Aryl triflates oxidative addition

Tandem cyclization/3-substitution can be achieved starting with o-(trifluoro-acetamido)phenylacetylenes. Cyclization and coupling with cycloalkenyl trif-lates can be done with Pd(PPh3)4 as the catalyst[9]. The Pd presumably cycles between the (0) and (II) oxidation levels by oxidative addition with the triflate and the reductive elimination which completes the 3-alkenylation. The N-protecting group is removed by solvolysis under the reaction conditions, 3-Aryl groups can also be introduced using aryl iodides[9]. 

The Stille coupling of an aryl triflate normally calls for the addition of at least one equivalent of LiCl. Presumably, the transmetallation is facilitated by replacing triflate with CP at the palladium intermediate generated from oxidative addition. As Stille demonstrated in 1988, 4-quinolinyl triflate 100 was coupled with phenylstannane 101 in the presence of Pd(Ph3P)4 and LiCl in refluxing 1,4-dioxane to furnish biaryl 102, which was used as an intermediate for the first total synthesis of antibiotic amphimedine (88JA4051). 

This reaction is not a bona fide Heck reaction per se for two reasons (a) the starting material underwent a Hg Pd transmetallation first rather than the oxidative addition of an aryl halide or triflate to palladium(O) (b) instead of undergoing a elimination step to give an enone, transformation 134 136... 

Intramolecular arylation of G-H bonds gives cyclic aromatic compounds. In this intramolecular arylation, the carbon-palladium cr-bond is first formed by the oxidative addition of Pd(0) species and then the resulting electrophilic Pd(n) species undergoes the intramolecular G-H bond activation leading to the formation of the palladacycle, which finally affords the cyclic aromatic compounds via reductive elimination.87 For example, the fluoroanthene derivative is formed by the palladium-catalyzed reaction of the binaphthyl triflate, as shown in Scheme 8.88 This type of intramolecular arylation is applied to the construction of five- and six-membered carbocyclic and heterocyclic systems.89 89 89 ... 

Vinyl- [64] and aryl triflates [65] as pseudo organic halides readily couple with stannylpyridines as long as more than one equivalent of LiCl is present in the reaction mixture. Presumably, the transmetalation is facilitated by replacing triflate with Cl at the palladium intermediate generated from oxidative addition. For example, 2-(benzopyran-4-yl)pyridine 80 was obtained from treatment of vinyl triflate 79 with 2-trimethylstannylpyridine in the presence of Pd2(dba)3(CHCl3)-Ph3P and LiCl [64],... 

The basic mechanism of the Stille reaction involves transmetallation, either directly or via an organocopper intermediate, with a Pd(H) intermediate generated by oxidative addition from the aryl halide or triflate. 

The overall mechanism is closely related to that of the other cross-coupling methods. The aryl halide or triflate reacts with the Pd(0) catalyst by oxidative addition. The organoboron compound serves as the source of the second organic group by transmetala-tion. The disubstituted Pd(II) intermediate then undergoes reductive elimination. It appears that either the oxidative addition or the transmetalation can be rate-determining, depending on reaction conditions.134 With boronic acids as reactants, base catalysis is normally required and is believed to involve the formation of the more reactive boronate anion.135... 

Normally, the most practical vinyl substitutions are achieved by use of the oxidative additions of organic bromides, iodides, diazonium salts or triflates to palladium(0)-phosphine complexes in situ. The organic halide, diazonium salt or triflate, an alkene, a base to neutralize the acid formed and a catalytic amount of a palladium(II) salt, usually in conjunction with a triarylphosphine, are the usual reactants at about 25-100 C. This method is useful for reactions of aryl, heterocyclic and vinyl derviatives. Acid chlorides also react, usually yielding decarbonylated products, although there are a few exceptions. Likewise, arylsulfonyl chlorides lose sulfur dioxide and form arylated alkenes. Aryl chlorides have been reacted successfully in a few instances but only with the most reactive alkenes and usually under more vigorous conditions. Benzyl iodide, bromide and chloride will benzylate alkenes but other alkyl halides generally do not alkylate alkenes by this procedure. 

As noted for the Heck reaction, aryl, alkenyl, and alkynyl bromides, iodides, and triflates are best for the oxidative addition. However, aromatic, heteroaromatic, alkenyl, and even alkyl boronic acids and esters can be coupled effectively. The reaction appears almost oblivious to other functional groups present ... 

Stille coupling was also developed in tlie early 1980s and is similar to Suzuki coupling in its sequence. It is used to couple aryl or vinyl halides or triflates with organotin compounds via oxidative addition, transmetallation, and reductive elimination. The oxidative addition reaction has tlie same requirements and preferences as discussed earlier for tlie Heck and Suzuki reactions. The reductive elimination results in formation of tlie new carbon-carbon bond. The main difference is that tlie transmetallation reaction uses an organotin compound and occurs readily without the need for an oxygen base. Aryl, alkenyl, and alkyl stannanes are readily available. Usually only one of tlie groups on tin enters into... 

Mesylates are used for Ni-catalysed reactions. Arenediazodium salts 2 are very reactive pseudohalides undergoing facile oxidative addition to Pd(0). They are more easily available than aryl iodides or triflates. Also, acyl (aroyl) halides 4 and aroyl anhydrides 5 behave as pseudohalides after decarbonylation under certain conditions. Sulfonyl chlorides 6 react with evolution of SO2. Allylic halides are reactive, but their reactions via 7t-allyl complexes are treated in Chapter 4. Based on the reactions of those pseudohalides, several benzene derivatives such as aniline, phenol, benzoic acid and benzenesulfonic acid can be used for the reaction, in addition to phenyl halides. In Scheme 3.1, reactions of benzene as a parent ring compound are summarized. Needless to say, the reactions can be extended to various aromatic compounds including heteroaromatic compounds whenever their halides and pseudohalides are available. 

Ni(0) complexes react with halides and pseudohalides. Their reactions are somewhat different from those of Pd(0). Chlorides add to Ni(0) much more easily than to Pd(0). Even C—O bonds such as aryl alkyl ether bonds are cleaved with Ni(0) under certain conditions. Not only triflates, but also mesylates react with Ni(0). Oxidative addition to Ni(0) and subsequent transformations are summarized in Scheme 3.6. 

Fig. 16.1. Presumed elementary steps of a C,C coupling between a Gilman cuprate and an alkenyl or aryl triflate (X = 03S—CF3), bromide (X = Br), or iodide (X = I). The four elementary steps of the reaction, discussed in the text, are (1) complexation, (2) oxidative addition of the substrate to the metal, (3) reductive elimination, and (4) dissociation of the w-bound ligand.

In step 1 of Figure 16.18, one of the above-mentioned Pd(0) complexes, Pd(PPh3)3 or Pd(PPh3)2, forms a -complex with the aryl triflate. Step 2 is an oxidative addition. The Pd inserts into the Cs —O bond of the aryl triflate and the oxidation number of Pd increases from... 

The initial step of the catalytic cycle is oxidative addition of aryl triflate to a BINAP-coordinated Pd(0) species. Since, in the actual catalytic system, Pd(OAc)2 and (/ )-BINAP are used as the precursors of the Pd(0) species, reduction of Pd(OAc)2 into the BINAP-coordinated Pd(0) species should be operative prior to the catalytic reaction. Although Pd(OAc)2 is the most commonly used precursor of a Pd(0) species in many palladium-catalyzed organic reactions, no direct information has been reported so far on its reduction process. In this study, we confirmed for the first time that the reduction proceeds according to the process involving a combination of tertiary phosphine (BINAP) and water as the reducing reagent (Scheme 8) (Ozawa, F. Kubo, A. Hayashi, T., submitted for publication). 

Especially for alkyl halides 6 the transfer of a single electron from the metal center is facile and occurs at the halide via transition state 6C, which stabilizes either by direct abstraction of the halide to a carbon-metal complex radical pair 6D or via a distinct radical anion-metal complex pair 6E. This process was noted early but not exploited until recently (review [45]). Alkyl tosylates or triflates are not easily reduced by SET, and thus Sn2 and/or oxidative addition pathways are common. The generation of cr-radicals from aryl and vinyl halides has been observed, but is rarer due to the energy requirement for their generation. Normally, two-electron oxidative addition prevails. 

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