Dialkyl acetylenedicarboxylates

Reaction of pyridines with dialkyl acetylenedicarboxylates in the presence of isocyanates in dry CH2C12 at room temperature produced 1-substituted 2-oxo-l,9a-dihydro-2/7-pyrido[l,2-tf]pyrimidine-3,4-dicarboxylates <2004TL1803>. One-pot, three-component synthesis of 1-substituted 2-oxo-l,llb-dihydro-2//-pyrimido[2,l- ]iso-quinoline-3,4-dicarboxylates and 4-(3-chloro-4-methylphenyl)-3-oxo-4,4a-dihydro-3/7-pyrimido[l,2-tf]quinoline-l,2-dicarboxylate was realized by the reaction of isoquinoline and quinoline with isocyanates and dialkyl acetylenedicarboxylates <2004S861>. Diastereomeric mixtures of l-tosyl-2-aryl-l,llb-dihydro-2/7-pyrimido[2,Ttf]isoquinoline-3,4-dicarboxylates were obtained from isoquinoline, iV-tosyl-benzaldehyde imines, and DMAD <2002OL3575>. 

Isocyanides and dialkyl acetylenedicarboxylates in the presence of 2,4-dihydro-3//-pyrazol-3-ones 344 in acetone at ambient temperature undergo a smooth 1 1 1 addition reaction to produce highly functionalized 7-oxo-17/,7H-pyrazolo[l,2-tf]pyrazole derivatives 345 in 69-81% yields (Equation 47) <2005T3963>. 

Tandem reaction of aromatic aldehydes with electron-deficient acetylenes and dialkyl acetylenedicarboxylates in the presence of I it iN led to the formation of fully substituted furans in moderate yields. One appropriate example is shown below <06EJOC5174>. 

In the reactions of benzoyl isothiocyanate 324 and dialkyl acetylenedicarboxylates 325 in the presence of triphenyl-phosphine, 2-phenyl-4-thioxo-47/-l,3-oxazine-5,6-dicarboxylates 326 and dialkyl 2-(benzoylimino)-5-phenyM//-[l,3]dithiolo[4,5- ]pyrrole-4,6-dicarboxylates 327 were formed in a ratio of 1 3 (Equation 30) <2006TL2953>. 

Two one-pot syntheses of highly substituted pyran-2-ones have been published. One involves the reaction between t-BuNC, dialkyl acetylenedicarboxylates and bromomalonates <99JCR368>. In the other, cyclobutenediones are treated with 0-silylated cyanohydrins to yield a 4-acylcyclobutenone by a 1,4-silyl migration and cyanide displacement which rearranges to the pyranone (Scheme 18) <99JOC2145>. 

Similarly, when dialkyl acetylenedicarboxylates were condensed with 2,3-diaminopyridine in ethanol, the 2-carboxy-carbonylmethylene-l,2-dihydro-4/f-pyrido[2,3- ]pyrazin-3-ones 33 were obtained. The isomers 34 were formed when acidified ethanolic solution was employed <1995JHC1071>. 

In the manner already described i vide supra) for pyridazinopyridazines, pyrimido[4,5-f]pyridazines can be formed by reaction of a 4-hydrazinopyrimidine with a dialkyl acetylenedicarboxylate (Scheme 19) in principle, an indazole side product is possible, but this is not observed in practice <1999TL1793>. 

The reaction of indolizines with dialkyl acetylenedicarboxylates in the presence of a dehydrogenating catalyst leads to 1,2-dicarbalkoxycycl-[3,2,2]azines.22 23 Methyl phenylpropiolate may be used instead, although attempts to effect reaction between indolizine and certain other dienophiles including diphenylacetylene, diethyl azodicarboxylate, and 1,3-cyclohexadiene were unsuccessful. Hydrolysis of the diesters yielded the corresponding acids. Subsequent decarboxylation proceeded in high yield using copper chromite in quinoline [Eq. (5)]. 

Compound 34 has been obtained from 7-azaindolizine by treatment with dialkyl acetylenedicarboxylates and subsequent hydrolysis and decarboxylation (K. Untch, personal communication). 

The l-azacycl[3,3,3]azines (54a, b) were obtained from the reaction of dialkyl acetylenedicarboxylates and the quinolizine derivatives (53a, b) which resulted from reaction of 2-pyridinoacetonitrile with 2-... 

These compounds offer interesting possibilities for further elaboration as they enter into addition reactions with, for example, the 1,2-quinone (60), yielding tricyclic compounds (61) (79TL237), and their bicyclic analogues (62) combine with phenyl isocyanate to give adducts (63), which eliminate carbon dioxide to afford pyrimidine betaines (64). Similarly, dialkyl acetylenedicarboxylates produce quinolizinones (65) (Scheme 19) (79CB1585). 

Huisgen, Gotthardt, and Grashey518 have shown that 4,5-diphenyl-isosydnone (99) reacts with EPP in p-cymene at 150° giving the corresponding pyrazole ester (103) in 53% yield. Ohtaand Kato have stated 519 that these mesoionic-l,3,4-oxadiazoles do not react with dialkyl acetylenedicarboxylates either thermally or photochemically. McCarthy,... 

In a three component one-pot reaction, tert-butyl isocyanide, dialkyl acetylenedicarboxylates and salicylaldehydes react to afford 3-carboxycoumarins in high yield (Scheme 169) <2004S679>. 

Ir(Cl)(N2)(PPh3)2] reacts with dialkyl acetylenedicarboxylates to form complex (225) via N2 displacement. The complex (225) may react with an alkyne at 383 K to yield the iradacyclopen-tadiene complex (226) and then hexasubstituted benzenes (Scheme 23).501... 

A one-pot, three-component reaction of isocyanides 45, dialkyl acetylenedicarboxylates 46 and ethyl 2-oxo-2-(l,3-thiazol-2-ylamino)acetates 44 provides easy access to 5H-[1,3]thiazolo[3,2- pyrimidinc derivatives 52 <07SL2703>. Presumably, addition of... 

Cycloaddition of thiazolium azomethine ylides with dialkyl acetylenedicarboxylates 61 provides another approach to pyrrolo[2,1 -bjthiazoles 64 <070L4099>. Quatemization of 2-methylthiothiazole with trimethylsilylmethyl trifluoromethanesulfonate (TMSChkOTf) and subsequent fluoride-induced desilylation of the resulting (trimethylsilyl)methylammonium salt generate the acyclic azomethine ylide 62. This ylide readily participates in 1,3-dipolar cycloadditions with acetylene derivatives 61 to give adducts 63, which undergo spontaneous elimination of methylmercaptan to give the A-fuse cl thiazoles 64. ... 

Another novel multi-component reaction involving the synthesis of 4//-pyrido[ 1,2-ajpyrimidines 52, a motif found in many bioactive molecules, was reported by Adib et al. <07T11135 07TL4195>. The reaction involves the formation of a reactive 1 1 zwitterionic intermediate resulting from the addition of isocyanides 53 to dialkyl acetylenedicarboxylates 54 followed by trapping with A-(2-pyridyl)amidcs 55. 

Nucleophilic attack on the highly reactive 1 1 adducts produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates by 2-hydroxyketones leads to vinyltriphenylphosphonium salts, which undergo an intramolecular Wittig reaction to produce functionalized dialkyl 2,5-dihydrofuran-2,3-dicarboxylates in fairly high yields (Equation 61) <1998T9169>. 

Alkyl isocyanides, dialkyl acetylenedicarboxylates, and benzoyl cyanides undergo a three-component reaction to give highly functionalized iminolactones (Equation 69) <2006T1845>. 

Phosphazenes, derived from hydrazines and acetylenic esters, were employed in the regioselective synthesis of 5-pyrazolones and pyrazoles <1999T14451>. Reactions of isocyanides 637 and dialkyl acetylenedicarboxylates 638 in the presence of 1,2-diacylhydrazines 639 led to highly functionalized pyrazolines 640 (Equation 133) <2005TL6545>. 

Reaction of selenourea with dialkyl acetylenedicarboxylates affords 2-amino-4,5-dihydro-l,3-selenazol-4-ones 82 via 1 1 adducts in acetone solution or in solvent-free conditions. The reaction proceeds stereoselectively to afford the (Z)-stereoisomer (Scheme 15) <2005ZN569, 2005PS2439, 2005MI2371>. 

Attack on Unsaturated Carbon.- A versatile route to phosphinic acids (15) is the 1,4-addition of bis(trimethylsilyl) phosphonite (16) to a,p-unsaturated esters.The pyrophoric (16) was prepared in s/fu from triethylammonium phosphinate silylation and 1,4-addition can be repeated to give (17), or performed in one step if symmetrical phosphinic acids (17) are wanted. Tervalent phosphorus acid esters (18) react with dialkyl acetylenedicarboxylates in the presence of carbon dioxide to give 1,2-oxa-phospholenes (19) these reacted further with an excess of the phosphorus reagent to give different ylids, (20) or (21), dependant on the number of methoxy groups in (18). 

Treatment of trialkyl phosphites with dimethyl acetylenedicarboxylate in toluene at 80 °C in the presence of the fullerene, Ceo, results in the formation of the stabilised phosphite-ylides (81), involving a cyclopropane ring on the fullerene unit. These ylides readily undergo hydrolysis with hydrobromic acid to give the phosphonates (82) in good yield. Protonation of the initial adducts of trimethyl phosphite and dialkyl acetylenedicarboxylates by indane-1,3-dione leads to the formation of vinyltrimethoxyphosphonium cations. 

The reactions of trialkyl phosphites with dialkyl acetylenedicarboxylates have been studied in some detail, and the products explained as proceeding via 1 1 intennediates. Thus, the addition of a solution of dimethyl acetylenedicarboxylate to either (MeO 13 or (EtOjjP (2 eq) at 0°C leads to the formation of the corresponding 1,2-diphosphoranes. Treahnent of the diphosphorane with anhydrous HBr leads to protonation and subsequent dealkylation to give tetramethyl l,2-/ (meth-oxycarbonyl)-l,2-ethylenediphosphonate in 94% yield (Scheme 8.49). Trialkyl phosphites add vigorously to acetylenedicarboxylic acid in EtjO to give tetraalkyl 1,2-Z z5 (alkoxycarbonyl)-1,2-ethylenediphosphonates in modest yields. ... 

The reactive 1 1 intermediate formed in the initial reaction between trialkyl phosphite and dialkyl acetylenedicarboxylates can be trapped. Thns, reaction of dialkyl acetylenedicarboxylates with trimethyl phosphite in the presence of indane-1,3-dione leads to dimethyl 2-(3-methoxy-l-oxoindenyl)-l,2-fczXalkoxycarbonyl)ethylphosphonate in high yields. Treatment of trialkyl phosphites with Cgo and dimethyl acetylenedicarboxylate at 80°C give fullerenecyclopropyl phosphite ylides, which, on hydrolysis at ambient temperature, give the corresponding phosphonates. ... 

Addition of diethyl phosphite to ethyl propiolate or 3-substituted ethyl propiolates under basic conditions produces a mixture of mono- and bisphosphonyl esters. When p-enaminophospho-nates are allowed to react with an equimolecular amount of dialkyl acetylenedicarboxylate in THF at 50°C, substituted 2(l//)-pyridones containing phosphoryl and alkoxycarbonyl groups attached to the ring are obtained. ... 

Caesar. J.C.. Griffiths, D.V., Griffiths. P.A., and Tebby, J.C., Reactions of ylides formed from trialkyi phosphites with dialkyl acetylenedicarboxylates in the presence of carbon dioxide, J. Chem. Soc., Perkin Trans. 1. 2329, 1990. 

Reactions of Phosphines. - 1.2.1 Nucleophilic Attack at Carbon. Interest has continued in developing the synthetic applications of the 1 1 adducts of tertiary phosphines with dialkyl acetylenedicarboxylate esters. Protonation of the initial adduct from triphenylphosphine by phthalimide, followed by nucleophilic addition of the nitrogen of the resulting imido anion to the intermediate vinylphosphonium salt, has given the stabilised ylide system (189). ° Similar reactions with isatin and 3-chlorotetrahydrofuran-2,4-dione have given the yl-... 

Stable phosphorus ylides (50) and (51) have been prepared from the reaction of electron-deficient acetylenic esters, such as dialkyl acetylenedicarboxylates or alkyl propiolates and triphenylphosphine in the presence of 3-chlorotetrahyd-rofuran-2,4-dione (Scheme 10). These reactions are thought to proceed via vinylphosphonium salt intermediates which undergo Michael addition with the conjugate base of the CH-acid. Similar methodology has been used to prepare phosphonium ylide (52) from triphenylphosphine, isatin (indoline-2,3-dione) and dimethyl acetylenedicarboxylate. " ... 

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