, 15 (1994) 1-(2-Bromobenzy1)-2-alkanesulfonylpyrroles (lc, 16) and 1-(4-bromobuty1)-2-methylsulfonfylpyrrols (8) undergo oxidative radical cyclization with partial or complete reductive desulfonylation to the pyrrolizidine derivatives 5 and 9 by an AIBN initiated reaction with tri-n-butyltin hydride. These cyclizations are suggested to proceed via a pseudo SRNl process involving radical addition to the a position of the pyrrole nucleus not bearing the sulfonyl group. Reductive removal of the alkylsulfonyl moiety is proposed to occur in a second process after completion of the oxidative radical cyclization. The site of the radical addition is supported by deuterium labelling studies. Consistent with the timing of the loss of the sulonyl group is that 2-alkysulfonylpyrroles 11 are reductively desulfonylated under the same conditions that effect the oxidative radical cyclizations. 15 (1994) Lorsqu'ils sont soumis une reaction initiee par 1'AIBN et l'hydrure de tri-n-butyletain, les 1-(2-bromobenzy1)-2-alcanesulfonylpyrroles (lc,ld) et les 1 -(4-bromobuty1)-2-m~thylsulfonylpyrroles (8) subissent une cyclisation radicalaire oxydante accompagnee d'une dCsulfonylation reductrice partielle ou complkte conduisant aux derives pyrrolizidine 5 et 9. I1 y a des indications i l'effet que ces cyclisations se produisent par le biais d'un processus pseudo S 1 impliquant une addition radicalaire sur la position RN, , . a du noyau du pyrrole ne portant pas le groupe sulfonyle. I1 est suggCrC que 1 elimination reductrice de la portion alkylsulfonyle se produit au cours d'un deuxikme processus, aprks la cyclisation radicalaire oxydante. Le site de l'addition radicalaire est en accord avec les etudes de marquage au deuterium. En accord avec la sequence des reactions, il faut noter que les 2-alkylsulfonylpyrroles (11) sont dCsulfonylCs d'une fa~on reductrice dans les conditions conduisant aux cyclisations radicalaires rkductrices.[Traduit par la redaction]Several years ago we embarked on a research program, the objective of which was to study the reactions of pyrroles with alkyl and aryl radicals. Although both radical addition and radical substitution reactions of pyrrole derivatives had been reported at that time (1, 2), only arylation had been systematically studied and was of preparative significance (see ref.

. Can. J. Chem. 60,2295Chem. 60, (1982. Several syntheses of the previously unknown 1,2-dihydro-3H-pyrrolo[l,2-a]pyrrole-l-carboxylic acid and various 5-and 6-substituted derivatives thereof have been devised. Some of these processes have been extended to the heretofore unreported 5,6,7,8-tetrahydropyrrolo[l,2-a]pyridine-8-carboxylic acid and 5,6,7,8-tetrahydro-9H-pyrrolo[l,2-a]azepine-9-carboxylic acid derivatives.Two new processes were developed for the conversion of pyrroles into the corresponding pyrrol-2-acetic acid esters. Both processes were based on the use of the readily available ethoxalylpyrrole derivatives as the starting material. One sequence involved saponification of the a-keto ester, followed by Wolff-Kishner reduction of the crude a-keto acid salt and subsequent esterification of the acetic acid derivative thus produced. The second synthesis commenced with reduction of the 2-ethoxalpyrrole with sodium borohydride to the a-hydroxy ester, which was further reduced to the acetic acid ester with an equimolar mixture of triphenylphosphine and triphenylphosphine diiodide.

No abstract

Acetic acid derivatives of tricyclic systems, such as 6,11-dihydro-11-oxodibenzo[b,e]thiepin, 4,10-dihydro-4-oxo-thieno[2,3-c][1]benzothiepin, dibenzo[b,f]thiepin, dibenz[b,f]oxepin, etc., were synthesized and assayed for antiinflammatory activity. One of the compounds, 6,11-dihydro-11-oxodibenzo[b,e]thiepin-3-acetic acid (52), was chosen for evaluation in man on the basis of high antiinflammatory activity in both short- and long-term animal assays and a low gastric irritation liability in rats and dogs.

Die Umsetzung des Bromids (I) mit dem [aus den Komponenten (II) und (III) gebildeten] Enamin (V) liefert das Pyrrol (IVa) (Hantzsche Pyrrolsynthese) ; Cyclisierung des aus (IVa) über das Mesylat (IVb) erhältlichen Iodids (IVc) gibt das Pyrrolopyrrol (VIa), das über die Stufen (VIb), (VIc) in den Ester (VIIa) bzw. dessen Verseifungsprodukt (VIIb) übergeführt wird.