Alkyne palladium-catalyzed, mechanism

Scheme 5-18 Stoichiometric reactions relevant to the proposed mechanism for palladium-catalyzed hydrophosphonylation of alkynes...

Scheme5-24 Eq. (1) Proposed mechanism for Eq. (2) Stoichiometric reactions relevant to the phosphinic acid-modified palladium-catalyzed proposed mechanism hydrophosphinylation of alkynes.

This reaction typifies the two possibilities of reaction routes for M-catalyzed addition of an S-X (or Se-X) bond to alkyne (a) oxidative addition of the S-X bond to M(0) to form 94, (b) insertion of alkyne into either the M-S or M-X bond to provide 95 or 96 (c) C-X or C-S bond-forming reductive elimination to give 97 (Scheme 7-21). Comparable reaction sequences are also discussed when the Chalk-Harrod mechanism is compared with the modified Chalk-Harrod mechanism in hydrosily-lations [1,3]. The palladium-catalyzed thioboratiori, that is, addition of an S-B bond to an alkyne was reported by Miyaura and Suzuki et al. to furnish the cis-adducts 98 with the sulfur bound to the internal carbon and the boron center to the terminal carbon (Eq. 7.61) [62]. 

Hydroarylations of alkynes are catalyzed by gold complexes and these bear some resemblance to the Fujiwara Pd-catalyzed reaction. In general, when using gold chemistry, better Z/E selectivities are observed compared with palladium, lower catalyst loadings and milder conditions (neutral not TFA) are used. The mechanism involves the attack of ArH on the Au-coordinated alkyne. Flowever, electron-poor acetylenes only appear to work with palladium chemistry (Equations (75) and (76)).72... 

In analogy to the mechanism of the palladium-catalyzed enyne cyclization, it is postulated that exposure of palladium(O) to acetic acid promotes in situ generation of hydridopalladium acetate LnPd"(H)(OAc). Alkyne hydrometallation affords the vinylpalladium complex A-10, which upon r-carbopalladation of the appendant alkyne provides intermediate B-7. Silane-mediated cleavage of carbon-palladium bond liberates the cyclized product along palladium(O), which reacts with acetic acid to regenerate hydridopalladium acetate to close the cycle (Scheme 33). 

Disubstituted silole derivatives are synthesized by the palladium-catalyzed reaction of (trialkylstannyl)di-methylsilane with terminal alkynes (Equation (107)).266 The mechanism is supposed to involve a palladium silylene complex, which is generated via /3-hydride elimination from LJ3d(SiMe2H)(SnBu3) (Scheme 62). Successive incorporation of two alkyne molecules into the complex followed by reductive elimination gives rise to the silole products. 

Unsubstituted or 2,3-disubstituted stannoles can be prepared from the palladium-catalyzed reaction of an alkyne with the stable stannylenes [(Me3Si)2CH]2Sn and CH2C(SiMe3)2 2Sn . The mechanism has been traced by the isolation of intermediates,235 and by ab initio calculations (Equation (78)).236... 

Particularly interesting is the reaction of enynes with catalytic amounts of carbene complexes (Figure 3.50). If the chain-length between olefin and alkyne enables the formation of a five-membered or larger ring, then RCM can lead to the formation of vinyl-substituted cycloalkenes [866] or heterocycles. Examples of such reactions are given in Tables 3.18-3.20. It should, though, be taken into account that this reaction can also proceed by non-carbene-mediated pathways. Also Fischer-type carbene complexes and other complexes [867] can catalyze enyne cyclizations [267]. Trost [868] proposed that palladium-catalyzed enyne cyclizations proceed via metallacyclopentenes, which upon reductive elimination yield an intermediate cyclobutene. Also a Lewis acid-catalyzed, intramolecular [2 + 2] cycloaddition of, e.g., acceptor-substituted alkynes to an alkene to yield a cyclobutene can be considered as a possible mechanism of enyne cyclization. 

Ahlquist, M. Fabrizi, G. Cacchi, S. Norrby, P.-O. The Mechanism of the Phosphine-Free Palladium-Catalyzed Hydroarylation of Alkynes. J. Am. Chem. Soc. 2006, 128, 12785-12793. 

Yamamoto has proposed a mechanism for the palladium-catalyzed cyclization/hydrosilylation of enynes that accounts for the selective delivery of the silane to the more substituted C=C bond. Initial conversion of [(77 -C3H5)Pd(GOD)] [PF6] to a cationic palladium hydride species followed by complexation of the diyne could form the cationic diynylpalladium hydride intermediate Ib (Scheme 2). Hydrometallation of the less-substituted alkyne would form the palladium alkenyl alkyne complex Ilb that could undergo intramolecular carbometallation to form the palladium dienyl complex Illb. Silylative cleavage of the Pd-G bond, perhaps via cr-bond metathesis, would then release the silylated diene with regeneration of a palladium hydride species (Scheme 2). 

In the alkyne dimerization catalyzed by palladium systems, all proposed mechanisms account for an alkynyl/alkyne intermediate with cis addition of the alkynyl C-Pd bond to the alkyne in a Markovnikov fashion, in which the palladium is placed at the less-substituted carbon, both to minimize steric hindrance and to provide the most stable C-Pd bond (Scheme 2a). The reverse regioselectivity in the palladium-catalyzed dimerization of aryl acetylenes has been attributed to an agostic interaction between the transition metal and ortho protons of the aromatic ring in the substrate (Scheme 2b) [7, 8],... 

The Pd-catalyzed hydrocarbonations of methyleneaziridines 14 do not proceed through the formation of a Jt-allylpalladium intermediates, instead via a chelation effect. The hydropalladation of methyleneaziridines with the Pd(II) hydride species 16, followed by reductive elimination gives the non-ring-opened products 15. It is noteworthy to mention that the palladium-catalyzed intermolecular or intramolecular addition of nitriles to carbon-carbon multiple bonds can be explained by the hydropalladation mechanism, except for the intramolecular addition to the C=C triple bond of alkynes (vide infra). 

Both amido and pinacol derivatives of B-Si compounds 125 and 126 added to terminal and internal alkynes in the presence of a palladium244-246 or platinum(O) catalyst247 by a mechanism involving an oxidative addition-insertion process (Equation (39)).248 On the other hand, phosphine-free nickel(O) catalyst resulted in the dimerization of alkynes giving a Z,Z-isomer of l-silyl-4-borylbutadiene derivatives.249 Since the palladium-catalyzed cross-coupling at the C-B bond is faster than the G-Si bond of 137, a silylboration-cross-coupling sequence provided a method for the synthesis of 1-alkenylsilanes.246... 

The insertion of CO into palladium carbon bonds is a common step in many palladium-catalyzed carbonylation reactions and polymerizations. This reaction takes place under moderate CO pressure (1-3 atm). From the range of compounds that can be carbonylated, it can be inferred that CO will insert into alkyl, aryl, and alkynic bonds (equation 13). One of the few types of Pd-C bonds inert to CO insertion is the Pd-acyl bond, thus only single carbonylations are normally observed. However, a few examples of double carbonylation have been reported. In the case of palladium-catalyzed formation of PhCOCONEt2 from Phi, CO, and NHEt2, reductive elimination from a bisacyl complex has been established as the mechanism, rather than CO insertion into a Pd-acyl bond. 

Trost and co-workers have made great strides in developing the palladium-catalyzed cycloisomerization of enynes into a powerful ring-forming method [39]. In most cases, the intimate details of these reactions are unknown. They are considered here, since a Heck cyclization is a potential step of one possible mechanistic sequence [40]. Two plausible mechanisms for palladium-catalyzed cycloisomerization of enynes are depicted in Scheme 6-17. In the Heck pathway (101 102 103104), hydropalladation of the alkyne is... 

Bohm, V. P. W., Herrmann, W. A. Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions, 13 a copper-free procedure for the palladium-catalyzed Sonogashira reaction of aryl bromides with terminal alkynes at room temperature. Eur. J. Org. Chem. 2000,3679-3681. 

Scheme 5.7.18 Proposed mechanism of the palladium-catalyzed dimerization-carbostannylation of alkynes...

The reaction of an alkene (or alkyne), CO, and H2O to directly produce a carboxylic acid is called Reppe carbony-lation chemistry or, more recently, hydrocarboxylation see Reppe Reaction). An excellent review of palladium-catalyzed Reppe carbonylation systems has been published recently by Kiss, and coverage of this important material will not be repeated here. This catalytic reaction has been known for quite some time, although the stoichiometric Ni(CO)4-based carbonylation of acetylene was the first commercial carbonylation process implemented (equation 13). The extreme toxicity of Ni(CO)4, however, has limited practical applications see Nickel Organometallic Chemistr. Co, Rh, and Pd catalysts have certainly replaced Ni(CO)4 in smaller-scale laboratory reactions, though for historical reasons a number of the fundamental mechanisms discussed in this section are based on Ni(CO)4. 

For the palladium-catalyzed cyclotrimerization of arynes, a mechanism similar to the accepted mechanism for [2+2+2] cycloaddition of alkynes may be proposed (Scheme 15). Though it has not been studied in depth, some experimental results support it. Firstly, aryne-forming conditions are necessary for the reaction to proceed (see Table 1, entry 8) no reaction of trifiate 55 takes place at room temperature in the presence of the catalyst if fluoride is absent, which rules out a mechanism initiated by the oxidative addition of the aryl trifiate to palladium. Data obtained in the closely related cocycloadditions of benzyne with alkynes, discussed below, hkewise point to benzyne as the reactive species. Secondly, the benzyne-palladium complex 67 is a plausible initial intermediate because the ability of group 10 metals to coordinate benzyne is well known (see Sect. 1.2.2), and although benzyne complexes of palladium have eluded isolation (apparently because of their instability) [7,26], they may well be able to exist as transient intermediates in a catalytic cycle such as that shown in Scheme 15. Thirdly, it is known that benzyne complex 34 can form metallacy-cles similar to 68, albeit with dcpe as hgand instead of PPhj [26]. 

Internal alkynes will also readily undergo palladium-catalyzed annulation by functionally substituted aromatic or vinylic halides to afford a wide range of heterocycles and carbocycles. However, the mechanism here appears to be quite different from the mechanism for the annulation of terminal alkynes. In this case, it appears that the reaction usually involves (1) oxidative addition of the organic halide to Pd(0) to produce an organopalladium(II) intermediate, (2) subsequent insertion of the alkyne to produce a vinylic palladium intermediate, (3) cyclization to afford a palladacycle, and (4) reductive elimination to produce the cyclic product and regenerate the Pd(0) catalyst (Eq. 28). 

The scope and mechanism of palladium-catalyzed annulation of internal alkynes to give 2,3-disubstituted indoles, the effect of substituents on the aniline nitrogen or on the alkynes, as well as the effect of the salts such as LiCl or n-BuaNCl were studied by Larock and coworkers (1998 JOC7652). The mechanism they propose for indole synthesis proceeds as follows (a) reduction of the Pd(OAc)2 to Pd(0) (b) coordination of the chloride to form a chloride-Ugated zerovalent palladium species (c) oxidative addition of the aryl iodide to Pd(0) (d) coordination of the alkyne to the... 

Palladium-catalyzed reactions can be used to connect the terminal end of an alkyne and aromatic iodide, as shown in the reaction below. They are useful in industry and are widely employed in the academic arena. The experiment presented here was adapted from an article by Goodwin, Hurst, and Ross. The mechanism shown is for the coupling of l-iodo-4-nitrobenzene with 1-pentyne. Small amounts of a dimer obtained from the coupling of the 1-alkynes are also formed in these... 

Palladium-catalyzed alkynylation is an important method for the synthesis of alkynes [44]. Comasseto et al. described the efficient coupling of vinylic tellurides with alkynes using PdCl2/CuCl2 as the catalytic system to afford enyne derivatives. In order to further understand the mechanism of this reaction, a study using the ESI-MS/MS technique was performed by the authors [45]. The particular reaction studied by mass spectrometry is shown in Scheme 7.24. The coupling retains the doublebond geometry. 

In 2013, Takemoto and co-workers developed a palladium-catalyzed isocyanide insertion and alkyne functionalization for the synthesis of 2-arylindole derivatives, including tetracyclic carbazoles (Scheme 2.105). In this process, the formation of two C-C bonds via isocyanide insertion was achieved, and isocyanide was effectively used by incorporating both the C and N atoms as components of the indole skeleton. Regarding the reaction mechanism, the reaction started with the oxidative addition of Pd(0) to aryl... 

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