3- Methoxycarbonylpyrrole

The TV-protected pyrrole (212) can be palladated, but not lithiated, in the 3-position to give the stable complex (213) this is readily converted into the 3-methoxycarbonylpyrrole (214) (82JOM(234)l23). The use of palladium derivatives thus further increases the range of transformations made possible through the intermediacy of metallo groups. 

The N-protected pyrrole 457 can be palladated, but not lithiated, in the 3-position to give the stable complex 458 this is readily converted into the 3-methoxycarbonylpyrrole 459. 

Flash vacuum pyrolysis of 2-methoxycarbonylpyrrole (11) gives the ketene (12), characterized by IR absorption at 2110 cm. On warming to -100 to -90 °C the dimer (13) is formed (82CC360). Flash vacuum pyrolysis of indole-2-carboxylic acid (14) results in loss of water and the formation of a ketene (15) showing absorption at 2106 cm (82CC360). 

In the pyrrole series, ester groups a to nitrogen are more readily hydrolyzed by alkali, but those in a /3 position more readily by acid. A methoxycarbonyl group in the 2-positlon is meta directing thus bromination yields mainly 4-bromo-2-methoxycarbonylpyrrole. Free radical chlorination with f-butylhypochlorite gives the 5-chloro derivative. 

In connection with the above work, it should be noted that the 2-azabicyclo[3.1.0]hexene ring system can also be prepared by carbenoid addition to N-methoxycarbonylpyrrole. Thermally it rearranges to the dihydropyridine but the mechanistic pathway depends upon the substituent attached to the cyclopropane ring (equation 22) (72JA6495). 

The [4 + 2] cycloaddition reaction of 2- or 2,5-substituted iV-methoxycarbonylpyrroles with dimethyl acetylenedicarboxylate is accelerated tremendously by aluminum chloride (70CJC1472). The Diels-Alder cycloaddition is in fact complete in some cases within 30 min at 0 °C if five molar equivalents of A1C13 are utilized. On warming the reaction mixture to 40 °C, the 7-azabicyclo adduct (199) formed initially undergoes rearrangement to an Af-methoxycarbonyl-3-aminophthalate (200 Scheme 42). The overall scheme constitutes a valuable method for the construction of polysubstituted anilines. 

The Lewis acid-catalyzed reaction of the endoperoxide of 1-methoxycarbonylpyrrole with enol ethers presents an interesting route to 2-alkylpyrroles (Scheme 30) (79TL3477, 80H(14)102>. In the case of the reaction with l-(trimethylsilyloxy)buta-l,3-diene, the reaction provides a viable route to indole, which, with only slight modification, can also be employed in the synthesis of 4-substituted indoles <8lH(l6)959>. The endoperoxide reacts with 1-methylpyrrole to produce the l,l -disubstituted 2,2 -bipyrrole in low yield. 

Acetylation of pyrrole is difficult because if forms a 2 1 complex with stannic chloride (29CB226). Hence, under the conditions used for the other five-membered rings (i.e., acetic anhydride in the presence of one hundredth molar equivalent of stannic chloride or iodine), no reaction occurs, and only 20% acetylation is obtained if the molar proportion of the catalyst is reduced 10-fold. The effect of complex formation also shows up in the inhibition of stannic chloride-catalyzed acetylation of fu-ran or thiophene, on addition of pyrrole (67MI4). Catalyzed acetylation of 2-cyano-, 2-formyl-, or 2-methoxycarbonylpyrrole gives mainly 4-substitution (67CJC897) indicating that the catalyst must also be coordinated with the substrate l-methyl-3-nitropyrrole acetylates only in the 5-posi-tion (57CJC21). 

Several routes involve cycloreversions as final steps " each of the starting materials shown below is available from the cycloadduct (cf. 16.8) of benzyne and 1-methoxycarbonylpyrrole. 

A new route to tropane derivatives involving reaction of aao a -tetrabromoacetone with N-methoxycarbonylpyrrole and di-ironenneacarbonyl was described in Volume 5. 6,7-Dehydronortropinone derivatives (13) can also be obtained in good yields from aa -dibromoketones and pyrroles (or N-methylpyrroles) with copper and sodium iodide. ... 

The reaction of pyrrole with dichlorocarbene proceeds in part via a dichlorocyclo-propane intermediate, ring expansion of which leads to 3-chloropyridine." There are relatively few (section 14.1.2) reported isolable cyclopropane-containing adducts from pyrroles - l-methoxycarbonylpyrrole ° or N -acylpyrroles. 1-Methylpyrrole with ethoxycarbonylcarbene gives only substitution products. " ... 

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