Acetylenedicarboxylic esters reaction with

Such reactions occur readily with alkynic esters, but the products isolated are often complex. Thus, the initial Michael adduct of type (68) from pyridine with acetylenedicarboxylic ester reacts with more alkynic ester to yield (66), (67) and other products. Quinoline and isoquinoline react similarly. 

Both acetylenedicarboxylic acid and its ester undergo Michael addition reactions with a variety of nucleophilic reagents. An example is... 

The imine (161), obtained from 1-aminopyridinium iodide and potassium carbonate, combines with dimethyl acetylenedicarboxylate yielding in the first place (162) which then with more ester gives dimethyl fumarate and the pyrazolopyridine (163), isolated in 15% yield. A corresponding reaction with isoquinoline imine gave 75% of the primary adduct [(cf. (162)]. ... 

Reaction of the mesoionic oxazolone 620 with acetylenedicarboxylic ester 621 gave the cycloadduct 622 in aprotic solvents and the Michael adducts... 

These reactions are found to be promoted by electron-donating substituents in the diene, and by electron-withdrawing substituents in the alkene, the dienophile. Reactions are normally poor with simple, unsubstituted alkenes thus butadiene (63) reacts with ethene only at 200° under pressure, and even then to the extent of but 18 %, compared with 100% yield with maleic anhydride (79) in benzene at 15°. Other common dienophiles include cyclohexadiene-l,4-dione (p-benzoquinone, 83), propenal (acrolein, 84), tetracyanoethene (85), benzyne (86, cf. p. 175), and also suitably substituted alkynes, e.g. diethyl butyne-l,4-dioate ( acetylenedicarboxylic ester , 87) ... 

Acetylenedicarboxylic acid, dimethyl ester, 50, 25, 36 Acetylenes, reaction with tri-methylsilyl azide, 50, 109 Acetylenic sulfonium salts, furans from, 53, 3 2-Acetylindane-l,3-dione, 52, 4 2-ACETYL-6-METHOXYNAPHTHALENE, 53, 5... 

Addition of nitroalkanes 402 (R = Me, Bu, Ph etc.) to methyl acrylate without a solvent in the presence of Amberlyst-21 gives good yields of the esters 403436. An analogous reaction with electrophilic acetylenes, e.g. dimethyl acetylenedicarboxylate, in the presence of potassium fluoride and tetrabutylammonium chloride yields adducts 404 as mixtures of geometrical isomers437. 

Wittig reactions with pyrrole-2-aldehyde led to the esters (79) which were cyclisized to 3a-azaazulen-4-ones (80).104,105 4-Methylene-3a-aza-azulenes (81) have been obtained from 80 with stabilized phos-phoranes.36 Reaction of dimethyl acetylenedicarboxylate with 81 could not be achieved. A similar cycloaddition was successful in the synthesis of cycl[3,3,3]azines (2) (Section V). 

Diels-Alder reactions of thiophene 1,1-dioxides are very common (B-67MI31401). With rare exceptions, the adduct loses a molecule of SO2 to form a diene which may add another molecule of the dienophile. The sequence with maleic anhydride is shown in Scheme 193. It has been claimed that in the reaction of thiophene dioxide with acetylenedicarboxylic ester the primary adduct could be isolated, but this could not be substantiated (75RTC85). 

Functionalization of Ni(MeCOCHCOMe)2 occurs in reactions with isocyanates, diethyl azodi-carboxylate and dimethyl acetylenedicarboxylate, which proceed by formal insertion of the methine C—H unit into the substrate multiple bonds to form respectively amides and ester-substituted hydrazines and alkenes. Similar additions of acetylacetone to these electrophiles is catalyzed by nickel acetylacetonate.217,218... 

Nitrodienes undergo intermolecular Diels-Alder reactions with appropriate dienophiles. The resulting nitro compounds can then be cyclized via a nitrile oxide intermediate.49 Thus, the 2-chloroacrylonitrile Diels-Alder adduct of 8-nitro-l,3-octadiene was prepared and cyclized to give (105) as a 3 1 mixture of diastereomers (Scheme 30). The Diels-Alder adduct of dimethyl acetylenedicarboxylate and 8-nitro-l,3-octadiene cyclized exclusively at the conjugated double bond, activated by the ester groups. Similarly, the quinone Diels-Alder adduct (106) cyclized at the conjugated double bond reduction of the conjugated double bond permitted cyclization on the cycloalkenyl double bond. 

The reaction of 1,8-naphthylenediamine with acetylenedicarboxylic ester leads to the mixture of compounds 519-521. The major products of this reaction are compounds 520 and 521, whereas 1,4-diazepine derivatives 519 are formed in a yield of 1% only (86MII). Structure 522 proposed for one of the products is incorrect (NK2161,62NKZ597 83BCJ2338 86MI1). 

The construction of a thieno[3,2-Z>]pyridine by pathway M involves the successive formation of the N(l)-C(2) and C(3)-C(4) bonds of the pyridine fragment. Various 3-aminothiophene-2-carboxylic acid derivatives are most often used as the starting reagents with 2C-components, which introduce carbon atoms C(2) and C(3) into the pyridine ring. For example, the reaction of amino ester 155 with dimethyl acetylenedicarboxylate (156) involves intramolecular cyclocondensation followed by hydrazinolysis to give derivatives of the new heterocyclic system thieno[2, 3 5,6] pyrido[2,3-<7]pyridazine (157) (1991JHC205, 1990SPH203). 

It was demonstrated some time ago that vinylic and cross-conjugated double bonds of protoporphyrin (IX) dimethyl ester (80a) constitute a diene system capable of undergoing Diels-Alder reactions with activated dieno-philes (68CC697). Isobacteriochlorins 81 and 82a were obtained in a reaction with dimethyl acetylenedicarboxylate (ACDE) and tetracyanoethene (TCNE), respectively (73JCS(PI)1424). 

Pyrroles can be -alkenylated by reaction with acetylenedicarboxylic ester, for example, to give an /Z mixture (1 3.3) of alkenes 110 (Scheme 48) <2006JOC7793>. 

Three reactions, which were known from the literature to be catalyzed by Lewis acids were selected as test reactions. A, was the Reetz alkylation of silyl enol ethers with -butyl chloride for which titanium tetrachloride is known to be useful [52]. B, was the Diels-Alder reaction between furan and acetylenedicarboxylic ester for which aluminium trichloride is a good catalyst [53]. C, was a Friedel-Crafts acylation for which aluminium trichloride is the preferred catalyst [54]. The reactions are summarized in Scheme 6. 

Addition to ot, -acetylenic esters and ketones (3, 108 6, 163-164). The addition of organocopper reagents to conjugated acetylenic carbonyl compounds is usually not stereospeciflc, although cis-addition predominates. Japanese chemists have found that the stereoselectivity in the reaction with alkylcopper reagents is markedly enhanced by use of the complex RCu BRj. Thus the reaction of dimethyl acetylenedicarboxylate with n-butylcopper complexed with tri-n-butylboron (or triethylboron) results in exclusive formation of the cis-adduct. In the absence of a trialkylborane the cis- and adducts are formed in the-ratio 85 15. 

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