Oxidative radical cyclization to pyrroles under reducing conditions. Reductive desulfonylation of α-sulfonylpyrroles with tri-n-butyltin hydride

Abstract

, 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.

Radical reactions with 3H-quinazolin-4-ones: synthesis of deoxyvasicinone, mackinazolinone, luotonin A, rutaecarpine and tryptanthrin

“…Radical cyclisation onto heteroarenes has been developed in recent years to considerable advantage for the synthesis of novel polycyclic heteroarenes. Examples of these cyclisations include: a. alkyl radicals onto pyrroles, 8,9 imidazoles, 8 pyrazoles, 10 indoles, 9,11, 12 1,2,3-triazoles, 13 pyridinium salts, 14 and quinolones; 15 b. acyl radicals onto pyrroles, 16 quinolines, 17 pyridines 18 and arenes; 19 c. aryl radicals onto indoles, 20,21 pyrroles, 9 pyridones, 22 and 5-amino-and 5-hydroxyuracils, 23 2-quinolones, 24 quinolines 25 and pyridines. 26 All of the above cyclisations are 'oxidative' i.e.…”

Access to Indoles via Diels-Alder Reactions of 5-Methylthio-2-vinylpyrroles with Maleimides

“…To synthesize bis‐methylthioated vinylpyrroles 42 and 43 , 2‐methylthiopyrroles 36 and 37 were first acetylated using a Vilsmeier–Haack reaction, giving 2‐acetyl‐5‐methylthiopyrroles 38 and 39 (Scheme ) ; Muchowski et al . have demonstrated that the 5‐methylthio group has a directing effect to give acylation exclusively at the 2‐position.…”

“…Crude N ‐methyl‐2‐methylthio‐5‐acetylpyrrole 39 (9.15 g, 54.064 mmol, included approximately 13% 2‐ and 3‐acetyl‐ N ‐methylpyrrole by mass) was dissolved in THF (250 mL). Lawesson's reagent (26.24 g, 64.877 mmol) was added, and the mixture was stirred at RT for 3 h, at which time TLC indicated complete consumption of the starting materials.…”

“…These include carboxylate and aldehyde groups , which are commonly removed, with aldehydes being oxidized first, by using high temperatures with strong base or acid, causing saponification followed by decarboxylation. Other electron‐withdrawing protective groups used are the more mildly cleavable sulfinyl and sulfonyl groups , using Raney nickel or radical‐induced reductive desulfonylation with Bu 3 SnH/AIBN , and the 2,4‐dinitrobenzenesulfinyl group, which can be removed by oxidation and then treatment with phenylthiol . Because these protecting groups would decrease the electron density of 2‐vinylpyrrole and would therefore likely cause an undesirable decrease in Diels–Alder reactivity, they did not suit our purposes.…”

Bu3SnH mediated oxidative radical cyclisations: synthesis of 6H-benzo[c]chromen-6-ones †

“…an oxidative process. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Most of the intermediate cyclised radicals are aromatic π-radicals which undergo rearomatisation by loss of hydrogen. The mechanism has been the subject of debate in the literature.…”