Pyrroles annulated

Pyrrolyl)-4,5-dihydroisoxazole derivatives 402 have been synthesized (Scheme 1.48) in good yields (66%-78%) by regioselective 1,3-dipolar cycloaddition of nitrile oxides to 1-phenylsulfony 1-1,3-dienes, followed by Barton-Zard pyrrole annulation using ethyl isocyanoacetate anion (444). 

Among early reported Pd-catalyzed reactions, the Mori-Ban indole synthesis has proven to be very useful for pyrrole annulation. In 1977, based on their success of nickel-catalyzed indole synthesis from 2-chloro-fV-allylaniline, the group led by Mori and Ban disclosed Pd-catalyzed intramolecular reactions of aryl halides with pendant olefins [122]. Compound 102, easily prepared from 2-bromo-lV-acetylaniline and methyl bromocrotonate, was adopted as the cyclization precursor. Treatment of 102 with Pd(OAc)2 (2 mol%), Ph3P (4 mol%) and NaHCQ3... 

The mechanism for the Mori-Ban indole formation is representative of many Pd-catalyzed pyrrole annulation processes [123], Reduction of Pd(OAc)2 by PPh3 generates Pd(0) species accompanied by triphenylphosphine oxide and acetic anhydride. 

To make tryptophan analogs, Gronowitz and coworkers conducted a pyrrole annulation from an aminoiodopyrimidine utilizing the Larock indole synthesis conditions (see Section 1.10.) [80]. They prepared heterocondensed pyrrole 115 by treating 4-amino-5-iodopyrimidine 114 with trimethylsilyl propargyl alcohol under the influence of a palladium catalyst The regiochemical outcome was governed by steric effects. 

Our interest in expanding the acylative pyrrole annulation approach to additional heterocyclic systems has led to an efficient synthesis of pyrrolo[3,2-c]pyridin-2-ones and pyrido[3,4-6]pyrrolizidin-l-ones starting from 4-chloro-N-benzyl-2(l//)-pyridinone and amino acid salts.811 Over the years pyrrolo[3,2-c]pyridines (5-azaindoles)41 have been of interest for applications as elements in new drug design, nucleotide analogues,42 and biochemical tools. However, available synthetic routes to multifunctionalized members from this class of heterocyclic structures are limited.41 43... 

The pyrrole annulation of 291 with different isocyano derivatives afforded the resin-bound products 292, which were released from the resin with 10% TFA leading to 293 (Scheme 67) <2004JC0142>. 

Dihydro-l/f-dipyrrolo[3,2-(> 2, 3 -t/]pyrrole (14a) and 4,7-dihydro-4/f-thieno[3,2-6]pyr-rolo[2,3- f]pyrrole (13) (Table 2) have also been elegantly synthesized employing pyrrole annulation techniques on suitable pyrrolopyrrole (126) and thienopyrrole (129) derivatives as substrates via intermediates (127), (128) and (130), (131) respectively (Schemes 9 and 10) <89TL1655>. 

Pyrroles annulated with various kinds of polycyclic aromatic compounds such as the pyrrolo benzothiadiazole (578) have been claimed to be good precursors for polypyrroles. The polymers derived from (578) have a lowered band gap and interesting properties such as the high stability of the cation radicals formed by electrochemical oxidation. They also show ESR signals which are not affected after storage at room temperature for long periods of time in a laboratory atmosphere, <94CC1019>. 

The pyrrole analogue of poly(isothianaphtene), poly(A-methylisoindole) (69), was electropolymerized [313] but the optical gap (431 nm, 2.88 eV) is not lower than that of polypyrrole due to the steric constraints (plane distortion) caused by V-substitution. At difference a significant lowering (600 nm, 2.07 eV) was achieved with a polymer from pyrrole annulated with a naphthalene moiety (70) [314]. 

Scheme 38 Brpnsted acid-catalyzed synthesis of 1,2-pyrrole-annulated benzazepines through a redox-neutral domino reaction...

Trost, B.M. and E. Keinan. 1980. Pyrrole annulation onto aldehydes and ketones via palladium-catalyzed reactions. J Org Chem 45 (14) 2741—2746. 

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