Pyrrole, 1- 2-methoxycarbonyl

Methoxycarbonyl)-7-methyl-l-(phenylsulfonyl)- 5-trimethylsilylindole 7-Methyl-l-phenylsulfonyi-l,5-dihydropyrano[3,4-b]pyrrol-5-one ethyl 3-trimethyIsilyIpropynoate 53 [1]... 

The reactivity sequence furan > tellurophene > selenophene > thiophene is thus the same for all three reactions and is in the reverse order of the aromaticities of the ring systems assessed by a number of different criteria. The relative rate for the trifluoroacetylation of pyrrole is 5.3 x lo . It is interesting to note that AT-methylpyrrole is approximately twice as reactive to trifluoroacetylation as pyrrole itself. The enhanced reactivity of pyrrole compared with the other monocyclic systems is also demonstrated by the relative rates of bromination of the 2-methoxycarbonyl derivatives, which gave the reactivity sequence pyrrole>furan > selenophene > thiophene, and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3] (35) with a further selection of heteroaromatic substrates (Scheme 5). The comparative rates of reaction from this substitution were 2-methylindole == AT-methylindole>indole > pyrrole > furan > thiophene (73CC540). 

Frontier orbital theory predicts that electrophilic substitution of pyrroles with soft electrophiles will be frontier controlled and occur at the 2-position, whereas electrophilic substitution with hard electrophiles will be charge controlled and occur at the 3-position. These predictions may be illustrated by the substitution behaviour of 1-benzenesulfonylpyr-role. Nitration and Friedel-Crafts acylation of this substrate occurs at the 3-position, whereas the softer electrophiles generated in the Mannich reaction (R2N=CH2), in formylation under Vilsmeier conditions (R2N=CHC1) or in formylation with dichloromethyl methyl ether and aluminum chloride (MeO=CHCl) effect substitution mainly in the 2-position (81TL4899, 81TL4901). Formylation of 2-methoxycarbonyl-l-methylpyrrole with... 

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. 

Halide substituted isoxazolines 371a-f gave bicyclic dihydropyridones 374 after rearrangement. Methoxycarbonyl substituted isoxazolines 371g-k gave the lactams 375, whereas carbonyl substituted isoxazolines 373a-e gave pyrroles 376 (Scheme 51). 

Pyrrolizin-3-ones may also be obtained by FVP of 3-(pyrrol-2-yl)propenoate esters such as 62, 69, and 74. Also, benzo-annulated pyrrolizinone 17 was obtained by FVP of 2-(tf-methoxycarbonyl phenyl (pyrrole <1999J(P1)2047>. FVP of alcohols 77, 78, and 79 led to 3//-pyrrolyzine derivatives 1, 192, and 193, respectively, in good yields (66-95%). These transformations proceed by elimination of water and subsequent electrocyclization of the in situ-generated cumulene (Scheme 44) <1999J(P1)2049>. 

The reaction of alkynyllithium compounds with alkoxycarbene tungsten complexes leads to anionic propargyl tungsten complexes (Figure 2.33 see also Figure 3.9). These intermediates are stable at low temperatures and react upon Lewis acid catalysis with aldehydes or A -sulfonyl imines to yield five-membered heterocycles [280]. Oxidative methoxycarbonylation [375] of the intermediate vinyl tungsten complex, followed by elimination of methanol leads to pyrroles or furanes (Figure 2.33 Entry 6, Table 2.22). 

Ring contraction with desulfurization occurs when the 4//-l,3-thiazines 131 are reacted with potassium /-butoxide (Scheme 7) <2004TL5913>. The bis(methoxycarbonyl)pyrroles 132 are not isolated but instead give the 4-oxo, 5 dihydro-2//-pyrrolo[3,4-c]quinolines 133 and 134. 

The reactions of methyl 2-formyl-677 or 6-substituted furo[2,3-. ]pyrrole-5-carboxylates 31d-f or 154 <1997MOL69, 1999CCC1135> with malononitrile, methyl cyanoacetate, and 2-furylacetonitrile, respectively, afforded the corresponding methyl 2-(2,2-dicyanovinyl)-677- or 6-substituted furo[2,3-. ]pyrrole-5-carboxylates 294a-d, methyl 2-[2-cyano-2-(methoxycarbonyl)vinyl]-677- or 6-substituted furo[2,3-. ]pyrrole 5-carboxylates 295a-d, and methyl... 

The monosubstitution products of the Friedel-Crafts reaction and of the nitration reaction have been interrelated to show that the substituent group is introduced at the same position in each case. A further correlation with the adduct (Id) from indolizine and methyl propiolate provides evidence that this is the 1-position as predicted.56 Acylation of 2-methoxycarbonyl-3-phenylcycl[3,2,2]azine (Is) takes place in the pyrrole part of the molecule.51... 

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