Methyl 6//-furo pyrrole-5-carboxylate

The differences in aromaticity follow the results of theoretical analyses on the acidity of the NH proton of the pyrrole fragment of furo[ ]pyrroles <2000PJC207> and are nicely reflected in the observed stability of both systems. The total energy difference between methyl 4f/-furo[3,2- ]pyrrole-5-carboxylate 8a and methyl 6f/-furo[2,3- ]pyr-role-5-carboxylate 31a is rather small (—7.2 kj mol ) indicating the higher stability of the former system. However, if the increase of energy of the appropriate anions is compared (relative to the parent molecules), then it indicates that formation of 67/-furo[2,3-7]pyrrole-5-carboxylate anion is much easier (by —22.5 kJ mol ) than formation of 4//-furo[3,2- ]pyrrole-5-carboxylate anion. 

The formylation of methyl furo[2,3-/)]pyrrole-5-carboxylate 31a and its variously iV-substituted derivatives 31b, 31c, and 153 has been studied and 31d-f, and 154 were obtained (Equation 2) <1997MOL69, 1999CCC1135>. 

The condensation of furo[3,2- ]pyrrole-type aldehydes 8g and 265-267 with hippuric acid was carried out in dry acetic anhydride catalyzed by potassium acetate as is shown in Scheme 26. The product methyl and ethyl 2-[( )-(5-oxo-2-phenyl-l,3-oxazol-5(4//)-ylidene)methyl]furo[3,2- ]pyrrol-5-carboxylates 268a-d were obtained. The course of the reaction was compared with the reaction of 5-arylated furan-2-carbaldehydes with hippuric acid. It was found that the carbonyl group attached at G-2 of the fused system 8 is less reactive than the carbonyl group in 5-arylated furan-2-carbaldehydes in this reaction <2004MOL11>. The configuration of the carbon-carbon double bond was determined using two-dimensional (2-D) NMR spectroscopic measurements and confirmed the (E) configuration of the products. 

Fig. 13 6-Methyl-2-[( )-(oxo-2-phenyl-l,3-oxazol-5(47/-ylidene)methyl]furo[2,3-fc] pyrrole-5-carboxylate 233b, 6-methoxymethyl-2-[( )-(oxo-2-phenyl-l,3-oxazol-5(4//-ylidene) methyl] furo[2,3-fc]pyrrole-5-carboxylate 233d [22] 3-benzyl-2-[( )-2-[5-(methoxycarbonyl)-6-methoxymethylfuro[2,3-fe]pyrrol-2-yl]vinyl -l,3-benzotiazolium bromide 234 [23]...

The reactions of the methyl furo[2,3-6]pyrrole-5-carboxylate (153) or its 6-methyl derivative (154) with DMAD proceed via [4 -I- 2] cycloaddition at the a,a -positions of the furan ring, giving cycloadducts which by subsequent 1,5-sigmatropic rearrangement give trimethyl 5-hydroxyindole-2,6,7-tricarboxylate (155) or its 1-methyl derivative (156) <94UP 70i-0i>. 

Phase-transfer catalysis was found <1996CHEC-II(7)1> to be successful for N-substitution of the furo[3,2-/ ]pyrrole system. The reaction of 81a with methyl iodide or benzyl chloride gave 81b and 81c derivatives. Methyl 4-acetyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-3]pyrrole-5-carboxylate 82 was obtained by reacting 81a in boiling acetic anhydride (Scheme 6) <2005CEC311>. 

An attempt to introduce a bulky triphenylmethyl substituent at N-(y of methyl 677-furo[2,3-7]pyrrole-5-carboxylate 31a led to C-2 triphenylmethyl substitution giving the product 157, which with ethyl propynoate in acetonitrile gave the Michael addition product 158 <2000PJC207> (Scheme 16). 

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... 

Milkiewicz et al. <2003TL4257> prepared a series of novel tetrasubstituted furo[3,2-/ ]pyrroles from the methyl or ethyl 3-bromo-2-phenylfuro[3,2-3]pyrrole-5-carboxylate 336. The compounds 336 were subjected to a Suzuki coupling with 4-chlorophenylboronic acid to form 337, which was treated with a variety of alkylating agents to afford the corresponding esters 338. The esters were then saponified to acids 339 (Scheme 34). 

Methyl 2-[3-(trifluoromethyl)phenyl]-4/7-furo[3,2-4]pyrrole-5-carboxylate 81a was made by thermolysis of the corresponding methyl 2-azido-3- 5-[3-(trifluoromethyl)phenyl]-2-furyl propenoate 378, which was formed by condensation of 5-[3-(trifluoromethyl)phenyl]furan-2-carbaldehyde 377 with methyl azidoacetate under sodium meth-oxide catalysis (Scheme 40) <2006KGS825>. 

The 1,3-dipolar cycloadditions of ethyl 4//-furo[3,2-/>]pyrrole-5-carboxylate (8a) or its 4-methyl derivative (8f) (Equation (2)) with C-benzoyl-A-phenylnitrone and ACV-diphenylnitrone proceeded regiospecifically at positions 2 and 3 of the furan ring. During these reactions, exclusively endo cycloadducts were formed, because their transition states are stabilized by secondary orbital interactions <81CCC2421>. 

Oxiranylmethyl)furo[3,2-/)]pyrrole-5-carboxylate (272) with morpholine undergoes oxirane ring opening to form the. -substituted derivative of methyl 4-(3-amino-2-hydroxypropyl)furo[3,2-/>]pyrrole-5-carboxylate (273). Using pyrrolidine as nucleophile the fused aza-lactone (274) is formed (Scheme 18) <95UP 701-01). 

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