Pyrroles reaction with acetylenedicarboxylic

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>. 

The reactions of pyrroles with dimethyl acetylenedicarboxylate (DMAD) have been extensively investigated. In the presence of a proton donor the Michael adducts (125) and (126) are formed. However, under aprotic conditions the reversible formation of the 1 1 Diels-Alder adduct (127) is an important reaction. In the case of the adduct from 1-methylpyrrole, reaction with a further molecule of DMAD can occur to give a dihydroindole (Scheme 48) (82H(19)1915). 

A different mode of cycloaddition occurs with 7-azabicyclo[2.2.1]-heptadiene derivatives, in which the nucleophilicity of the nitrogen atom determines the point of attachment of the electrophilic dienophile. The addition depicted in 87, which may occur in two steps via a zwitterionic intermediate rather than by a concerted mechanism, accounts for the structures (88) of 1 2 adducts obtained with A-methyl- or A-benzyl-pyrrole and dimethyl acetylenedicarboxylate. At a higher temperature the reaction with A-methylpyrrole also afforded the indole tetraester... 

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). 

A mixture of 2-vinyl- 642 and ( ,Z)-2,5-divinyl- 643 pyrrolo[3,2- ]pyrroles was obtained in the reaction of pyrrolo[3,2- ]pyrrole 641 with an excess of dimethyl acetylenedicarboxylate (DMAD). A mixture of the (E)- and (Z)-isomers of the divinylpyrrole 643 (in 24% and 47% yields, respectively) can also be prepared by the addition of the monoadduct 642 to dimethyl acetylenedicarboxylate under the same conditions (Equation 153) <1998H(48)433>. 

The formation of pyrrole derivatives has been reported earlier. The triazoline (392) was converted by heating at its melting point into the 4-oxazoline (393) which in turn gives the 2,5-dihydropyrrole (394) on reaction with ethyl acetylenedicarboxylate (70CR(C)(27i)9S8). 

Oxadiazoles. - 1,2,3-Oxadiazoles. Irradiation of the sydnone (466) affords the betaine iV-oxide (467) in low yield " the reaction with dimethyl acetylenedicarboxylate gives a mixture of the pyrrole (468) and the oxazinone (469) both originate from the intermediate cyclo-adduct... 

This reaction can also be regarded as a Michael addition of pyrrole to maleic anhydride. Some substituted pyrroles, however, undergo a [4+2] cycloaddition with acetylene dienophiles, e.g. l-(ethoxycar-bonyl)pyrrole with acetylenedicarboxylic ester [37]. 

Diels-Alder addition product, from 1-methylpyrrole and maleic anhydride 2 is a further example of this sort of reaction. 2-Methylpyrrole behaves similarly, but the initial product (10) from pyrrole is obtained in small yield because it reacts further (p. 88). Pyrroles such as 2-methyl-, 1,2-dimethyl-and 2,4-dimethyl-pyrrole undergo similar Michael additions with methyl acetylenedicarboxylate s, 254 jn the third instance two molecules of the pyrrole reacting to form (11). 1-Methoxycarbonylpyrrole reacts at the 2-position with acetylene dicarboxylic acid254 as well as giving a Diels-Alder type of product (p. 82). With the same acid, ethyl 3,5-dimethylpyrrole-2-carboxylate undergoes Michael addition at the vacant jS-position giving (12). Other examples of reactions with dienophiles are discussed below... 

The formation from pyrroles and dienophiles of substances which are the results of Michael addition has been mentioned (p. 70). In some cases Diels-Alder addition does occur. Thus, with methyl acetylenedicarboxylate, methyl pyrrole-1-carboxylate gives (50), formed by elimination of acetylene from the initial Diels-Alder product . From 1-methylpyrrole, (51) is obtained , formed from the initial Diels-Alder product by reaction with a second molecule of methyl acetylenedicarboxylate . 1-Benzylpyrrole... 

K. Ando, M. Kankake, T. Suzuki, H. Takayama, New building blocks, 3,5-dihydro-lH-thieno[3,4-c]pyrrole-2,2-dioxides preparation and their EHels-Alder reaction with dimethyl acetylenedicarboxylate, J. Chem. Soc. Chem. Commun. (1992) 1100-1102. 

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