Carboxylic esters coupling

The reductive coupling of aldehydes or ketones with 01, -unsaturated carboxylic esters by > 2 mol samarium(II) iodide (J.A. Soderquist, 1991) provides a convenient route to y-lactones (K. Otsubo, 1986). Intramolecular coupling of this type may produce trans-2-hy-droxycycloalkaneacetic esters with high stereoselectivity, if the educt is an ( )-isomer (E.J. Enholm, 1989 A, B). 

The Japp-Klingeraann coupling of aryidiazonium ions with enolates and other nucleophilic alkenes provides an alternative route to arylhydrazones. The reaction has most frequently been applied to P-ketoesters, in which deacylation follow S coupling and the indolization affords an indole-2-carboxylate ester. 

If there is no phenyl substituent in the 3-position the amination ability decreases. The acyloxaziridine (104) yields only 11% of a semicarbazide derivative with piperidine. In the presence of strong bases an intramolecular amination competes. Compound (104) reacts with methoxide within a couple of seconds to give phenylhydrazine carboxylic ester (106), and with cyclohexylamine to give the substituted semicarbazide (107). A diaziridinone (105) is assumed to be the common intermediate, formed by an intramolecular reaction from deprotonated (104) (67CB2600). 

Imidazole-2-carboxylic acid, 4-methylr ethyl ester synthesis, 5, 474 Imidazole-4-carboxylic acid coupling, 5, 403 iodination, 5, 400 reactions... 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

Coupling of Organometallic Reagents With Carboxylic Esters... 

The alkylation of activated halogen compounds is one of several reactions of trialkylboranes developed by Brown (see also 15-16,15-25,18-31-18-40, etc.). These compounds are extremely versatile and can be used for the preparation of many types of compounds. In this reaction, for example, an alkene (through the BR3 prepared from it) can be coupled to a ketone, a nitrile, a carboxylic ester, or a sulfonyl derivative. Note that this is still another indirect way to alkylate a ketone (see 10-105) or a carboxylic acid (see 10-106), and provides an additional alternative to the malonic ester and acetoacetic ester syntheses (10-104). 

Case I. First of all, we systematically introduced perturbation at coupled ff-systems (e.g. ethylene, butadiene, hexatriene and combinations of them) by substituting hydrogen for functional groups (classified by K. N. Houk as C-, Z- and X-substituents ), especially by methyl phenyl and carboxylic ester groups. We have so far introduced perturbations in the rr-system by replacing carbon atoms by heteroatoms (N and 0) in the rr-system skeleton. 

Attempts to prepare fluorothiophenes from diazonium salts (the fluoro-borate and hexafluorophosphate salts) have met only variable success. Methyl 3-fluorothiophene-2-carboxylate (32) was obtained in 89% yield by this method (Scheme 12), but the 3-diazonium salt of the corresponding 4-ester could not be isolated. Furthermore, the methyl ester of 2-diazothiophene-3-carboxylic acid coupled before decomposition could be attempted [85H(23) 1431]. 

Coupling of Organometallic Reagents with Carboxylic Esters Alkyl-de-acyloxy-substitution... 

Coupling of Organometallic Compounds with Aryl Halides, Ethers, and Carboxylic Esters Alkyl-de-halogenation. etc. 

The N-terminal amino group or a Lys residue can easily be used to label the PNA. This can be carried out in solution after purification, or more conveniently, while the PNA is still attached to the resin. Fluorescein and rhodamine are the most common fluorophore labels, while biotin is the most common affinity tag. Fluorescein or rhodamine are usually coupled to the amino group as -OSu esters or isothiocyanates. 4,4 -Dimethoxytrityl-protected biotin and Piv-pro-tected fluorescein have also been coupled to the N-terminus of a PNA as their 1-phenylpyr-azolin-5-one carboxylate esters.147 In 1997 a new fluorescein-conjugated Lys monomer (21, Scheme 12) was described. 48 ... 

A further general route to the 1,2-dicarbonyl system involves the oxidation of a-ketols (acyloins) (cf. the preparation of benzil from benzoin, Expt 6.143). The acyloins may be prepared from carboxylate esters by a radical coupling reaction involving the use of finely divided sodium metal in anhydrous ether, benzene, or toluene.144... 

This chiral column has been shown successfully to resolve enantiomeric mixtures (or racemates) of aromatic alcohols including l,l -bi-2-naphthol and its analogues (p. 836), aromatic hydroxy (or alkoxy) carboxylic esters and amides, amino acid derivatives, sulphoxides, cyclic imides and amides, lactones, etc. Even this list should not be regarded as limiting. The potential of this method, coupled with the simplicity of operation will undoubtedly be extensively developed and explored in the coming years. 

The reaction of TFP resin with sulfonyl chlorides (3 equiv.) in the presence of diisopropylamine (DIEA 3 equiv.) provides the corresponding sulfonate-activated resins (Fig. 2). Alternatively, sulfonic acids may be loaded directly onto TFP using DIC (via the intermediate sulfonic acid anhydride) as the coupling reagent. Analogous to the carboxylate esters, the sulfonate ester resins are stable when dry and may be kept at room temperature for an extended period of time without decomposition. This is one of the clear advantages of the polymeric TFP reagents versus acid chlorides the latter decompose once exposed to air and moisture. 

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