Esters heteroaryl

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

An interesting class ot covalent Inflates are vin l and ar>/ or heteroaryl Inflates Vinyl inflates are used for the direct solvolytic generation of vinyl cations and for the generation of unsaturated carbenes via the a-elimination process [66] A triflate ester of 2-hydroxypyridine can be used as a catalyst for the acylation of aromatic compounds with carboxylic acids [109] (equation 55)... 

Alkoxycarbonyl-Gruppen in Propargyl-Stellung konnen mit Aiuminiiimhydrid in Ather bei 20° selektiv zu den Hydroxymethyl-Gruppen reduziert werden3. Heteroaryl-acrylsau-re-ester werden von Natriumboranat selektiv zu Heteroaryl-propansaure-ester reduziert4. 

Heteroaryl- -ester 209 2-Methyl- -athylester 647 -methylester 645, 647, 663, 675 2-Methyl- -methylester 640... 

A further example of the utility of the cyclobuta[ >]chroman system in synthesis (see 6.4.1.3) is provided by the conversion of the cyclobutenedione derivatives (19) into substituted xanthones. Compounds (19) are obtained in high yield from salicylaldehydes and squarate esters and their reaction with alkenyl, aryl and heteroaryl li compounds is both facile and high yielding <96JA12473>. 

A mild and efficient a-heteroarylation of simple esters and amides via nucleophilic aromatic substitution has been described <06OL1447>. Treatment of 2-chloro-benzo[//Jthiazole 99 with tert-butyl propionate in the presence of NaHMDS under nitrogen furnishes tert-butyl 2-(benzo[c(jthiazol-2-yl)propanoate 100. When the same reaction is preformed initially under nitrogen and then exposed to air, the hydroxylation product 101 is obtained. This method offers two desirable features that are either complementary or improvements to the palladium-catalyzed a-arylation reactions. First, heteroaryl chlorides... 

A practical a-heteroarylation of simple esters or amides has been developed via nucleophilic aromatic substitution. Exposure of chlorothiadiazoles 317 and 319 to NaHMDS and tert-butyl acetate or iV-dimethylacetamide leads to the formation of functionalized... 

Pd-catalyzed carbonylation of heteroaryl halides provides a quick entry to heteroaryl carbonyl compounds such as heteroaryl aldehydes, carboxylic acids, ketones, esters, amides, a-keto esters and a-keto amides. In addition, Pd-catalyzed alkoxycarbonylation and aminocarbonylation are compatible with many functional groups, and therefore, are more advantageous than conventional methods for preparing esters and amides [78],... 

The resolution was then based on the enzymatic propanolysis of this derivative in dioxane as solvent. Lip Novozyme 435 selectively cleaves the L-form of the oxazolone producing an L-enriched (81-87% ee) 2-acetamido-3-(heteroaryl)propionic acid propyl ester, the dynamic aspect of the process being based on the continual racemization of the residual oxazolone. The propyl group was then removed with alkali and a second selective enzymatic step to remove the acetyl protecting group with Fluka Acylase 1 produced the L-amino acid at better than 99% ee (Scheme 13). 

Although other heteroatom and heteroaryl IV-ethylcarbazole oxime ester analogs have previously, the agents of the current invention have unusually high Stepwedge sensitivity. 

Oxime ester derivatives with heteroaryl components, (I), were previously prepared by the authors (1) and used in photoresist applications. 

A potential way to avoid the formation of undesired side products, like in 7.2., is the use of such boron compounds that have only one transferable group. In most cases boronic acids are the compounds of choice, as they are easy to prepare, insensitive to moisture and air, and usually form crystalline solids. In certain cases, however the transmetalation of the heteroaryl group might be hindered by the formation of stable hydrogen bonded complexes. In such cases the use of a boronate ester, such as in equation 7.4., provides better yields. For example pyridine-2-boronic acid dimethylester coupled readily with a bromoquinoline derivative under conditions similar to 7.3. (potassium hydroxide was used as base and tetrabutylammonium bromide as phase transfer catalyst).6... 

Vinylpyrroles and vinylindoles are extremely sensitive to acid-catalyzed dimerization and polymerization and it is significant that much of the early research was conducted on systems which were produced in situ. Even by this approach, the dimerization of, for example, 2-(3-indolyl)propene and l-(3-indolyl)-l-phenylethylene was difficult to prevent (see the formation of 110 and 120, Section 3.05.1.2.8). Similarly, although it is possible to isolate ethyl 2-(2- and 3-indolyl)propenoates, they appear to be extremely unstable at room temperature even in the absence of acid (81UP30500) to give [ 4 + 2] cycloadducts of the type (348) (cf. 77JCS(P1)1204>. For many years simple vinylpyrroles also eluded isolation, on account of their facile acid-catalyzed polymerization. Application of the Wittig reaction, however, permits the synthesis of vinyl-pyrroles and -indoles under relatively mild and neutral conditions (see Section 3.05.2.5). In contrast, heteroarylvinyl ketones, esters, nitriles and nitro compounds, obtained by condensation of the appropriate activated methylene compound with the heteroaryl aldehydes (see Section 3.05.2.5), are thermally stable and... 

The C-Si bonds of aryl-, heteroaryl-, vinyl-, and allylsilanes are stable towards alco-holates or weak reducing agents, but can be cleaved under mild conditions by treatment with acids or fluoride to yield a hydrocarbon and a silyl ester or silyl fluoride. Several linkers of this type have been tested and have proven useful for the preparation of unfunctionalized arenes and alkenes by cleavage from insoluble supports. Typical loading procedures for these linkers are sketched in Figure 3.42. 

Peptide a-oxo acids 1 (R4=H), a-oxo esters 1 (R4= alkyl or substituted alkyl), and a-oxo-amides 2 (R5=R6=H, alkyl, substituted alkyl, aryl, and/or heteroaryl) are potent reversible inhibitors for cysteine and serine proteases (Scheme 1).[1 9 Their inhibitory potency is the result of their enhanced electrophilic a-carbonyl functional group that can better compete with the substrate in the formation of a tetrahedral adduct with the cysteine or serine residue at the protease active site. In the case of peptide a-oxo esters and a-oxoamides, the extension in PI and beyond gives the inhibitors additional interactions with the protease at the corresponding sites. 

For example, /3-keto esters and /3-keto anilides react with both C-heteroaryl- and JV-heteroarylhydrazonoyl halides 5a,d,f and 28a to yield pyrazole derivatives 225-227 (77HCA2171 80JHC209 87JHC1665 88H695). 

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