Ethyl cyanoformate, cycloaddition

When 4-nitrobenzyl isocyanide reacts with an arylsulfenyl chloride it is converted into an A -(4-nitrobenzyl)-S-arylisothiocarbamoyl chloride. In the presence of triethylamine a solution containing the 1,3-dipolar species (26) is obtained. If (26) is generated in the presence of ethyl cyanoformate, cycloaddition gives an imidazole (Scheme 4,2.12) [37]. Reactions are performed at 60°C in the presence of a large excess of the dipolarophile, and yields are reported in the range 38-50%. 

Photolysis of 2,3-diphenyl-A -azirine (442) generates benzonitrile ylide (443). Irradiation in the presence of ethyl cyanoformate resulted in a mixture of the oxazoline (444) and the imidazole (445) by 1,3-dlpolar cycloaddition to the carbonyl and nitrile group, respectively (72HCA919). 

In contrast, the 5-phenyliminothiatriazoline (323) reacts as a masked 1,3-dipole with a variety of electrophilic nitriles. Tosyl cyanide and ethyl cyanoformate both react with (323) in refluxing chloroform to give initially (324) which then isomerizes to (325) as the reaction proceeds (Scheme 71) <91JHC333>. When the solvent is changed to acetone the reaction with the nitriles proceeds faster due to the formation of the adduct (326) which is capable of undergoing cycloaddition/elimination reactions at 20 °C. Trichloroacetonitrile does not react with (323) in chloroform solution in acetone,... 

Compounds 98 behave as 1,3-dipoles in cycloaddition reactions with DMAD, ethyl cyanoformate, and alkenes the structure of the adduct 186 from ethyl cyanoformate suggests that reaction is via form 98b.131... 

Considerable variation is also possible in the carbonyl function, and in addition to simple aldehydes and ketones, acetyl cyanide,292 diethyl oxomalonate,293 diethyl oxalate,294 and ethyl cyanoformate 295 [Eq. (77)] will all undergo cycloaddition to alkenes to form the corresponding oxetanes. Oxetanes are also formed in certain circumstances from both a,j8-unsaturated aldehydes298 and acetylenic ketones.297... 

A 1,4-dipolar cycloaddition between tetrahydropyrido[l,2-a]pyrimidi-none 114 (R = Me) and 4-methyl-l, 2,4-triazoline-3,5-dione 666gave stable adduct 667 in acetonitrile or in acetic acid at room temperature for 1 hour (Scheme 44) (85CB4567). When ethyl cyanoformate was used as dienophile in boiling toluene for 20 hours, ethyl 3-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[ 1,2-a]pyrimidine-2-carboxylate 669 was obtained (86CB1445). Pyrido[l,2-a]pyrimidine-2-carboxylate 669 was formed from the initial adduct 668 by elimination of phenyl isocyanate. Reaction of tetrahydropyr-ido[l,2-a]pyrimidinone 114 (R = Me) with l-(diethylamino)-l-propyne in... 

Treatment of the imidoyl chloride (106) with triethylamine yields the nitrile ylide (107), which undergoes cycloaddition with a variety of reagents giving imidazole products. With ethyl cyanoformate a mixture of esters is obtained with 2,4-xylyl cyanate the 4-aryloxy... 

Reaction of 5-amino-l -benzyl-4-imidazolecarboxylic acid 495 with 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine 496 at 80 °C in DMF led to 9-benzyl-2,6-bis(ethoxycarbonyl)purine 501 in 83% yield. Presumably, 5-amino-l-benzyM-imidazole 497 is generated siVu from the acid and is highly reactive for the cycloaddition. The cycloadduct 498 then spontaneously undergoes retro Diels-Alder reaction with the loss of ethyl cyanoformate 499 followed by the loss of ammonia and aromatization to produce the purine in a regioselective manner (Scheme 114) <1999JA5833, 2005JOC998>. 

When triethyl l,3,5-triazine-2,4,6-tricarboxylate is treated with acetimidamide hydrochloride7 or propionimidamide hydrochloride8,9 in dimethylformamide at 90-100°C the corresponding pyrimidines are formed in 80-85% yield. The reaction proceeds by reversible in-situ tautomerism of the amidine hydrochloride to the alkene-1,1-diamine and its participation in a [4 + 2] cycloaddition with the triazine. The cycloaddition is followed by a retro Diels-Alder reaction with loss of ammonia and ethyl cyanoformate. The thermal conditions (>80°C) required for effecting the retro-Diels-Alder reaction and the deliberate use of the amidine hydrochlorides facilitates the amidine tautomerism and seems to be essential for aromatization of the initially formed cycloadduct.7-9... 

Cycloaddition reaction of triethyl 1,3-5-triazinetricarboxylate (585) with 1,1-diamino-ethene, which is generated in situ from acetamidine hydrochloride, provides an adduct (586) which subsequently eliminates ammonia (587) and undergoes a retro Diels-Alder reaction with loss of ethyl cyanoformate, thereby forming the pyrimidine (588). The reaction sequence is highly dependent... 

Furan has been found to form oxetanes with a variety of carbonyl compounds, e.g., ketones,202-205 aldehydes,206 and ethyl cyanofor-mate.207 In most reactions the (2 + 2)-cycloaddition occurred specifically to give a 2,7 dioxabicyclo[3.2.0]hept-3-ene (175) rather than the 2,6-isomer (176). Only the addition of ethyl cyanoformate yielded mixtures of 175 and 176 (R = OEt and R2 = CN), in a ratio of 2 l.207 Two subsequent (2 + 2)-cycloadditions of benzophenone and furans have been reported to give two isomeric products, 177 and 178.205 Substituted furans yielded similar oxetanes.203 Benzo[ >]furans, furo-coumarins, and furochromones also proved to undergo (2 + 2)-cyclo-addition reactions with carbonyl compounds such as ketones, aldehydes, and quinones. Invariably one type of oxetane was formed (179).,37,u3 ,44 200-202 208,20, In the case of 2-methoxycarbonylbenzo[6)-furan, evidence has been provided that the oxetane was produced by addition of the excited triplet state of the olefinic reactant to the ground state of the ketone.208... 

Ethyl cyanoformate reacts particularly smoothly with aryl nitrile sulfides, yielding 349.247 The isomeric 5-aryl-l,2,4-thiadiazole-3-carboxylates (352) are formed analogously by the cycloaddition of ethoxycarbonylnitrile sulfide... 

A detailed study of the scope of the amidine Diels-Alder reaction of 1,3,5-triazines has been carried out. The thermal reaction of amidines with symmetrical 1,3,5-triazines proceeds with in situ amidine to 1,1-diaminoethene tautomerism, [4+2] cycloaddition, loss of ammonia with imine generation, imine to enamine tautomerism, then retro-Diels-Alder loss of ethyl cyanoformate to yield substituted 4-aminopyrimidines. 

Axially chiral pyridines as well as axially chiral pyridones could be synthesized via rhodium-catalyzed enantioselective [2 + 2 + 2] cycloaddition. The reaction of 1,6-diyne 68 with ethyl cyanoformate (69) in the presence of the cationic rhodium(I)/Segphos catalyst furnished axially chiral arylpyridine 70 as a single regioi-somer with excellent ee value (Scheme 9.25) [19],... 

In the axially chiral biaryl synthesis via the double [2 - - 2 - - 2] cycloaddition shown in Scheme 9.18, the use of ethyl cyanoformate (69) instead of monoynes furnished the corresponding C2-symmetric axially chiral pyridines 71 with excellent enantios-electivity, although the yield of 71 was low, due to the formation of regioisomeric by-products (Scheme 9.26) [19],... 

Fordyce et al. (2010) have enveloped an improved method for the synthesis of isothiazoles and 1,2,4-thiadiazoles. The 1,3-dipolar cycloaddition reactions of nitrile sulfides, generated by microwave-assisted decarboxylation of 1,3,3-oxathiazal-2-ones have been studied. The adducts l,2,4-thiadiazole-5-carboxylates were synthesized by cycloaddition of the nitrite sulfides to ethyl cyanoformate. 

Cycloadditions. Methyl and ethyl cyanoformate have been reported to undergo [4 + 2] cycloadditions, e.g. with cyclopentadienones and 2-alkyl-l-ethoxybuta-1,3-dienes to form pyridines (eq 21), and with cyclobutadienes to form Dewar pyridines (eq 22). Ethyl cyanoformate is also ein effeetive dipolarophile, undergoing 1,3-dipolar addition to azides (eq 23) and cyclic carbonyl ylides (eq 24). ... 

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