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Methods have been devised to generate 1H-1,3-diaza-1,3-butadienes bearing a leaving group at position-4 in latent, masked, and unprotected forms. A hallmark of these azadienes is that they undergo thermal [4π + 2π] cycloaddition reactions with electron deficient acetylenes to give adducts which are aromatized to pyrimidine derivatives under the reaction conditions. Thus, 1-(methoxycarbonyl)-3-acylamidines 17 on heating in solution are converted in situ into the 1,3-diaza-1,3-dienes 18 and/or 19 which react with dimethyl acetylenedicarboxylate (DMAD) to produce the pyrimidines 20. The 1-Boc-1,3-diaza-1,3-dienes 24 are masked forms of the 1H-dienes inasmuch as they react with DMAD under relatively mild conditions to give the dihydropyrimidine adducts 25, which are easily detectable by 1H NMR spectroscopy, and which aromatize to pyrimidines 26 at higher temperatures. The 4-methylthio compounds 31 and 33, and the 2-(trichloromethyl) compounds 37, are isolable, relatively stable, 1H-1,3-diaza-1,3-butadienes. These easily prepared compounds react with electron deficient acetylenes under mild conditions to provide the pyrimidines 20, 34, and 38, respectively, in fair to excellent yields. The 2-(trichloromethyl)pyrimidines 38 are very useful precursors of a wide variety of other 2-substituted pyrimidines 46-52.

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, 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.

Parallel reaction conditions employing tetrabutylammonium iodide (19.4 g, 52.5 mmol, Aldrich) as the halide source for 16 h afforded the l-iodo-4-pentanol (3)5 in 32% yield after chromatography (silica gel, eluted with ether). Standard treatment of this alcohol (16 h, 21 °C) with acetic anhydride (15 mL) and pyridine (3 mL) with a catalytic amount of 4-(dimethylamino)pyridine (15 mg) afforded the acetate 4; 3.26 g (80%); IR (film) 1735 (0=0) cm'1; NMR (CDC13) 1.20 (d, 3 H, J = 6 Hz, CflgCHOAc), 1.35-2.05 (m, 4 H, CH2CH2), 2.05 (s, 3 H, CH3C=0), 3.21 (t, 2 H, J = 7 Hz, CH2I), 4.85 (m, 1 H, HCOAc).Reactioin of 2-methyltetrahydrofuran with anhydrous lithium bromide and boron trifluoride etherate in dichloromethane for 44 h gave 5 and 8 in approximately equal amounts on the basis of the integration of the methyl doublets at 1.29 and 1.40 in the NMR spectrum.1 -Acetoxy-4-bromopentane (9). Acetyl bromide (12.3 g, 100 mmol) in a pressure-equalizing dropping funnel was added dropwise over 20 min to a solution of 2-methyltetrahydrofuran (10.3 g, 120 mmol) containing zinc chloride (4 mg) maintained at 0 °C by an external ice bath. After addition was complete the ice bath was removed, the reaction stirred at 21 °C for 0.5 h and refluxed for 2.5 h. The reaction mixture was cooled, diluted with ether (130 mL), washed with 5% aqueous sodium bicarbonate solution, water, and brine, dried and the product purified by distillation to give 9: 19.6 g (93%); bp 65-68 °C (2.5 mm) [lit.12 bp 60 °C (0.01 mm)]; NMR (CDC13) 1.73 (d, 3 H, J = 6 Hz, CtfgCHBr), 1.7-1.9 (m, 4 H, CH2CH2), 2.00 (s, 3 H, CH3OC=0), 4.01 (m, 3 H, CHBr, CH2OAc). A weak doublet at 1.23 indicated the presence of ~10% of the positional isomer 6.

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