Isoquinoline reaction with dimethyl acetylenedicarboxylate

Tominaga and coworkers322 prepared dimethyl dibcnzo (t,/j]cycl[3.2.2]azinc-l,2-dicar-boxylate (553) by an [8 + 2] cycloaddition reaction of 1 -cyanoisoindolo[2,1-a isoquinoline (552) with dimethyl acetylenedicarboxylate (57), followed by elimination of HCN. A small amount of acetic acid was added to improve the yield of the reaction from 1% to 26%. The double adduct 554 was isolated in minor amounts (equation 159). 

Another nice example of SRR is depicted in Scheme 8. The original reaction was developed by Diels and Harms in 1936 [61]. Reaction of isoquinoline 71 with dimethyl acetylenedicarboxylate (DMAD, 72) initially forms zwitterionic intermediate 73, which is reacted with a second equivalent of DMAD to form benzoqui-nolizine 74. This is, however, not a true 3CR reaction, since two components are identical. In 1967, Huisgen reported three variations of this reaction in which... 

In 1967, the formation of diethyl 4,5,6,7-tetrafluoro-benzo[h]thiophen-2,3-dicarboxylate 259 in 49 % yield, by the reaction of lithium pentafluorobenzenethiolate with diethyl acetylenedicarboxylate in THF under reflux, was reported [ 124], Later, the cyclization reaction was shown to occur under very mild conditions (-70 to -58 °C) in 74 % yield [125], A similar reaction of lithium l,3,4,5,6,7,8-heptafluoro-2-naphthalenethiolate and its isoquinoline derivative with dimethyl acetylenedicarboxylate was reported to give polyfluorinated condensed products 261 and 262 [126],... 

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)]. ... 

Such reactions occur readily with alkynic esters, but the products isolated are often complex. Thus, the initial Michael adduct of type 79 from pyridine with dimethyl acetylenedicarboxylate reacts with a second equivalent of alkynic diester to yield 80, and thence 81 and other products. Quinoline and isoquinoline react similarly. 

In some cases nonaromatized adducts are isolated. The reaction of isoquinoline IV-imine17,190 and phenanthridine iV-imine17,33 with dimethyl acetylenedicarboxylate gives tautomeric isomers of the primary adducts, e.g., 61. These IV-imines also react with iV-phenylmaleimide to give the primary 1 1 cycloadducts, e.g., 62.33,190 Of particular interest is the reaction of isoquinoline IV-imine with mesityl oxide which produces 63. This reaction involves disproportionation and elimination of methane from the primary adduct.17... 

Brooke G, Drury C (1994) PartiaUy fluorinated heterocycUc compounds. Part 30. CycUsation reactions of Uthium l,3,4,5,7,8-hexafluoro-6-isoquinoline-thiolate and Uthium 2,3,5,6,7,8-hexa-fluoro-4-quinolinethiolate with dimethyl acetylenedicarboxylate. J Fluorine Chem 67 143-147... 

A simple preparation of electron-poor 2-azadienes and the preliminary study of their ability to participate in [4 + 2] cycloadditions was done almost simultaneously by out group (87CC1195) (Scheme 49). The preparation of 2-azadienes 212 with two appended methoxycarbonyl groups was achieved, in a multigram scale and in nearly quantitative yield, by the insertion reaction of N- trimethylsilyl imines 210 into the carbon—carbon triple bond of dimethyl acetylenedicarboxylate to give 211 followed by protodesilylation with CsF/MeOH. Azadienes 212 underwent at room temperature inverse-electron demand [4 + 2] cycloaddition with cyclic enamines to give exclusively exo-cycloadducts 213 in 82-95% yield. Acid hydrolysis of them resulted in their aromatization to yield 2-pyrindine (n = 1] and isoquinoline (n = 2) derivatives 214. 

The anion (26) of the isoquinoline Reissert compound (2) has been used in a Michael-type reaction. Thus, reaction of 26, generated with phenyllithium, with ethyl cinnamate and substituted cinnamates give rise to 63, dimethyl acetylenedicarboxylate yields 64, and 2- and 4-vinylpyridines give rise to 65. Use of cinnamonitrile in this sequence leads to the isolation of 66. The enol ester, vinyl acetate reacts with the isoquinoline Reissert compound in aqueous sodium hydroxide containing TEBA chloride to surprisingly give 67. ... 

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