Arylation cyanoacetate esters

Other nucleophiles than amines which have been employed in the reaction are malononitrile and cyanoacetic ester anions. Both of these anions undergo a preliminary reaction with the aryl halide to form the C-aryl derivatives before they attack the ir-allylpalladium intermediate, so that diarylated products are formed (equation 31).86 Phenylmalononitrile anion reacts with iodobenzene and butadiene to give the same product in 70% yield. 

In the presence of 18-crown-6, concurrent cyclization and arylation is favored over the Heck reaction of a terminal double bond of alkenyl cyanoacetic esters. 

Scheme 5.27 (DHQD)jPYR in reaction of benzyl a-aryl cyanoacetates 52 with a-imino ester 23n...

SCHEME 11.10. A -Nitrosoaldol reaction of a-aryl substituted cyanoacetate esters promoted by 14. 

Hydrolysis of the acyl, aryl or quaternary ammonium derivative of malonic ester, acetoacetic ester or cyanoacetic ester and of the phthal-imido, benzamido, acetamido, or a-oximino derivative of these esters. 

From N-Aryl-2-nilrosoanilines and Alkylated Cyanoacetic Esters... 

Although arylation or alkenylation of active methylene compounds can be carried out using a Cu catalyst, the reaction is sluggish. However, the arylation of malononitrile (390) or cyanoacetate proceeds smoothly in the presence of a base and Pd catalysts [189], Tetracyanoquinodimethane (392) is prepared by the coupling of / -diiodoben-zene with malononitrile (390) to give 391, followed by oxidation [190], Presence of the cyano group seems to be essential for intermolecular reactions. However, the intramolecular arylation of malonates, / -keto esters and /i-diketones proceeds smoothly [191]. The bromoxazole 393 reacts with phenylsulphonylacetonitrile (394)... 

For purposes of classification the 4-aminopyrazoles are considered to be 4-imino-2-pyrazolines and analogs of 2-pyrazolin-4-ones. These compounds are listed in Table XL. Such compounds can be prepared by direct cyclization using ethyl diazoacetate and ethyl cyanoacetate.92 This is the same as eq. 243, except that the malonic ester is replaced by ethyl cyanoacetate. Purines can be hydrolyzed to 4-imino-2-pyrazolines by using strong acid.1210 1846 By far the most frequently used preparation is reduction of appropriately substituted pyrazoles, such as 4-nitro,368,812,819,1015,1019,1049 4-nitroso1165 or 4-aryl-azo.671 974,995 The hydrolysis of the carbethoxy 4-imino-2-pyrazolines derived from ethyl cyanoacetate and ethyl diazoacetate forms 4-imino-2-pyrazolin-3-carboxylic acid which is readily decarboxylated to the parent compound.92... 

Amino-3-cyano-thiophenes or 2-amino-thiophene-3-esters result from this route, generally conducted as a one-pot process, involving a ketone that has an a-methylene, ethyl cyanoacetate or malononitrile, sulfur, and morpholine. Various improvements to the original procedure include using microwave irradiation on solid snpport, or with potassium fluoride on alumina as the base, or solvent-free,and using morpho-lininm acetate in excess morpholine for aryl alkyl ketones. 

Enolate Arylation Reactions. The direct coupling of aryl halides with enolates (or enolate equivalents) of ketones, esters, and amides is now well established. Malonic esters, cyanoacetates, and malononitrile can be arylated upon treatment with aryl halides in the presence of Pd(dba)2 and electron-rich phosphines or N-heterocyclic carbenes. Carbene ligands have also proven effective in promoting the a-arylation of protected amino acids. As a caveat to the use of Pd(dba)2, the arylation of azlactones in the presence of this palladium source and phosphines was less efficient than that with Pd(OAc)2. The dba ligands were found to react with azlactone substrates to form catalytically inactive palladium complexes. Diastereoselective enolate arylation has been achieved through the use of chiral auxiliaries appended to preformed enol silyl ethers (eq 23). The role of the zinc additive is not clear, however, it appears that discrete zinc enolates are not involved. 

Alkylation and Arylation. The 5-methylation of thioamides by diazomethane is catalysed by silica gel. 5-Phenyl derivatives of thiobenzanilides are obtained in high yield by radical arylation with nitrosoacetanilide or phenylazotriphenyl-methane. Thiols are made from alkyl (or cycloalkyl, or aralkyl) halides by their reaction with dimethylthioformamide and treatment of the imidium ester with methanol other methods of hydrolysis lead to side-reactions, giving impure products. Mono- and bi-protic thiocarboxamides condense with ethyl bromo-cyanoacetate and one equivalent of NaOEt with spontaneous separation of sulphur and the formation of ff-amino-cr-cyano-acrylates, as shown in reaction (5). The... 

Numerous CH insertion reactions of isocyanates involve substrates with a CH2CO group. For example, dialkyl malonates, malonitrile , ethyl cyanoacetate and oxaloacetic esters react with alkyl and aryl isocyanates at room temperature, in the presence of triethylamine, to give products resulting from insertion into the activated C-H bond as... 

Earlier, ester plasticizers of various types were also reported to prevent the gradual embrittlement of the adhesive bond on aging. Those reported include cyanoacetates, succinates, adipates, sebacates, phthalates, acyl esters, phosphonates, and phosphates. Alkyl aryl... 

Use of proline-catalyzed five-component cascade olefmation/Diels-Alder/ epimerization/olefination/hydrogenation reactions of enones, aryl aldehydes, alkyl cyanoacetates, and Hantzsch ester to furnish highly substituted 66 in a highly diaste-reoselective fashion (99% de) with excellent yields (70 to 75%) was also reported (Scheme 1.20) [23]. 

Alkylations and arylations Simple alkylations of [ " C]cyanoacetates are of lesser importance than of dialkyl [ C]malonates because the products, a-i Clcyanoalkanoic esters, are usually more readily available via [ " C]cyano-dehalogenation of a-bromo esters, or by alkoxy-carbonylation of alkyl [ " C]nitriles with chloroformates or dialkylcarbonates (analogous to Routes C and D in Figure 7.33). Both of these alternatives avoid problems... 

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