Intramolecular reactions catalyst systems

A new process developed by Institut Francais du Petrole produces butene-1 (1-butene) by dimerizing ethylene.A homogeneous catalyst system based on a titanium complex is used. The reaction is a concerted coupling of two molecules on a titanium atom, affording a titanium (IV) cyclic compound, which then decomposes to butene-1 by an intramolecular (3-hydrogen transfer reaction. ... 

Trost and others have extensively studied the ruthenium-catalyzed intermolecular Alder-ene reaction (see Section 10.12.3) however, conditions developed for the intermolecular coupling of alkenes and alkynes failed to lead to intramolecular cycloisomerization due the sensitivity of the [CpRu(cod)Cl] catalyst system to substitution patterns on the alkene.51 Trost and Toste instead found success using cationic [CpRu(MeCN)3]PF6 41. In contrast to the analogous palladium conditions, this catalyst gives exclusively 1,4-diene cycloisomerization products. The absence of 1,3-dienes supports the suggestion that the ruthenium-catalyzed cycloisomerization of enynes proceeds through a ruthenacycle intermediate (Scheme 11). 

Commensurately with the development of various catalyst systems, the Pd-catalyzed G-O cross-coupling has found a number of synthetic applications. Examples include the syntheses of the protein kinase G (PKC) activator (+)-decursin,104 the natural product heliannuol E,105 a chiral 2-methyl chroman,106 and a series of aryloxy and alkoxy porphyrins.107 The Buchwald-Hartwig coupling has also been utilized in the preparation of a heterocycle library.108 Intramolecular O-arylation has also been achieved in the reactions of enolates with aryl halides leading to benzofur-ans.109,110 Finally, a double cross-coupling between an 0-dibromobenzene and a glycol has also been applied for the preparation of benzodioxanes (Equation (16)).1... 

The ruthenium catalyst system, 14, shown in Fig. 3, also carries out ADMET condensation chemistry, albeit with higher concentrations being required to achieve reasonable reaction rates [32]. The possibility of intramolecular compl-exation with this catalyst influences the polymerization reaction, but nonetheless, ruthenium catalysis has proved to be a valuable contributor to overall condensation metathesis chemistry. Equally significant, these catalysts are tolerant to the presence of alcohol functionality [33] and are relatively easy to synthesize. For these reasons, ruthenium catalysis continues to be important in both ADMET and ring closing metathesis chemistry. 

In Grigg s approach to hippadine (37), he established the connection between the two phenyl rings via the Stille-Kelly reaction [45]. When diiodide 35 was submitted to the Pd(0)/ditin catalyst system, the intramolecular cyclization was realized to establish the C—C bond in lactam 36. Oxidation of the indoline moiety in 36 using 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) then delivered hippadine (37). Analogously, the intramolecular Stille coupling of dibromide 38 led directly to hippadine (37) [46]. 

The reactivity of compound 113 toward reactive linear and cyclic dienophiles was reported in a study directed to find a model systems for the proposed [4+2] cycloaddition in the biosynthesis of the natural products brevianamides, paraherquamides, and marcfortines. With DMAD and diethyl azodicarboxylate the formation of 114 and 115 was almost quantitative after 48 h at 80 °C (Cbz = Carbobenzyloxygroup). When relatively unreactive dienophiles such as cyclopentene and cyclohexene were used, harsh reaction conditions and/or a Lewis acid catalyst are necessary for the formation of 116a and 116b (Scheme 16). In contrast, the analogous intramolecular reaction carried out on compound 117 takes place within a few hours at room temperature, even in the absence of a Lewis acid catalyst, to give 118 in 42% yield (Scheme 16) <2000T6345>. 

Intramolecular versions of the Morita-Baylis-Hillman reaction have also met with success using a dual Lewis acid/Lewis base catalyst system. Miller has shown that a combination of A-methyl imidazole (132) (10 mol%) and... 

Based on the precedent of Van Leeuwen and Roobeek, livinghouse and co-workers screened a variety of electron-deficient phosphine/phosphite ligands for the rhodium-catalyzed [4-1-2] reaction, which provided an alternative catalyst system for the formation of 5,6- and 6,6-ring systems [13]. The most notable of these was the tris-(hexafluoro-2-propyl) phosphite-modified rhodium complex, which was applicable to both carbon- and oxygen-tethered substrates, and also provided the first example of a facial-directed diastereoselective intramolecular rhodium-catalyzed [4-i-2] reaction (Eq. 4). 

This catalyst system was the first to utilize both terminal alkynes and olefins in the intramolecular reaction. Although a mechanistic rationale for the observed stereoselectivity was not offered, the formation of the single stereoisomer 26 may be rationalized through the diastereotopic binding of the rhodium complex to the diene moiety (Scheme 12.3). This facial selective binding of the initial ene-diene would then lead to the formation the metallacycle III, which ultimately isomerizes and reductively eliminates to afford the product [14]. 

The proposed mechanism is given in Scheme 15. Initially the dissociation of water, maybe trapped by the molecular sieve, initiates the catalytic cycle. The substrate binds to the palladium followed by intramolecular deprotonation of the alcohol. The alkoxide then reacts by /i-hydride elimination and sets the carbonyl product free. Reductive elimination of HOAc from the hydride species followed by reoxidation of the intermediate with dioxygen reforms the catalytically active species. The structure of 13 could be confirmed by a solid-state structure [90]. A similar system was used in the cyclization reaction of suitable phenols to dihydrobenzofuranes [92]. The mechanism of the aerobic alcohol oxidation with palladium catalyst systems was also studied theoretically [93-96]. 

Members of the tetracyclic dibenzopyrrocoline alkaloid family can be prepared by the intramolecular ring closure of l-(o-halobcnzyl)-tetrahydroisoquinoline derivatives. (3.38.)47 The analogous transformation of dihydroisoquinolines (3.39.) proceeds probably through the isomeric enamine form obtained by the tautomeric shift of the double bond 48 The palladium-carbene catalyst system applied in these reactions was also effective in the preparation of indoline, indolizidine and pyrrolizidine derivatives 49... 

Some gold catalyst species proved to be better than platinum in the intramolecular reactions of unactivated alkenes, as studied by Widenhoefer et al. [61-63]. Gold was allowed to work under mild conditions and the scope of the reaction was also broader than with other late-transition-metal catalyst systems, leading to the formation of five-and six-membered rings. 

Krause and Belting studied a tandem catalyzed reaction, in this case intramolecular cyclization and intermolecular hydroalkoxylation. The substrates were various homo-propargylic alcohols in the presence of non-tertiary alcohols and a dual catalyst system consisting of Br( >nsted acids and a gold precatalyst (Equation 8.43). 

Ruhland et al. used PdCl2(dppf)-NEt3 Heck conditions to add to a resin-bound aryl iodide, thereby generating supported 4-styryl (3-lactams, as shown in Scheme 17.45 This catalyst system, also found to be effective for the Suzuki reaction (see Section 2.4), is unusual for the Heck reaction and had only previously been used for an intramolecular cyclization.46 The more usual conditions of Pd(OAc)2/phosphine/NEt3 or K2C03 were found to be ineffective. 

The inclusion of a separate chapter on catalysed cyclopropanation in this latest volume of the series is indicative of the very high level of activity in the area of metal catalysed reactions of diazo compounds. Excellent, reproducible catalytic systems, based mainly on rhodium, copper or palladium, are now readily available for cyclopropanation of a wide variety of alkenes. Both intermolecular and intramolecular reactions have been explored extensively in the synthesis of novel cyclopropanes including natural products. Major advances have been made in both regiocontrol and stereocontrol, the latter leading to the growing use of chiral catalysts for producing enantiopure cyclopropane derivatives. 

The intramolecular reaction between diazo ketones and benzenes is an effective way to generate a range of bicyclic systems.7 The earlier copper-based catalysts have largely been superseded by rho-dium(ll) salts. Unlike the case in the intermolecular reactions, rhodium(ll) acetate is the catalyst that has been most commonly used. Studies by McKervey,133 136 however, indicated that rhodium(II) mandelate, which would be expected to generate a slightly more electrophilic carbenoid than rhodium(ll) acetate, often gave improved yields. 

The direct alkenylation of arylamines at the ortho position has been reported in reactions of o -chloroalkenylmagnesium chloride with N-lithioarylamines.22 Use of the CuI-L-proline catalyst system in DMSO has been found to be successful in promoting reactions of aryl iodides and bromides with activated methylene compounds, such as ethyl acetoacetate and diethyl malonate.23 The same catalyst in dioxane has been used in intramolecular cyclization of ene-carbamates leading to indoles or pyrrolo[2,3-cjpyridines.24... 

Asymmetric intramolecular Diels-Alder reaction.1 This chiral Ti catalyst system 4 is also effective for enantioselective intramolecular Diels-Alder reactions (equation I). In this particular case, a dithiane group accelerates the rate and enhances the em/o-selectivity, and is comparable to the gem-dialkyl effect. 

The Sn(Oct)2 catalyst is generally active at elevated temperatures, leading to some intermolecular and intramolecular transesterification reaction [140]. Recently, a new catalyst system for the ROP of lactones has been reported, based on tin(II) or scandium(III) trifluoromethanesulfonate [141,142]. These catalysts are very versatile, and highly selective, and they can be used under mild conditions. 

The aziridination of olefins, which forms a three-membered nitrogen heterocycle, is one important nitrene transfer reaction. Aziridination shows an advantage over the more classic olefin hydroamination reaction in some syntheses because the three-membered ring that is formed can be further modified. More recently, intramolecular amidation and intermolecular amination of C-H bonds into new C-N bonds has been developed with various metal catalysts. When compared with conventional substitution or nucleophilic addition routes, the direct formation of C-N bonds from C-H bonds reduces the number of synthetic steps and improves overall efficiency.2 After early work on iron, manganese, and copper,6 Muller, Dauban, Dodd, Du Bois, and others developed different dirhodium carboxylate catalyst systems that catalyze C-N bond formation starting from nitrene precursors,7 while Che studied a ruthenium porphyrin catalyst system extensively.8 The rhodium and ruthenium systems are... 

Table 14 shows activation parameters of the intramolecular reactions of Michaelis complexes of which the hydrolyses of ABA(7) by poly(ABI-py) and poly(ABI-am) are the same systems as shown in Table 6 (35). Both the polymers and the low molecular weight analogues have the hydrophobic binding properties. The polymer catalysts show smaller AH values by 1 3 kcal MT1 and greater AS values by 6 10 eu, than those of the small molecule catalysts.

Intramolecular olefinic C-H/olefin coupling with the aid of Ru(CO)3(PPh3)2, which is also effective for the reaction of aromatic ketones with olefins, yields the carbocyclic compounds in excellent yield (Eq. 42) [67]. This type of cy-clization reaction can be extended to an asymmetric version when the [RhCl(coe)2]2/PPFOMe catalyst system is employed [68]. 

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