Palladium catalysis arylation/oxidation

C-H borylation is a widely used methodology for the synthesis of organoboronates [63-65]. Most of the applications have been presented for the synthesis of aryl-boronates. However, functionalization of alkenes has also attracted much interest [66, 67]. In most applications, iridium catalysis was used. However, in case of alkenes, borohydride forms as a side product of the C-H borylation, which undergoes hydroboration with alkenes. This side reaction can be avoided using palladium catalysis under oxidative conditions. In a practically useful implementation of this reaction, pincer-complex catalysis (Ig) was appHed (Figure 4.17) [51]. The reaction can be carried out under mild reaction conditions at room temperature using the neat aUcene 34 as solvent. In this reaction, hypervalent iodine 36, the TFA analog of 29, was employed. In the absence of 36, borylation reaction did not occur. 

The intramolecular arylation of sp3 C-H bonds is observed in the reaction of l-/ r/-butyl-2-iodobenzene under palladium catalysis (Equation (71)) 94 94a 94b The oxidative addition of Arl to Pd(0) gives an ArPdl species, which undergoes the electrophilic substitution at the tert-butyl group to afford the palladacycle. To this palladacycle, another molecule of Arl oxidatively adds, giving the Pd(iv) complex. 

Other unsaturated substrates arylated by various diaryl iodonium salts included butenone, acrylic acid, methyl acrylate and acrylonitrile [46]. Allyl alcohols with diaryliodonium bromides and palladium catalysis were arylated with concomitant oxidation for example, from oc-methylallyl alcohol, aldehydes of the general formula ArCH2CH(Me)CHO were formed [47]. Copper acetylide [48] and phenyl-acetylene [49] were also arylated, with palladium catalysis. 

O/t/20-arylation of benzoic acids is often preferable to ortho-arylation of benzamides if conversion of the amide moiety to other functional groups is desired. However, only a few reports have dealt with the orf/io-functionalization of free benzoic acids due to challenges that involve such transformations. The reactions can be complicated by decarboxylation of the product and the starting material. Despite those difficulties, several methods for direct o/t/io-arylation of benzoic acids have been developed. Yu has shown that arylboronates are effective in arylation of benzoic acids under palladium catalysis [59], The reactions require the presence of palladium acetate catalyst, silver carbonate oxidant, and benzoquinone. Even more interestingly, the procedure is applicable to the arylation of unactivated sp3 C-H bonds in tertiary carboxylic acids such as pivalic acid (Scheme 13) if aryl iodide coupling partner is used. Aryl trifluoroborates can also be used [60],... 

The most common means of activating aromatic C-H bonds via palladium catalysis is by electrophilic C-H activation. This proceeds more like a Freidel-Craft type metahation mechanism, followed by rearomatization to form versatile aryl-metal intermediates (Scheme 5) [19]. It can occur with electrophilic palladium(II) catalysts such as Pd(OAc)2, PdCl2, Pd(TFA)2 (Scheme 5a) or on electrophilic aryl-pahadium(II) complexes, that result from oxidative addition of palladium(O) into an aryl halide (Scheme 5b). The resultant aryl-palladium(H) complexes are analogous to those observed in conventional cross-coupling reactions and as such are versatile intermediates in the formation of new C-C bonds. 

Aryl iodides are more reactive towards oxidative addition than aryl bromides, and a selective Heck coupling (without phosphine ligands) with an unsaturated side chain left the bromide in place. A second Heck reaction of this bromide with an allylic alcohol was used to introduce a second side chain. Cyclization of the amide on to the allylic alcohol was achieved with palladium catalysis, not as might have been expected with palladium(O) but instead with palladium(ll), to produce the seven-membered ring. Finally, the conjugated double bond was reduced and the sulfonamide removed under photolytic conditions. 

Zinc Derivatives. Zincated and Al-protected 6-iodouracil 155 can be used under Negishi conditions for the preparation of 6-arylated uracil derivatives (Scheme 63). The conversion of the 6-iodouracil derivative is best performed using highly active zinc dust in DMAC.f The oxidative addition of active zinc has also been applied to a number of other iodo- and bromo-substituted 7r-deficient heteroarenes such as pyridine, pyrimidine, and quinoline, giving the corresponding heteroarylzinc halides 156, which are transformed to arylated derivatives by palladium catalysis. ... 

Oestxeich found that the direct arylation of indolines could be accomplished without over oxidation to the corresponding indole under palladium-catalysis with air (open flask), oxygen (balloon), or copper(II) acetate as the oxidant. Indolines can be unsubstituted or substituted as C2/C3 and the reaction performs well on gram scale (250, 18 examples, 18—90% isolated yield) (140L6020).A directed C2-functionalization/C7-alkenylation was discovered by Xu,Yi, and colleagues. With a rhodium catalyst, indole derivatives were functionalized with acetates at C2 (22 examples, 62—92% yield) the newly obtained products could be alkenylated at C7 with a rhodium/copper system (251,3 examples, 68—78% yield) (14CC6483). 

Several studies have used palladium catalysis in the arylation of benzoxazoles. A palladium catalyst with a phosphine ligand allows their reaction with aryl mesylates without the requirement for acid or copper additives. In the reaction with arene-sulfonyl chloride, palladium is used in combination with copper. A plausible mechanism involves initial cupration of the benzoxazole followed by copper—palladium exchange and oxidative addition of the sulfonyl chloride to palladium to give (84). This intermediate may lose sulfur dioxide to give an aryl palladium species, which, on reductive elimination, yields 2-arylbenzoxazole. The arylation of benzoxazoles and benzthiazoles with aryl boronic acids is also catalysed by a combination of palladium... 

The same group reported 1 year later that aromatic imines can also be ortho arylated under similar conditions, and the resulting imine was hydrolyzed during acidic workup to the corresponding ketone (Eq. 4) [24]. The C-H bond was preferentially functionalized in the presence of a reactive bromide, triflate, or tosylate group, in contrast with palladium catalysis, where the halide reacts selectively (Eq. 5). Nakamura group also demonstrated that dioxygen can be used as an alternative oxidant, albeit the reaction efficiency decreased [25]. 

While furans have been the main focus of palladium-catalyzed allene cycloisomerization, pyrroles can also be generated via reaction of allenyl-substituted amines. A number of metal catalysts have been reported to mediate the cyclization of these substrates to pyrrolines, however, the use of palladium catalysis can allow the concomitant incorporation of aryl functionality into the 3-position, as shown in Scheme 6.27. At elevated temperatures, oxidation of the pyrroline occurs to afford pyrroles [37]. 

It was shown that palladacydes 1 [3c, 24] prepared from palladium] I) acetate and tris(o-tolyl)- or trimesitylphosphine are excellent catalysts for the Heck coupHng of triflates and halides including certain aryl chlorides. In some of these cases, a possible involvement of oxidation states +II and +IV in the catalytic cycle has been considered [25]. Similarly, other palladacydes such as 3 [26e,h] or 6 [27] have been used in the Heck reactions (Figure 8.1) [24, 26, 28]. It has been proposed that, at least for NC palladacydes, the reaction proceeds through the classical phosphine-free Pd(0)/Pd(II) catalytic cycle and that the active catalysts are actually slowly formed palladium clusters [29]. Besides classical palladacydes, complexes with pincer-type ligands such as 2 [30] have become very popular in palladium catalysis [31]. 

Notably, Rieke manganese is able to take part in oxidative addition even where Rieke zinc or Rieke magnesium is insufficiently reactive [258]. The 3-thienylmanganese bromide intermediate 123 can be coupled effectively with both aryl iodides and aroyl chlorides via palladium catalysis to give the products 124 and 125 in moderate to high yields (Scheme 50, Table 28) [343, 344],... 

Themechanismof the Pd° coupling presumably proceeded via the typical oxidative addition of the aryl iodide to Pd to give a palladium (H) intermediate. Subsequent metathesis of the Pd (ip intermediate with die F-vinyl zinc reagent followed by reductive elimination gave the aryl-substituted ole and regenerated the Pd catalyst as summarized below for a typical palladium catalysis cycle. 

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