Cycloaddition using palladium catalysts

The available literature data support the assertion that the outcome of the methylene cycloadditions depends to a large extent on the ability of the olefin to be coordinated to the palladium center. In that respect, the mechanism of palladium-catalyzed cyclopropanation appears to differ significantly from that of rho-dium(ll)-catalyzed cyclopropanations. One advantage of using palladium catalysts with diazomethane is associated with the possibility of synthesizing polycyclopropane adducts, a topic of current interest (vide infra) which has no general satisfactory solution with other diazo compound/catalyst combinations. This point is exemplified below for the cyclopropanation of the esters of trans-polyunsaturated acids. Moreover, the reactivity of the double bonds depends both on their position in the linear hydrocarbon chain and on their configuration (eq. (f)). 

Very recently, a different synthetic approach to fluorinated p-lactams involving catalytic hydrogenolysis of the N-O bond of isoxazohdines appeared in the literature. The method involves the synthesis of isoxazohdines (71) by 1,3-cycloaddition of aromatic nitrones to fluorinated alkenes, followed by N-O bond cleavage by hydrogenolysis using palladium catalyst (Scheme 2.34). ... 

Besides the formation of carbenes from diazo compounds and the hydroformyla-tion, rhodium (as described previously for palladium) has also been used as catalyst in domino processes involving cycloadditions. Thus, Evans and coworkers developed a new Rh(I)-catalyzed [4+2+2] cycloaddition for the synthesis of eight-membered rings as 6/2-105 using a lithium salt of N-tosylpropargylamines as 6/2-104, allyl carbonates and 1,3-butadiene (Scheme 6/2.22) [221]. The first step is an al-... 

Furukawa and co-workers (370) also used the above described palladium catalyst to the inverse electron-demand 1,3-dipolar cycloaddition of nitrones with vinyl ethers. However, all products obtained in this manner were racemic. 

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). ... 

Cyclopropenes and mcthylcnccyclopropanes serve as multifunctional reagents in transition metal catalyzed reactions22. Methylenecyclopropanes, via C-C bond cleavage, are also used as trimethylenemethane precursors in transition metal catalyzed [3 + 2] cycloadditions for selective five-membered-ring formation. Low-valent nickel and palladium complexes are used as catalysts. This method has been extensively reviewed 22 and stereoselective applications are fully described in Section D.1.6.1.2.3. 

In contrast to cyclohexenone, the unsaturated sulfoxide proved to be an excellent substrate for the [3 + 2] cycloaddition. The reaction was carried out in refluxing toluene using a catalyst derived from palladium acetate and triisopropyl phosphite, the latter acting both as a reducing agent and as a ligand. 

Dipolar cycloaddition of the diazoalkane ((CH3)2CN2) to (72) in acetone gave the tetracyclic compound (73). The unsubstituted compound did not react. The nitro group at the 6-position activates the C(5)—C(6) and C(7)—C(8) double bonds for cycloaddition <89H(28)259>. It was originally reported that [l,2,4]triazolo[4,3-a]pyridine (29) reacted with DMAD in the presence of 5% Pd/C to give (74) <81IJC(B)10>. It was subsequently shown that this reaction produces three products independent of the use of the palladium catalyst. Initial Michael addition of DMAD to (29) via its... 

D.iii. Trimethylenemethane Equivalents. Palladium catalysts can be used to convert trimethylsilyl acetate 390 to a trimethylene methane (TMM, 391) equivalent. Reaction with alkenes via [3+2]-cycloaddition (sec. 11.11) generates cyclopentanes (this process constitutes a quinane annulation reaction).229 in this reaction, the trimethylsilyl unit is a carbanion equivalent and acetate is a carbocation equivalent. In one example, Trost reacted 390 and 392 with palladium acetate and triisopropyl phosphite [P(Oi-Pr)3] to generate 393 in... 

In 1998, Guitian, Perez and co-workers reported that the cyclotrimerization of benzyne (1) to triphenylene (56) is efficiently catalyzed by palladium(O) complexes (Scheme 11) [39]. This was the first time an aryne had been the substrate in a metal-catalyzed process. The success of the reaction was based on a judicious choice of the reaction conditions, particularly with regard to the catalytic system and the method of generating the aryne. Some significant results of this seminal study are shown in Table 1. After some preliminary experiments in which nickel complexes were used as catalysts (entry 1), it was found that nucleophilic palla-dium(O) complexes efficiently promote the desired [2+2+2] cycloaddition of the strongly electrophilic substrate 1 (entries 2-6) [40]. At the same time, a systematic study of benzyne generation conditions showed that Kobayashi s method... 

Palladium catalysts have been used for cycloaddition of dimethylacetylene di-carboxylate (DMAD) to polycyclic arynes 3, 77 and 79 (Schemes 34-36). All these reactions exhibit the same reactivity pattern as is observed in the [2+2+2] cycloaddition of benzyne to DMAD (see Sect. 3.1) Pd2(dba)3 leads selectively to the cocycloaddition of one molecule of aryne and two molecules of DMAD, while Pd(PPh3)4 induces the reaction of two molecules of aryne with one molecule of DMAD. Both reactions afford the corresponding polycyclic aromatic hydrocarbons in good yields and with high chemoselectivity, constituting a novel and versatile method for the synthesis of functionalized PAHs under mild reaction conditions [70-72] (Scheme 34). 

Systems for [2 - - 3] cycloaddition can also be generated from methylene cyclopropanes (Scheme 11.43). Treatment of methylene cyclopropanes with either a nickel or a palladium catalyst in the presence of an alkene trap can lead to useful yields of the five-membered ring cycloaddition product 11.130 through oxidative... 

When malononitrile is reacted with allenes in the presence of palladium catalysts, insertion into the C-H bond is observed with formation of a linear adduct Also, phosphine catalysts are used in an asymmetric [3+2] cycloaddition of carbo-ethoxyallene 302 with enones to give the isomeric cycloadducts 303 and 304 in 54-87 % yield (% ee in 303, the major product, 87-89. ... 

The transition-metal-catalyzed [2 + 2 + 1] cycloaddition of two alkynes and heteroatom sources is a useful method for the synthesis of five-membered heterocycles. For example, a silylene species reacts with two alkynes 64 in the presence of nickel or palladium catalyst to afford substituted siloles 65 and 66. Various silylene equivalents, such as disilanes 67 [24], silacyclopropenes 68 [25], 69 [26], cyclotrisilanes 70 [27], alkylidenesilacyclopropanes 71 [28], silacyclopropanes 72, and 73 [29], have been developed as shown in Scheme 6.21. However, the utility for organic synthesis has been limited, due to the difficulty of those organosilane syntheses and the narrow alkyne scope. 

In this chapter we described [2 + 2 + 2] and related cycloaddition reactions using palladium, iron, manganese, rhenium, and other transition metals. Palladium complexes are able to catalyze [2 + 2 + 2] and related cycloaddition reactions, which proceed via cascade-type mechanism or metallacycle intermediates. It is worthy of note that arynes are suitable substrates for this palladium catalysis. Iron complexes are promising catalysts for practical [2 + 2 + 2] cycloaddition reactions, owing to their low cost and nontoxicity, although both catalytic activity and substrate scope are not satisfactory. Manganese and rhenium complexes allow the use of 3-keto esters as a cycloaddition partner. To realize the practical process and broaden the product scope, further development of new transition-metal catalysts is expected in this research field. 

Trost et al. demonstrated for several years that the trime-thylenemethane palladium complex 120 could be generated from 2-(trimethylsilyl)methyl-prop-2-en-l-yl acetate 117 with zero valent palladium catalysts and engaged in [3+2] cycloadditions.The use of this reagent was extended to [3+3] cycloadditions with aziridines in which the nitrogen is substituted with an electron-withdrawing group." ... 

Catalytic [2+2+2] cycloaddition of diyne 2.42 to allenes (Scheme 2.59, route (b) leads to cyclic condensed methylencyclohexadienes 2.169, which are often isomerized to the corresponding benzene derivatives Cycloaddition of diyne 2.42 with alkenes route (c) leads to derivatives of 1,3-cyclohexadiene 2.170, which may be used as substrates for further transformations [4]. Different transition metals M such as ruthenium, palladium, rhodium, iridium, nickel, and cobalt were used as catalysts for this reaction. 

It was shown that at room temperature in THF the macrocycle forms a stable Pd(0) complex in which three triple bonds of 2.379a are involved in complex formation [185]. Other macrocycles 2.379b-e behave similarly, and stoichiometric amounts of palladium is required to form cycloaddition products (Table 2.19, examples 2-5). The use of CpCo(CO)2 system as a catalyst at 140°C for 3.5 hours for the cyclization of 2.379b produced heterocycle 2.381b in 44% yield (entry 6, Table 2.19). With stoichiometric amounts of cobalt the yield increased to 88% (entry 7). Application of ruthenium complexes such as the Grubbs catalyst, which is also used as catalysts for the cyclotrimerization reaction of alkynes [177], in refluxing toluene, resulted in the isomerization... 

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). 

Dipolarophiles Dll. In the 1,3-dipolar cycloadditions of electron-rich olefins, such as vinyl ethers, with nitrone (585), common palladium (II) catalysts were used (Fig. 2.45). Reactions proceeded smoothly under mild conditions and in good yield, affording isoxazolidines (646) (Scheme 2.283) (799). 

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