Intermolecular reactions catalyst

The rhodium-catalyzed tandem carbonyl ylide formation/l,3-dipolar cycloaddition is an exciting new area that has evolved during the past 3 years and high se-lectivities of >90% ee was obtained for both intra- and intermolecular reactions with low loadings of the chiral catalyst. 

Acyclic diene molecules are capable of undergoing intramolecular and intermolec-ular reactions in the presence of certain transition metal catalysts molybdenum alkylidene and ruthenium carbene complexes, for example [50, 51]. The intramolecular reaction, called ring-closing olefin metathesis (RCM), affords cyclic compounds, while the intermolecular reaction, called acyclic diene metathesis (ADMET) polymerization, provides oligomers and polymers. Alteration of the dilution of the reaction mixture can to some extent control the intrinsic competition between RCM and ADMET. 

This behaviour was rationalised by a stepwise reduction mechanism, in which a high catalyst or KOH concentration gives a high hydride concentration and leads to the aniline formation and suppression of intermolecular reactions to the dimeric azo-compound. 

Rh2(OAc)4 has become the catalyst of choice for insertion of carbene moieties into the N—H bond of (3-lactams. Two cases of intermolecular reaction have been reported. The carbene unit derived from alkyl aryldiazoacetates 322 seems to be inserted only into the ring N—H bond of 323 246). Similarly, N-malonyl- 3-lactams 327 are available from diazomalonic esters 325 and (3-lactams 326 297). If, however, the acetate function in 326 is replaced by an alkylthio or arylthio group, C/S insertion rather than N/H insertion takes place (see Sect. 7.2). Reaction of ethyl diazoacetoacetate 57b with 328 also yields an N/H insertion product (329) 298>, rather than ethyl l-aza-4-oxa-3-methyl-7-oxabicyclo[3.2.0]hex-2-ene-2-earboxylate, as had been claimed before 299). 

Du Bois originally used rhodium(n) acetate and rhodium triphenylacetate (tpa) as catalysts and found that regio-and diastereocontrol was influenced by the catalysts, but neither was particularly effective when low catalyst loadings were used. Inspired by the bridged dirhodium catalysts which have been developed for carbenoid chemistry,40,273,274 a second generation catalyst Rh2(esp)2 116 (esp = a,a,a, o -tetramethyl-l,3-benzenedipropionate) was designed which was capable of much higher turnover numbers (Scheme ll).275 Furthermore, this catalyst was effective in intermolecular reactions. 

The intermolecular reaction of phenols with propiolic esters occurs in the presence of a Pd(OAc)2 catalyst to afford coumarin derivatives directly.48,48a An exclusive formation of 5,6,7-trimethoxy-4-phenylcoumarin is observed in the Pd(OAc)2-catalyzed reaction of 3,4,5-trimethoxyphenol with ethyl phenylpropiolate in TFA (Equation (46)). Coumarin derivatives are obtained in high yields in the cases of electron-rich phenols, such as 3,4-methylenedioxyphenol, 3-methoxyphenol, 2-naphthol, and 3,5-dimethylphenol. A similar direct route to coumarin derivatives is accomplished by the reaction of phenols with propiolic acids (Equation (47)).49 A similar reaction proceeds in formic acid at room temperature for the synthesis of coumarins.50,50a Interestingly, Pd(0), rather than Pd(n), is involved in this reaction. 

Chiral dirhodium(II) catalysts with carboxylate or carboxamidate ligands have recently been developed to take advantage of their versatility in metal carbene transformation, and these have now become the catalysts of choice for cyclopropanation. Chiral carboxylate ligands 195,103 196,104 and 197105 have been used for tetrasubstitution around a dirhodium(II) core. However, the enantioselectivity in intermolecular reactions with simple ketenes is marginal. 

Concept Most of the synthetic asymmetric catalysts show limited activity in terms of either enantioselec-tivity or chemical yields. The major difference between synthetic asymmetric catalysts and enzymes is that the former activate only one side of the substrate in an intermolecular reaction, whereas the latter can not... 

The development of catalytic asymmetric reactions is one of the major areas of research in the field of organic chemistry. So far, a number of chiral catalysts have been reported, and some of them have exhibited a much higher catalytic efficiency than enzymes, which are natural catalysts.111 Most of the synthetic asymmetric catalysts, however, show limited activity in terms of either enantioselectivity or chemical yields. The major difference between synthetic asymmetric catalysts and enzymes is that the former activate only one side of the substrate in an intermolecular reaction, whereas the latter can not only activate both sides of the substrate but can also control the orientation of the substrate. If this kind of synergistic cooperation can be realized in synthetic asymmetric catalysis, the concept will open up a new field in asymmetric synthesis, and a wide range of applications may well ensure. In this review we would like to discuss two types of asymmetric two-center catalysis promoted by complexes showing Lewis acidity and Bronsted basicity and/or Lewis acidity and Lewis basicity.121... 

A development of the last two decades is the use of Wacker activation for intramolecular attack of nucleophiles to alkenes in the synthesis of organic molecules [9], In most examples, the nucleophilic attack is intramolecular, as the rates of intermolecular reactions are very low. The reaction has been applied in a large variety of organic syntheses and is usually referred to as Wacker (type) activation of alkene (or alkynes). If oxygen is the nucleophile, it is called oxypalladation [10], Figure 15.4 shows an example. During these reactions the palladium catalyst is often also a good isomerisation catalyst, which leads to the formation of several isomers. 

Two precedent examples had been reported of the enantioselective [2+2+2] cycloaddition of alkynes. In one case, an enantioposition-selective intermolecular reaction of a triyne with acetylene generated an asymmetric carbon at the benzylic position of a formed benzene ring [19]. In the other case, an intramolecular reaction of a triyne induced helical chirality [20]. Both reactions were developed by chiral Ni catalysts. 

In the intermolecular reaction of tetraynes, where two 1,6-diyne moieties were directly connected, with monoalkynes, CHIRAPHOS (2,3-bis(diphenylphosphino) butane) was the choice of chiral ligand, and axial chirality was enantiomericaUy generated between the formed benzene rings (Scheme 11.17). Hexaynes with a 1,3-diyne moiety also underwent an intramolecular [2-i-2-i-2] cycloaddition, and the Ir-xylylBINAP (2,2 -bis[di(3,5-xylyl)phosphino]-l,l -binaphthyl) catalyst induced an excellent enantiomeric excess (ee) (Scheme 11.18) [24]. 

The intermolecular carbocyclization with a strained olefin, such as norbornene 35, has been frequently used for proof-of-prindple in challenging metal-catalyzed transformations. The use of rhodium catalysts fadhtates the intermolecular reaction, albeit in modest yield and with poor regioselectivity (Scheme 11.10). Ethylene 39 can also be utilized to this end, but generally affords the carbocydization products in low yield, as... 

Isoquinoline Reissert compounds of type 12 could be easily converted to the corresponding 1-cyanoisoquinolines (13) by simple base treatment (4,5) (Scheme 3). This transformation also takes place with high yields when type 12 compounds are oxidized with molecular oxygen in a two-phase system in the presence of phase-transfer catalysts (12-14). It should be mentioned that similar oxidation of dihydro Reissert compounds of type 14 afforded the corresponding dihydroisocarbostyril derivatives (15) (12-14). Base treatment of isoquinoline Reissert eompounds followed by intramolecular rearrangement, due to the absence of a proper intermolecular reaction partner, results in 1-acylisoquinoline derivatives (18) (3). 

The use of mediators to improve reactivity or selectivity in nitrone cycloaddition chemistry begins with the nitrone generation step. As is well known, the N-alkyla-tion of oximes provides one of the most direct and convenient synthetic routes to N-alkylated nitrones from readily available aldehydes and ketones. Electrophilic mediators have been employed to activate alkenes for N-alkylation, both in intramolecular and intermolecular reactions. They include activation of the internal alkene function by the action of (a) strong nonmetallic electrophiles such as phenyl-selenenyl sulfate (159), and (b) metallic catalysts such as Ag(I) (160) and Pd(II) ions... 

As olefin CM is a thermodynamically controlled intermolecular reaction, there are several inherent challenges toward achieving product selectivity. First and foremost, if a catalyst cannot distinguish between the two olefin crosspartners, a statistical mixture of products will result (Scheme 2). In this situation, one of the olefin cross-partners would need to be added to the reaction in excess to achieve a synthetically useful yield (e.g., 10 equiv. required to attain a 91% yield). 

Following the success with cobalt and rhodium, Shibata reported Ir(i)-based enantioselective catalytic reaction. Right after their observation that the efficiency of [IrCl(COD)]2-catalyzed PKR substantially increased by addition of a phosphane co-ligand, they moved directly to use chiral phosphanes and examined the enantioselectivity. " TON and TOE of the reaction were low and the number of examples was limited. Typically, the reaction required a fair amount of Ir(i) catalyst [IrCl(COD)]2 (0.1-0.15 equiv.) and (reaction time. However, this has remained as the best in terms of enantioselectivity to date. Moreover, this catalytic system provided the first asymmetric intermolecular reaction as well. 

The rates to methanol and ethylene glycol have qualitatively similar dependences on pressure (Fig. 18) and promoter concentration (Fig. 20), but somewhat different dependences on catalyst concentration (Fig. 19). The latter study shows that the ethylene glycol-producing reaction is more highly dependent than the methanol-forming reaction on processes intermolecular in catalyst components. There appears to be no evidence that all of the methanol and ethylene glycol are formed from a common precursor. Indeed, since methanol is known to be produced by unpromoted ruthenium catalysts, this product could be formed by several independent pathways in the promoted system. 

Solvent-free conditions were used by Tanaka et al. in their assays to obtain intermolecular reactions from alkynes and anilines. The chosen catalyst was [AuMe(PPh3)] with an acidic promoter [92]. Reaction, whose effectiveness was greater in the case of aromatic amines, proceeded via Markovnikov by amine electrophilic attack of the alkyne in a similar way to the methanol addition proposed by Teles (see Section 2.1.3.2) and provided high yields and TONs. 

Since the dinuclear catalysts transform the intermolecular reaction of ethoxide with substrate into an intramolecular reaction within a supramolecular complex (Scheme 5.3), the effective molarity (EM) parameter, defined as kintra/fcinten strictly applies to the catalytic process at hand and, more in general, to processes in which molecular receptors promote the reaction of two simultaneously complexed reactants [35]. 

Surface effects and adsorption equilibria thus will significantly influence the course of photoelectrochemical transformations since they will effectively control the movement of reagents from the electrolyte to the photoactivated surface as well as the desorption of products (avoiding overreaction or complete mineralization). The stability and accessibility toward intermolecular reaction of photogenerated intermediates will also be controlled by the photocatalyst surface. Since diffusion and mass transfer to and from the photocatalyst surface will also depend on the solvent and catalyst pretreatment, detailed quantitative descriptions will be difficult to transfer from one experiment to another, although qualitative principles governing these events can be easily recognized. 

Carbenoids derived from the metal catalysed decomposition of diazo compounds undergo various chemical transformations. Control of chemoselectivity by choice of the appropriate catalyst has significantly increased the synthetic viability of catalytic cyclopropanation reactions. Intermolecular reaction of unsaturated alcohols with carbenoids derived from catalytic decomposition of alkyl diazoesters has been reported by Noels and... 

Secondly, the product distribution for the reaction of 3-phenylpropanoyl chloride with anisole catalyzed by zeolite beta (Table 4) is very similar to that found for acid faujasites and quite different to the AICI3 catalysis in which the ratio of 3 to 4 obtained is 7.0. Taking into account the adsorption properties of zeolites, their enhancement of the intermolecular reaction could be attributed to a high concentration of both reagents inside the cavities, thus promoting more efficiently the formation of the propiophenone 4 than a conventional AICI3 catalyst. 

Although C—H insertion reactions rarely occur in intermolecular reactions with diazoacetates, these are common side reactions with diazomalonates3132 (equation 10) and diazo ketones (with a-allyl vinyl ethers).33 Several mechanistic pathways are available to generate the products of an apparent direct C—H insertion reaction and these include dipolar intermediates, ir-allyl complexes and ring opening of cyclopropanes.1 Oxidative problems due to the presence of oxygen are common with copper catalysts, but these are rarely encountered with rhodium catalysts except in systems where the carbenoid is ineffectively captured.34... 

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. 

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