Ethoxycarbonyl functionality

A prominent structural feature of 21 and its precursor 22 is the trans C16-C17 trisubstituted double bond. The particular relationship between the ethoxycarbonyl function and the A16 17 double bond in 22 is significant because it satisfies the structural prerequisite for the Johnson ortho ester Claisen rearrangement transform.2130 Mixed ketene acetal 23 thus emerges as the immediate... 

The homology between 22 and 21 is obviously very close. After lithium aluminum hydride reduction of the ethoxycarbonyl function in 22, oxidation of the resultant primary alcohol with PCC furnishes aldehyde 34. Subjection of 34 to sequential carbonyl addition, oxidation, and deprotection reactions then provides ketone 21 (31% overall yield from (—)-33). By virtue of its symmetry, the dextrorotatory monobenzyl ether, (/ )-(+)-33, can also be converted to compound 21, with the same absolute configuration as that derived from (S)-(-)-33, by using a synthetic route that differs only slightly from the one already described. 

The reaction of 1-arylsulfonylaziridines 217 with dimethylsulfoniumethoxycarbonyl methylide 218 is a fairly general approach for stereoselective synthesis of 1-arylsulfonylazetidines 219 bearing an ethoxycarbonyl functionality (Equation 58) <1995J(P1)2605>. However, the products are obtained in moderate yields. The reaction involves a regioselective transfer of an ethoxycarbonyl-substituted methylene group from the ylide to 1-arylsulfonylaziridines. 

Very likely the ammonium fluorides are the proton sources and therefore the reason for incomplete conversions, since potassium fluoride in acetonitrile gives high yields in a very elegant [3 + 2]-annuIation process 87). It combines a Michael addition to a vinyl phosphonium salt with an intramolecular Wittig reaction and proceeds only in the presence of 18-crown-6 with satisfying yield. This cyclopentene synthesis has been executed in a repetitive manner to prepare linear triquinanes as illustrated in Scheme 6. Unfortunately, the sequence is non-stereoselective with regard to the ethoxycarbonyl functions. 

A highly exo-selective asymmetric hetero Diels-Alder reaction was the key step in D.A. Evans total synthesis of (-)-epibatidine. The bicyclic cycloadduct was then subjected to a fluoride-promoted fragmentation that afforded a (f-keto ester, which was isolated exclusively as its enol tautomer. The removal of the ethoxycarbonyl functionality was achieved using the Krapcho decarboxylation. Interestingly, the presence of a metal salt was not necessary in this transformation. Simply heating the substrate in wet DMSO gave rise to the decarboxylated product in quantitative yield. 

The formation of more complex derivatives, by similar reactions of more highly substituted pyridines, has been reported.32,33 Replacement of the ethoxycarbonyl function by other electron-withdrawing substituents (—COMe, —CN, — N02) is possible34 [Eq. (14)1. 

The tricyclic adduct (15e R = CH2CH20Bn,Me) closely resembling (15a) (Table 2) could be cleaved by t-BuOK in t-BuOH followed by treatment with Mel to afford dihydropyrroles (105 R = CH2CH2Bn,Me). The tricyclic adduct (15e R = H) also gave the pyrrolidine derivative (106) on treatment with tetrabutyltinhydride followed by acid hydrolysis. The relative stereochemistry of the ethoxycarbonyl functions is not lost during this particular desulfurization procedure <85T3537>. 

It had long been recognized that the efficiency of peptide synthesis could be dramatically increased with the development of reversible amine protections. This realization inspired Bergman to modify Fischer s ethoxycarbonyl function and... 

From amino- and alkoxybutenones and benzonitrile iV-oxide as well as from acetyl- and ethoxycarbonyl-iV-phenylnitrilamines and p-methoxyphenyl azide, the corresponding functional isoxazoles, pyrazoles, and tiiazoles were obtained (83DIS 83ZOR2281 92SC2902). 

The comparison between the cycloaddition behavior of simple diazoketones and of ethyl diazopyruvate 56 towards the same olefin underlines the crucial influence of the ethoxycarbonyl group attached to the carbonyl function. This becomes once again evident when COOEt is replaced by an acetal function, such as in l-diazo-3,3-di-methoxy-2-butanone 86 with enol ethers and acetates, cyclopropanes rather than dihydrofurans are now obtained 113). ... 

Ethoxycarbonyl chloride is, by virtue of resonance involving the ester function, less reactive than acetyl chloride, and the reagent has found application for selective O-acylation in the steroid field.34 With this reagent, methyl 4,6-O-benzylidene-a-D-glucopyranoside yielded35 2- and 3-esters in the ratio 24 1, and the related benzyl-thiocarbonyl chloride gave the 2-ester in 58% yield.36... 

Sekine, M., Mori, H., and Hata, T., Protection of phosphonate function by means of ethoxycarbonyl group. A new method for generation of reactive silyl phosphite intermediates, Bull. Chem. Soc. Jpn., 55, 239, 1982. 

The downward systemic movement of ONCOL (structure given earlier), a new insecticide derived from carbofuran, has been observed (19). A significant amount of radioactivity was observed in the roots of cotton and bean plants treated topically at the base of bifoliate or trifoliated leaves with [carbamate carbonylONCOL. Downward movement of the radiolabeled material may be explained by hydrolytic degradation of the ethoxycarbonyl moiety in ONCOL to the carboxylic acid derivative, the acid function serving as a downward moving carrier. 

The related cyclization of 2-ethynylanilines 67 also represents one of the usefiil methods for the synthesis of 2-substituted indoles since the precursors are easily prepared from 2-haloanilines 66 by Pd-catalyzed cross-coupling with terminal alkynes. Althou cyclizations of such alkynes are normally effected using Cu(I) or Pd(II) species, Sakamoto showed that in the absence of such metals, base catalysis (e.g., NaOEt) alone can accomplish the same goal. This author now reports that tetrabutylammonium fluoride (TBAF) is capable of inducing cyclization to the indoles 68 without affecting functionalities such as bromo, cyano, ethoxycarbonyl, and ethynyl <99JCS(P1)529>. 

Tsuji has reported the cyclization/distannylation of bis( 1,3-dienes) that form bis(functionalized) 1,2-dialkenyl-cycloalkanes, although the scope of the transformation was quite limited.In one example, reaction of ( , )-6,6-bis(ethoxycarbonyl)-l,3,8,10-undecatetraene and hexamethyldistannane (1.2equiv.) catalyzed by Pd(DBA)2 in toluene at room temperature for 20h gave /ra/ i--( ,Z)-l,2-bis-[2-(trimethylstannyl)vinyl]cyclopentane trans- E,Z)-108] in 90% yield as a single regioisomer and diastereomer (Equation (69)). 

Nucleophilic processes that introduce chlorine include displacement of diazonium functions, but these are not well known in the imidazoles because of the instability of many simple aminoimidazoles. In one instance the lack of success may have been a function of the high stability of 5-ethoxycarbonyl-4-diazoimidazole. Other 1-substituted 4-diazonium salts showed expected reactivity, and 1-substituted 5-aminoimidazoles formed sufficiently reactive diazonium salts to give good yields of the 5-chloro compounds [80JCS(P1)2310]. Most of the thrust in this reaction strategy has focused on the preparation of fluoroimidazoles (see B,2,d). 

A small group of cyclic thioureas have been used in the treatment of excessive thyroid function. They include 6-n-propylthiouracil (176 R1 = H, R2 = Prn), 5-iodo-2-thiouracil (176 R1 = I, R2 = H), l-methyl-2-mercaptoimidazole (methimazole) and its ethoxycarbonyl derivative carbimazole (177), which lacks the bitter taste of the unacylated compound. These compounds block the synthesis of thyroxin by inhibiting the oxidation of iodide to iodine and the oxidative coupling of iodotyrosine residues. 

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