or paUadium/copper clusters under the different reaction conditions. A related reaction between aryl-boronic acids and arenes or heteroarenes also proceeds under oxidative conditions with Pd(OAc)2 as catalyst [76]. A catalytic cycle initiated by an electrophihc attack of Pd(II) on the arene, followed by transmetallation with the aryl boronic acid and reductive elimination, was suggested. In this transformation, Cu(OAc)2 as stoichiometric oxidant could be replaced by O2, and for indoles, arylation at C-2 was observed. 

The iron-catalysed reaction of heteroarenes, including indoles, pyrroles, thiophene, and furan, with 3-methyl-2-quinonyl boronic acids allows the formation of alkylated products, such as (68), rather than the more usual alkenylated products. The unusual alkylation, at the 5-position, of oxindoles to give products such as (69) has been reported using the acid-catalysed reaction with benzylic alcohols in nitromethane. Silylation of indole, at the 3-position, to give (70) has been achieved using a cationic ruthenium(II) sulfide complex as a catalyst. A sulfur-stabilized silicon electrophile is formed resulting in a Wheland intermediate which is deprotonated by sulfur atom. ... 

Hu and Yu reported an iron/macrocyclic polyamine-catalyzed reaction of arylboronic acids with a large excess of pyrrole or pyridine at 130°C tmder air (Eqs. 26 and 27) [63], based on their previous studies on iron-mediated reactions (initial report using a stoichiometric amount of iron [64]). Pyrrole derivatives were arylated at 2-position in good yield (Eq. 26), but when pyridine was used as a substrate, the catalyst turnover was poor and 2-arylpyridine was obtained together with a small amount of 3-aryl- and 4-arylpyridine (Eq. 27). Because a catalytic amotmt of a radical scavenger did not inhibit the reaction, the authors proposed an oxoiron complex as the active species to activate the ort/io-hydrogen of the heterocycle via o-bond metathesis and also performed a DPT analysis of the mechanism. A related iron-catalyzed reaction of aryl boronic acids with heteroarenes was reported by Singh and Vishwakarma [65]. 

Boron derivatives of heteroarenes are also viable partners. A Suzuki reaction of a vinyl triflate 2.282, prepared by enantioselective enolate formation, with a benzothiophenyl boronic acid 2.283 was used to prepare 12.75 kg of a tropane derivative 2.284 (as its tartrate salt) as a drug candidate (Scheme 2.90). ... 

Kita and coworkers developed an efficient synthesis of aiyl(phenyl)iodonium tosylates from HTIB and arenes in TFE at room temperature [29, 30]. This type of iodonium salt is chemoselectively employed in metal-free syntheses of biaryls (see Sect. 4.2.1). The synthetic strategy has been employed, for example, in the synthesis of polyfluorinated At21X [81] and acid-labile boron-substituted diaryliodonium salts firom aryl boronates with HTIB or the reagent combination PIFA/AcOH (Scheme 4a) [82]. Suna and coworkers have recently described the synthesis of heteroaryl(aryl)iodonium salts from heteroarenes and [hydroxy(tosyloxy)iodo] mesitylene or DIB combined with TsOH or AcOH. The salts were either isolated or used in situ (see Sects. 3.1.2 and 3.2.2) because of their relative instability [83, 84]. (Diacetoxyiodo)arenes were recently combined with electron-donating arenes and trimethylsilyl triflate (TMSOTf) to provide unsymmetric iodonium trifiates without the need for acid addition [85]. 

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