Esters transition metal catalysts

The addition of alcohols to form the 3-alkoxypropionates is readily carried out with strongly basic catalyst (25). If the alcohol groups are different, ester interchange gives a mixture of products. Anionic polymerization to oligomeric acrylate esters can be obtained with appropriate control of reaction conditions. The 3-aIkoxypropionates can be cleaved in the presence of acid catalysts to generate acrylates (26). Development of transition-metal catalysts for carbonylation of olefins provides routes to both 3-aIkoxypropionates and 3-acryl-oxypropionates (27,28). Hence these are potential intermediates to acrylates from ethylene and carbon monoxide. 

Transesterification of methyl methacrylate with the appropriate alcohol is often the preferred method of preparing higher alkyl and functional methacrylates. The reaction is driven to completion by the use of excess methyl methacrylate and by removal of the methyl methacrylate—methanol a2eotrope. A variety of catalysts have been used, including acids and bases and transition-metal compounds such as dialkjitin oxides (57), titanium(IV) alkoxides (58), and zirconium acetoacetate (59). The use of the transition-metal catalysts allows reaction under nearly neutral conditions and is therefore more tolerant of sensitive functionality in the ester alcohol moiety. In addition, transition-metal catalysts often exhibit higher selectivities than acidic catalysts, particularly with respect to by-product ether formation. 

Migration of boron to terminal positions is observed under much milder conditions in the presence of transition metal catalysts. For example, hydroboration of 2-methyl-3-hexene by pinacolborane in the presence of Rh(PPh3)3Cl leads to the terminal boronate ester. 

The other direction concerns the use of immobilized transition metal catalysts in the synthesis of libraries of organic compounds of interest in therapeutic drug discovery. One such strategy uses immobilized catalysts (e.g., scandium complexes), leading to efficient library syntheses of quinolines, amino ketones, and amino acid esters.72,73... 

Not only heteroatom-H bonds but also activated C-H bonds can add to the jr-system of an allene. Since carbon lacks a free electron pair, the transition metal catalyst must first activate the C-H bond the new species formed will then react with the C=C double bond. For efficient activation of that kind, two acceptors (typically esters, nitriles and/or sulfones) are necessary. In accord with this mechanistic picture is the fact that the reaction does not benefit from an additional base (which would deproto-nate the pronucleophile). Hence neutral conditions are even better. 

In particular, the combined action of a transition metal catalyst and a lipase in organic solvents for the racemization and esterification steps, respectively, has been applied for the conversion of racemic secondary alcohols into their esters... 

The coupling of two molecules of aldehydes into esters (Tishchenko reaction) has been used as an efficient method for the industrial preparation of dimeric esters. Although a number of systems for such reactions using transition-metal catalysts have been reported [73], there is stiU great room for improvement of the synthetic efficiency. 

Some researchers have begun to explore the possibihty of combining transition metal catalysts with a protein to generate novel synthetic chemzymes . The transition metal can potentially provide access to novel reaction chemistry with the protein providing the asymmetric environment required for stereoselective transformations. In a recent example from Reetz s group, directed evolution techniques were used to improve the enantioselectivity of a biotinylated metal catalyst linked to streptavidin (Scheme 2.19). The Asn49Val mutant of streptavidin was shown to catalyze the enantioselective hydrogenation of a-acetamidoacrylic acid ester 46 with moderate enantiomeric excess [21]. 

Transition metal catalysts and biocatalysts can be combined in tandem in very effective ways as shown by the following example (Scheme 2.21). An immobilized rhodium complex-catalyzed hydrogenahon of 46 was followed by enzymatic hydrolysis of the amide and ester groups of 47 to afford alanine (S)-9 in high conversion and enanhomeric excess. Removal of the hydrogenation catalyst by filtration prior to addition of enzyme led to improved yields when porcine kidney acylase 1 was used, although the acylase from Aspergillus melleus was unaffected by residual catalyst [23]. 

Hydroboration. Although hydroboration seldom requires a catalyst, hydrobora-tion with electron-deficient boron compounds, such as boric esters, may be greatly accelerated by using transition-metal catalysts. In addition, the chemo-, regio- and stereoslectivity of hydroboration could all be affected. Furthemore, catalyzed hydroboration may offer the possibility to carry out chiral hydroboration by the use of catalysts with chiral ligands. Since the hydroboration of alkynes is more facile than that of alkenes the main advantage of the catalytic process for alkynes may be to achieve better selectivities. Hydroboration catalyzed by transition-metal complexes has become the most intensively studied area of the field.599... 

The first chiral transition-metal catalyst designed for an enantioselective transformation was applied to the reaction between a diazo ester and an alkene to form cyclopropanes [1]. In that application Nozaki and coworkers used a Schiff base-Cu(II) complex (1), whose chiral ligand was derived from oc-phenethylamine, to catalyze the cyclopropanation of styrene with ethyl diazoacetate (Eq. 5.1) [2],... 

Propargylic compounds (2-alkynyl compounds) are derivatives of alkynes and they undergo several types of transformations in the presence of transition metal catalysts. However, catalytic reactions of propargylic compounds, particularly their esters and halides, clearly differ mechanistically from those of simple alkynes, except in a few cases. Therefore, the catalytic reactions of propargylic compounds are treated independently from those of simple alkynes. The most extensive studies have been carried out using Pd catalysts, and mainly Pd-catalysed reactions are treated in this chapter [1],... 

Catalytic hydroboration of vinylic ethers, acetals, and esters with pinacolborane takes place smoothly in the presence of transition metal catalysts. However, a noticeable exception is the catalytic hydroboration of vinyl bromides 59 which do not furnish the expected hydroborated product under these conditions. The reaction of vinyl bromides with pinacolborane initially affords the expected /3-boronoalkylbromide 60. A fast. -elimination ensues to furnish the terminal alkene 61 and 7 -bromopinacolborane 63. The alkene 61 undergoes hydroboration with unreacted pinacolborane to provide the debrominated boronate 62. The intermediate 5-bromopinacolborane 63 cleaves the ethereal C-O bond in the solvent (THF) to provide 4-bromobutyl borate 64 as a side product (Scheme 11) <1996JA909, 2000CSP14505>. 

This chelation-assisted C-H/olefin and C-H/acetylene coupling can be applied to a variety of aromatic compounds with a directing group such as ester, aldehyde, imine, azo, oxazolyl, pyridyl, and nitrile [7]. In this section, we describe the coupling reactions of aromatic carbonyl compounds with olefins using a transition metal catalyst. 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

Fortunately, though, there is one borane, catecholborane (A in Figure 16.15), that adds to C=C triple bonds but not to C=C double bonds (in the absence of transition metal catalysts). This reagent adds to alkynes with cw-selectivity, so that the reaction stops at the stage of trans-alkenylboronic acid esters (B in Figure 16.15). 

Intramolecular Kharasch -type cyclizations.2 Unsaturated a,a-dichloro esters or carboxylic acids undergo cyclization in the presence of various transition metal catalysts, particularly Cl2Ru[P(C6H5)3]3 or Cl2Fe[P(OC2H5)3]3.3 Thus ethyl 2,2-dichloro-6-heptenoate (2) in the presence of 1 cyclizes rapidly to the cis-l,2-disub-... 

The selective oxidation of alkanes represents one of the most important and difficult challenges in the chemical industry, and significant recent attention has focused on the use of electrophilic late-transition-metal catalysts to achieve this goal [105-109]. These reactions are often performed in strong-acid solvents that enhance the electrophilicity of the metal center. The use of these solvents also results in formation of alkyl ester products that are deactivated toward further C - H oxidation. 

An excellent method for cleaving benzylic ethers, esters, carbamates, and amines uses hydrogen In the presence of a transition metal catalyst such as Pd. Alternatively a process known as catalytic transfer hydrogenation can be employed which uses 1,4-cyclohexadiene, cyclohexene, formic acid or ammonium formate as the source of hydrogen24 The method Is exceptionally mild and compatible with most functional groups devoid of unsaturation. Hydrogenolysis of benzyloxycarbonyl (Z or Cbz) groups of amines was a major advance in the... 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

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