Palladium catalysts cycloaddition reactions

While simple unactivated cyclopropanes have yet to be used for [3 + 2] cycloaddition, Tsuji and coworkers have developed a palladium-catalyzed cycloaddition reaction using electron-deficient vinylcy-clopropanes. Thus, vinylcyclopropane (43) undergoes smooth cyclization with methyl acrylate in the presence of a palladium catalyst to give vinylcyclopentane (44) as a mixture of diasteroisomers (equation 35). The cycloaddition probably proceeds through the zwitterionic ( ir-allyl)palladium intermediate (45) and its stepwise reaction with the acrylate (equation 36). Enones such as cyclopentenone and methyl vinyl ketone will also react. Reaction of the same vinylcyclopropane with phenyl isocyanate produces vi-nyllactam (46) (equation 37).Some cycloaddition reactions with (cyclopropyl)Fp complexes have also been reported. However, the substrates are limited to SO2 and TCNE and the yields have not been disclosed (equation 38). ... 

Intramolecular cycloadditions of substrates with a cleavable tether have also been realized. Thus esters (37a-37d) provided the structurally interesting tricyclic lactones (38-43). It is interesting to note that the cyclododecenyl system (w = 7) proceeded at room temperature whereas all others required refluxing dioxane. In each case, the stereoselectivity with respect to the tether was excellent. As expected, the cyclohexenyl (n=l) and cycloheptenyl (n = 2) gave the syn adducts (38) and (39) almost exclusively. On the other hand, the cyclooctenyl (n = 3) and cyclododecenyl (n = 7) systems favored the anti adducts (41) and (42) instead. The formation of the endocyclic isomer (39, n=l) in the cyclohexenyl case can be explained by the isomerization of the initial adduct (44), which can not cyclize due to ring-strain, to the other 7t-allyl-Pd intermediate (45) which then ring-closes to (39) (Scheme 2.13) [20]. While the yields may not be spectacular, it is still remarkable that these reactions proceeded as well as they did since the substrates do contain another allylic ester moiety which is known to undergo ionization in the presence of the same palladium catalyst. 

For the activation of a substrate such as 19a via coordination of the two carbonyl oxygen atoms to the metal, one should expect that a hard Lewis acid would be more suitable, since the carbonyl oxygens are hard Lewis bases. Nevertheless, Fu-rukawa et al. succeeded in applying the relative soft metal palladium as catalyst for the 1,3-dipolar cycloaddition reaction between 1 and 19a (Scheme 6.36) [79, 80]. They applied the dicationic Pd-BINAP 54 as the catalyst, and whereas this type of catalytic reactions is often carried out at rt or at 0°C, the reactions catalyzed by 54 required heating at 40 °C in order to proceed. In most cases mixtures of endo-21 and exo-21 were obtained, however, high enantioselectivity of up to 93% were obtained for reactions of some derivatives of 1. 

The reactions of nitrones constitute the absolute majority of metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions. Boron, aluminum, titanium, copper and palladium catalysts have been tested for the inverse electron-demand 1,3-dipolar cycloaddition reaction of nitrones with electron-rich alkenes. Fair enantioselectivities of up to 79% ee were obtained with oxazaborolidinone catalysts. However, the AlMe-3,3 -Ar-BINOL complexes proved to be superior for reactions of both acyclic and cyclic nitrones and more than >99% ee was obtained in some reactions. The Cu(OTf)2-BOX catalyst was efficient for reactions of the glyoxylate-derived nitrones with vinyl ethers and enantioselectivities of up to 93% ee were obtained. 

The NHCs have been used as ligands of different metal catalysts (i.e. copper, nickel, gold, cobalt, palladium, rhodium) in a wide range of cycloaddition reactions such as [4-1-2] (see Section 5.6), [3h-2], [2h-2h-2] and others. These NHC-metal catalysts have allowed reactions to occur at lower temperature and pressure. Furthermore, some NHC-TM catalysts even promote previously unknown reactions. One of the most popular reactions to generate 1,2,3-triazoles is the 1,3-dipolar Huisgen cycloaddition (reaction between azides and alkynes) [8]. Lately, this [3h-2] cycloaddition reaction has been aided by different [Cu(NHC)JX complexes [9]. The reactions between electron-rich, electron-poor and/or hindered alkynes 16 and azides 17 in the presence of low NHC-copper 18-20 loadings (in some cases even ppm amounts were used) afforded the 1,2,3-triazoles 21 regioselectively (Scheme 5.5 Table 5.2). 

In the presence of nickel(0), tethered diene-VCPs react to produce eight- and five-membered ring products (Scheme 2). Palladium(O) and cobalt(m) were also tried but produced only decomposition products. However, in the presence of Wilkinson s catalyst (RhCl(PPh3)3), tethered diene-VCP 1 was cleanly converted to triene 4 in 91% yield. Although the desired cycloaddition reaction was not obtained, the cleavage of the cyclopropane ring was encouraging.22... 

Furukawa and co-workers (368,369) succeeded in applying the softer dicationic Pd-BINAP 260 as a catalyst for the 1,3-dipolar cycloaddition between 225 and 241a (Scheme 12.82). In most cases, mixtures of endo-243 and exo-243 were obtained, however, enantioselectives of up to 93% ee were observed for reactions of some derivatives of 225. A transition state structure has been proposed to account for the high selectivities obtained for some of the substrates (368). In the structure shown in Scheme 12.82, the two phosphorous atoms of the Tol-BINAP ligand and the two carbonyl oxygens of the crotonoyl oxazolidinone are arranged in a square-planar fashion around the palladium center. This leaves the ii-face of the alkene available for the cycloaddition reaction, while the re-face is shielded by one of the Tol-BINAP tolyl groups. 

Methylidenecyclopropanes were converted in a formal [3+2] cycloaddition both to fiirane and pyrrole derivatives. Their reaction, in the presence of a suitable palladium catalyst, with a carbonyl group led to the construction of a tetrahydrofiirane ring (3.92.),117 The analogous reaction in... 

Distal ring-opening is also observed in the intramolecular 3+2 cycloaddition reaction of a 3-pentenone diphenylmethylenecyclopropane derivative in the presence of bis(diben-zylideneacetone)palladium/tri-isopropyl phosphite catalyst, affording regioselectively a diphenylmethylene pentalenone system (equation 360)424. Similarly, thermal cyclization of... 

The reaction of methylenecyclopropanes with transition metal complexes is well known to promote a catalytic a-ir cycloaddition reaction with unsaturated compounds, in which a trimethylenemethane complex might exist71-76. Recently, much interest has been focused on the interaction of strained silicon-carbon bonds with transition metal complexes. In particular, the reaction of siliranes with acetylene in the presence of transition metal catalysts was extensively investigated by Seyferth s and Ishikawa s groups77-79. In the course of our studies on alkylidenesilirane, we found that palladium catalyzed reaction of Z-79 and E-79 with unsaturated compounds displayed ring expansion reaction modes that depend on the (Z) and (E) regiochemistry of 79 as well as the... 

Various methods have been explored for the synthesis of lactones by cycloaddition reactions. The most common of these types of reaction is the [2+2] cycloaddition of aldehydes and ketene. Palladium(ll) complexes, [Pd(dppb)2(PhCN)2](BF4)2, have been shown to be efficient catalysts for this reaction (Equation 34) <2000CC73>. 

The palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a [42] and aziridine 20b [39] with the activated olefin 4a for the formation of five membered cyclic ether 21a and pyrrolidine derivative 21b has also been reported in our laboratories. The mechanistic issue is very much similar to that discussed in Scheme 9. Pd(0) catalyst added oxidatively to 20 to produce the 7r-allylpalladium complex 22. The Michael addition of a hetero nucleophile in 22 to the activated olefin 4a gives 23 which undergoes intramolecular nucleophilic attack on the inner 7r-allylic carbon atom to give the cy-clized products 21 and Pd(0) species is generated (Scheme 10). Similarly, the palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a with the N-losylimincs 24 is also known (Scheme 11) [43]. Intermolecular cycloaddition of vinyl epoxides and aziridines with the heterocumulenes such as isocyanates, carbodiimides and isothiocyanates is also known [44,45]. Alper et al. reported the regio- and enatioselective formation of the thiaolidine, oxathiolane, and dithiolane derivatives by the palladium-catalyzed cyclization reaction of 2-vinylthiirane with heterocumulenes [46]. 

Ionic liquids can be used as replacements for many volatile conventional solvents in chemical processes see Table A-14 in the Appendix. Because of their extraordinary properties, room temperature ionic liquids have already found application as solvents for many synthetic and catalytic reactions, for example nucleophilic substitution reactions [899], Diels-Alder cycloaddition reactions [900, 901], Friedel-Crafts alkylation and acylation reactions [902, 903], as well as palladium-catalyzed Heck vinylations of haloarenes [904]. They are also solvents of choice for homogeneous transition metal complex catalyzed hydrogenation, isomerization, and hydroformylation [905], as well as dimerization and oligomerization reactions of alkenes [906, 907]. The ions of liquid salts are often poorly coordinating, which prevents deactivation of the catalysts. 

As an approach to the synthesis of piperidines with stereocontrol, multiple functionality, and flexibility, the authors employed a [3+3] cycloaddition reaction of a silylpropenyl acetate with aziridines in the presence of a palladium catalyst. The key intermediate is a palladium-trimethylenemethane (Pd-TMM) complex <03JOC4286>. Optically active aziridines gave enantiomerically pure piperidines. 

Synthesis of 1,3-oxazolidines 285 has been described by a palladium-catalyzed cycloaddition of vinylic oxiranes 284 with Af-tosyl imines 283 (Scheme 81) <2000H(52)885>. This reaction proceeded with high yields and good regioisomeric selectivity and the palladium catalyst of choice was a 1 2 Pd(dba)2 DPPE complex. 

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