Methyl-477-pyran-2,6-dicarboxylate

Pyran-2-ones 796 can undergo Diels-Alder reaction with dimethyl acetylene dicarboxylate to afford dimethyl 3-methyl-isocoumarin-5,6-dicarboxylate in modest yield (Equation 330) <2003JOC1729>. 

To illustrate the practical use of the three programs [143], a dihydropyran derivative, ethyl-2-methyl-5,6-dihydro-o -pyran-6,6-dicarboxylate has been chosen as an example. This unsaturated, sugar-related compound in solution exists in an equilibrium of two conformations. 

Fig. 10.48. Conformations of ethyl 2-methyl-5,6-dihydro-o -pyran-6,6-dicarboxylate.

C7H406 4-oxo-4H-pyran-2,6-dicarboxylic acid 99-32-1 25.00 1.5351 2 9988 C7H5CI3S methyl 2,4,5-trichlorophenyl sulfide 4163-78-4 25.00 1.4412 2... 

Catalytic cyclopropanation of alkenes with diazomalonates is sometimes carried out with copper powder, but it appears that copper(I) halide/trialkyl phosphite complexes (for a procedure see Houben-Weyl Vol. E19b, p 1113), bis(acetylacetonato)copper(II), " ° and tet-raacetatodirhodium can be employed more advantageously (Table 13, entries 7-9). For the cyclopropanation of styrene with dicyclohexyl diazomalonate, however, copper(I) triflate was the catalyst of choice, while intramolecular C —H insertion at the cyclohexyl ring took place in the presence of tetraacetatodirhodium. A detailed comparison of copper catalysts for the cyclopropanation of cyclohexene, 1-methyl- and 1,2-dimethylcyclohexene, (Z)- and ( )-hept-2-ene with dimethyl diazomalonate, including competitive reaction pathways such as allylic C-H insertion and carbene dimer formation, is available. The catalyzed interaction between diazomalonic esters and enol ethers leads to cyclopropanes in some cases (e.g. ethoxymethylenecyclohexane to dimethyl 2-ethoxyspiro[2.5]octane-l,l-dicarboxylate ) and to different products in other cases (e.g. 1-methoxycyclohexene, 2-methoxy-3,4-dihydro-2/7-pyran ). This behavior is attributed to the occurence of stabilized dipolar intermediates in these reactions. 

The dimethylamino group in diethyl (2 R=Et) and dimethyl 1-dimethylamino-3-oxobut-l-ene-2,4-dicarboxylates (2 R=Me) can be exchanged very easily with nitrogen nucleophiles. With primary amines in methanol or ethanol under reflux for several hours, substitution of the dimethylamino group by an amine takes place followed by intramolecular nucleophilic attack of the amino group on the ester to afford 1-substituted 5-alkoxycarbonyl-4-hydroxypyridin-2(lH)-ones 56 in 16-93% yields (5cheme 21). In the reaction of 56 with methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate (57), first the intermediate 58 was formed, which cyclized into 6-substituted 3-benzoylamino-8-ethoxycarbonyl-2H,5H-pyrido[4,3-li]pyran-2,5-diones (59). However, with 3-dimethyla-mino-2-(methoxycarbonyl)propenoate (60) intermediate 61 is formed... 

The Drug Development Branch of the National Cancer Institute and our own laboratories demonstrated antitumor activity for divinyl ether maleic anhydride copolymers. Samples of polycarboxylic divinyl ether maleic anhydride copolymer hydrolysate (NSC 46015 pyran 3,4-dicarboxylic anhydride, tetrahydro-2-methyl-6-(tetrahydro-2,5-dioxo-3-furyl) of average MW 17000 to 36000 show a broad spectrum of antitumor activity against transplanted tumors and a good therapeutic index. 

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