Palladium-Catalyzed C-H Olefination

Palladium-catalyzed C-H olefination is also a very useful protocol to synthesize oxygen-containing heterocycles, since it allows to functionalize the substrates with an unsaturated olefinic moiety which would constitute a Jt-conjugated structure or be elaborated further. Two pathways are often encountered in this approach (i) addition of the resulted arylpalladium complex to alkynes and subsequent protonation or transformation and (ii) addition of the arylpalladium complex to olefins and following palladium hydride elimination [7b, 20]. The current methods are mainly focused on the functionalization of aromatic C-H bonds to form benzo-oxacycles. 

It is known that alkynes could readily interact with transition metals to form q -metal complexes and then undergo further elaboration [27] thus alkynes should be potentially useful in the ortho-aroimtic C-H olefination to form oxygen-containing heterocycles. In 2012, Minami and Hiyama reported a palladium-catalyzed cycloaddition of alkynyl aryl ethers to give internal alkynes 

The aforementioned methods to construct benzofurans are all achieved by activation of C(sp )-H bond. In 2012, based on the alkynoxy-directed synthesis of 2-methylidene-2H -chromene derivatives [28], Hiyama and coworkers developed a palladium-catalyzed hydrobenzylation of ortho-tolyl alkynyl ethers to construct 2-methylidene-2,3-dihydrobenzofurans via the activation of benzylic C(sp )-H bond [34]. 

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Phenol and its derivatives are the most common substrates for the construction of oxacycles in this approach. In 2000, Fujiwara and coworkers reported a palladium-catalyzed intramolecular addition reaction of aryl alkynoates to construct coumarins in a mixture of trrfluoroacetic acid and CH2CI2 at room temperature (Scheme 3.6) [21]. This method is simple and efficient to give the desired oxygen-containing heterocycles in high yields. However, this palladium-catalyzed C-H olefination reaction is only constrained to the electron-rich aromatic compounds owing to the inherent limitation of electrophilic metalation process. 

As a further modification of Fujiwara s work, Kitamura and coworkers realized the construction of coumarins by palladium-catalyzed C-H olefination of phenols with acrylates and subsequent intramolecular esterification (Scheme 3.7)... 

Palladium-catalyzed oxidative allylic C-H functionalization provides attractive methods for the transformations of olefins, and their utility can be further enhanced by the development of more effective ways to use molecular oxygen (or air) to promote the catalytic cycle. The results outlined in this chapter summarize significant progress in the coupling reaction between terminal alkene and various types of nucleophiles. Further studies will be directed to explorations of the scope of nucleophilic reagents and olefins, and elucidation of the mechanisms of those reactions. Such studies will play an important role in the ongoing development of Pd-catalyzed C-H bond activations. 

The palladium-catalyzed preparation of vinyl ethers through a tandem reaction consisting of an initial C—H olefination of a tertiary alcohol by an activated alkene followed by an intramolecular oxidative cychzation has been achieved using a palladium catalyst and an unusual supporting ligand (Scheme 2.107) [154]. This ligand was a leucine derivative... 

Besides six-membered heterocycles, the construction of five-membered analogs by C-H olefination of phenol derivatives has also been reported. In 2011, Wang and coworkers reported a palladium-catalyzed oxidative cyclization of 3-phenoxy acrylates to construct benzofurans via an intramolecular aromatic C-H olefination (Scheme 3.13) [31]. In the presence of 5 mol% Pd(OAc)2/PPh3 and 2.0 equiv. of CF3C02Ag, benzofurans were obtained in good yields in... 

Shi W, Luo Y, Luo X, Chao L, Zhang H, Wang J, Lei A (2008) Investigation of an efficient palladium-catalyzed C(sp)-C(sp) cross-coupling reaction using phosphine-olefin ligand application and mechanistic aspects. J Am Chem Soc 130 14713-14720... 

Conventionally, organometallic chemistry and transition-metal catalysis are carried out under an inert gas atmosphere and the exclusion of moisture has been essential. In contrast, the catalytic actions of transition metals under ambient conditions of air and water have played a key role in various enzymatic reactions, which is in sharp contrast to most transition-metal-catalyzed reactions commonly used in the laboratory. Quasi-nature catalysis has now been developed using late transition metals in air and water, for instance copper-, palladium- and rhodium-catalyzed C-C bond formation, and ruthenium-catalyzed olefin isomerization, metathesis and C-H activation. Even a Grignard-type reaction could be realized in water using a bimetallic ruthenium-indium catalytic system [67]. 

Poly(ethylene oxide) polymers and poly(ethylene oxide/propylene oxide) copolymers with iminodipropionitrile (139) or iminodiacetonitrile end groups were used as ligands in the palladium-catalyzed oxidation of higher olefins (1-octene to 1-hexadecene) at 50-70 °C with atmospheric air or 1-3 bar O2. In an ethanol/water mixture 88 % yield of 2-hexanone and 92 % yield of 2-hexadecanone was obtained in 4 and 2 h, respectively, with a... 

Wacker reactions, which is why we refer to them here [12, 15-17]. Finally, the general concept of a Wacker reaction could be regarded as the palladium-catalyzed oxidative coupling of heteronucleophiles and olefins, and this can obviously be extended to nitrogen nucleophiles and others [18] conversely, the principle of the Cu(I)/Cu(II)/02 reoxidation system for Pd(0) can be applied to other oxidation reactions (for example that of CO to C02), but the present overview is limited to sp2-C-H activation in olefins. 

M. Beller, A. Zapf, and T. H. Riermeier, Palladium-Catalyzed Olefinations of Aryl Halides (Heck Reaction) and Related Transformations, in Transition Metals for Organic Synthesis, Second Ed. (Eds. M. Beller and C. Bolm, Wiley-VCH, Weinheim, 2004, Vol. 1, Chap. 2.13). 

We reported that the palladium-catalyzed reaction of arynes with bis-jr-allyl palladium complex afforded 1,2-diallylated derivatives of benzene in good yields (Scheme 32) [77]. The reaction of 104 with allyltributylstan-nane 3a and allyl chloride 11 in acetonitrile in the presence of 2.5 mol % Pd2(dba)3.CHCl3/dppf catalyst at 40 °C for 12 h afforded 1,2-diallyl benzene 105 in 76% yield. The generation of benzyne 106 takes place presumably first from 104 under the conditions of the palladium catalysis, which reacts with the complex 2 in a manner similar to the diallylation of activated olefins (refer Scheme 29). 

As already mentioned for rhodium carbene complexes, proof of the existence of electrophilic metal carbenoids relies on indirect evidence, and insight into the nature of intermediates is obtained mostly through reactivity-selectivity relationships and/or comparison with stable Fischer-type metal carbene complexes. A particularly puzzling point is the relevance of metallacyclobutanes as intermediates in cyclopropane formation. The subject is still a matter of debate in the literature. Even if some metallacyclobutanes have been shown to yield cyclopropanes by reductive elimination [15], the intermediacy of metallacyclobutanes in carbene transfer reactions is in most cases borne out neither by direct observation nor by clear-cut mechanistic studies and such a reaction pathway is probably not a general one. Formation of a metallacyclobu-tane requires coordination both of the olefin and of the carbene to the metal center. In many cases, all available evidence points to direct reaction of the metal carbenes with alkenes without prior olefin coordination. Further, it has been proposed that, at least in the context of rhodium carbenoid insertions into C-H bonds, partial release of free carbenes from metal carbene complexes occurs [16]. Of course this does not exclude the possibility that metallacyclobutanes play a pivotal role in some catalyst systems, especially in copper-and palladium-catalyzed reactions. 

Interestingly, Widenhoefer reported a similar palladium(II) catalyzed cycliza-tion of indoles onto alkenes (Scheme 58) [72]. This mild protocol for cyclization/ carboxylation of 2-alkenyl indoles makes possible catalytic addition of a carbon-nucleophile and carbonyl group across a C-C bond. The mechanism, however, is thought to involve outer-sphere attack of indole onto a palladium-olefin complex rather than the electrophilic C-H activation of the indole C(3)-H bond, exhibited by the Stoltz carbocyclization. 

Palladium-Catalyzed Allylic C-H Bond Functionalization of Olefins... 

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