Sulfur-assisted synthesis of functionalized carbazoles.

Murase, Masayuki; Hosaka, Toshihiro; Koike, T.; Tobinaga, Seisho

doi:10.1248/cpb.37.1999

Cited by 21 publications

(12 citation statements)

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“…Although N ‐H‐acetylpyrrole 38 was a crystalline solid that could be recrystallized for facile purification, N ‐methylacetylpyrrole 39 was a liquid that on TLC showed several closely spotting impurities; two fractional vacuum distillations gave 39 in a purity of approximately 7:1 by mass. 2‐Acetyl‐5‐methylthiopyrroles 38 and 39 were then treated with Lawesson's reagent , giving N ‐H‐ and N ‐methyl‐ 2‐acetyl‐5‐methylthiopyrroles 40 and 41 .…”

Section: Resultsmentioning

confidence: 99%

“…A mixture of the vinylpyrroles 42 and 43 [2.919 mmol, generated freshly from 2‐methylthio‐5‐thioacetyl‐1 H ‐pyrrole 40 (500 mg), approximately 1:2 42 : 43 by mass ], and the maleimide 16 (1.1 equiv) in chloroform was stirred at RT for 3 d and then refluxed for 5 h. The solvent was removed using a rotating evaporator. The crude adduct was purified by MPLC using ethyl acetate/hexanes as eluent, followed by recrystallization from methylene chloride/petroleum ether, giving 44 (405 mg, 38%) as a white powder: mp 136–137°C; 1 H NMR (300 MHz, CDCl 3 , δ) 7.25 (d, J = 8.7 Hz, 2H, Ph), 7.19 (d, J = 8.7 Hz, 2H, Ph), 6.50 (s, 1H, 7‐H), 4.13 (d, J = 9.3 Hz, 1H, 8bα‐H), 4.07 (dd, J = 3.9, 2.4 Hz, 1H, 5α‐H), 3.65 (s, 3H, 6‐Me), 3.33 (ddd, J = 9.2, 7.1, 2.0 Hz, 1H, 3aα‐H), 3.03 (ddd, J = 14.6, 2.0, 2.0 Hz, 1H, 4β‐H), 2.65 (q, J = 7.6 Hz, 2H, C H 2 CH 3 ), 2.27 (s, 3H, MeS), 2.18 (s, 3H, MeS), 2.16 (ddd, J = 14.7, 6.9, 3.9 Hz, 1H, 4α‐H), 1.22 (t, J = 7.7 Hz, 3H, CH 2 C H 3 ); 13 C NMR (75 MHz, CDCl 3 , δ) 179.5, 177.3, 145.2, 130.7, 129.9, 129.2, 127.0, 125.9, 114.6, 112.7, 39.6, 38.4, 38.2, 30.5, 29.3, 26.4, 21.4, 16.13, 16.11; IR (KBr, cm −1 ) 2965(m), 2916(m), 1775(w), 1705(s), 1514(m), 1444(m), 1432(m), 1395(m), 1347(w), 1309(w), 1296(w), 1258(w), 1216(m), 1191(m), 1139(w), 1109(w), 960(w), 870(w), 837(w), 817(m), 789(w), 761(w); HRMS m/z (M + Na + ) calcd 423.1172, found 423.1187.…”

Section: Methodsmentioning

confidence: 99%

“…Murase et al . showed that 3‐(1‐(methylthio)vinyl)indoles and 3‐(1‐(benzylthio)vinyl)indoles underwent [4 + 2] cycloadditions with dimethyl acetylenedicarboxylate (DMAD) in 67 and 70% yields, respectively. In the only example found of Diels–Alder reactions of vinylpyrroles having an alkylthio‐substituted vinyl group, Murase et al .…”

Section: Introductionmentioning

confidence: 99%

“…Diels-Alder reactions of sulfonyl-substituted [20,21], sulfinyl-substituted [22], and sulfanyl-substituted [21,23] dienes are known, although none of the examples found involved removal of the sulfur group after the Diels-Alder reaction. Murase et al [24] showed that 3-(1-(methylthio)vinyl)indoles and 3-(1-(benzylthio)vinyl) indoles underwent [4 + 2] cycloadditions with dimethyl acetylenedicarboxylate (DMAD) in 67 and 70% yields, respectively. In the only example found of Diels-Alder reactions of vinylpyrroles having an alkylthio-substituted vinyl group, Murase et al [25] showed that the corresponding 3-(1-benzylthio)vinylpyrrole gave the Diels-Alder adduct with DMAD in 31% yield; surprisingly, the yields we achieved in our work with Diels-Alder reactions of the comparatively deactivated N-toluenesulfonyl-3-vinylpyrrole with maleimides were much higher [7].…”

Section: Introductionmentioning

confidence: 99%

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

Noland

Lanzatella

Dickson

et al. 2013

J. Heterocyclic Chem.

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in Wiley InterScience (www.interscience.wiley.com).Variously substituted 2-vinylpyrroles underwent an endo-addition [4þ2] cycloaddition reaction with maleimides followed by a spontaneous highly diastereoselective (93-98% de) isomerization to give tetrahydroindoles in moderate to excellent yield. Treatment with activated MnO 2 in refluxing toluene provided the corresponding indoles in moderate to good yield. This highly convergent methodology for formation of indoles is versatile and the starting materials are conveniently prepared.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Noland

Lanzatella

Dickson

et al. 2013

J. Heterocyclic Chem.

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“…mp 199-201°C (ether-benzene). 14: 1 Nor-methyl-9,10-dimethoxycarbonyldehydrochuangxinmycin Methyl Ester (16) POCl 3 (0.28 ml) was slowly added to dry DMF (0.9 ml) at 0°C, with stirring under nitrogen. After 10 min, a solution of 11c (480 mg, 1.4 mmol) in THF (0.5 ml) was added, and the mixture was stirred at 35°C for 1 h. The reaction mixture was poured into ice-water, 40% aq.…”

Section: 10-dimethoxycarbonyldehydrochuangxinmycin Methyl Ester (14)mentioning

confidence: 99%

Improved Preparation of Sulfur Substituted 3-Vinylpyrrole and Its Application to the Syntheses of Chuangxinmycin Derivatives.

Yoshida

Ito

Ibusuki

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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The Diels-Alder (D-A) reaction is one of the most useful reactions in synthetic organic chemistry. Recently, we reported that thiocarbonyl compounds 2, 4, and 6 yielded dienes 3, 5, and 7, respectively, through alkylation reactions, and these dienes underwent Diels-Alder reaction with appropriate dienophiles to give functionalized carbazoles, indoles, and benzene derivatives.1-3) Previously, we found that 4-thioxo-4,5,6,7-tetrahydroindole 8, having a thioenaminone moiety, gave dehydrochuangxinmycin through alkylation. 4)We also found that the cycloaddition reaction of N-methyl-3-vinylpyrrole 5 proceeded smoothly, whereas the NH congener 9 gave no cycloaddition product. This may be due to the lability of vinylpyrrole 10, and the result was not investigated further.This paper describes an improved synthesis of sulfur substituted 3-vinylpyrroles 10 and their application to the syntheses of chuangxinmycin having various substituents. In 1978, E. J. Cory et al. reported the utility of intramolecular Diels-Alder reaction using propylene oxide as a hydrogen chloride scavenger in the synthesis of gibberellic acid.5) The application of propylene oxide as a scavenger prompted us to examine its use in the preparation of 3-vinylpyrrole 10 from 3-thioacetylpyrrole 9 and alkyl halide. A preliminary study was done on the reaction of 10a, generated in situ by the reaction of 3-thioacetylpyrrole 9 with methyl iodide in the presence of a large excess of propylene oxide, with dimethyl acetylenedicarboxylate (DMAD) in tetrahydrofuran (THF). The indole 11a was indeed obtained in 20% overall yield. Similarly, the reactions of 10b and 10c, generated in situ with benzyl bromide and methyl bromoacetate, with DMAD, gave the indoles 11b and 11c, in 17.2 and 27.3% yields respectively. Figure 2 proposes a possible mechanism for the generation of dienes 10. Reaction of the diene 10c with Nmethylmaleimide at 110°C for 8 h, followed by treatment with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) for 30 min, gave the indole 12a in 27.3% yield. Similarly, the reaction of the diene 10c with 3,4-dibromo-N-methylmaleimide in THF at room temperature for 8 h, followed by direct in situ oxidation, gave 12a in 36.5% yield.In general, the cycloaddition reaction of vinylpyrroles 10 with dienophiles were carried out in a fused glass tube at 100°C under nitrogen for approximately 8 h. The results are summarized in Table 1. The indoles 11c and 12a are the key intermediates in the syntheses of substituted chuangxinmycin derivatives.Synthesis of 7,8-Disubstituted Chuangxinmycin Derivatives Chuangxinmycin 1, isolated from the microorganism Actinoplanes tsinanensis n. sp. of China, 6) is an antibiotic alkaloid bearing a sulfur substituent at the 4-position of the indole nucleus. This compound is known to be active against a variety of Gram-positive and Gram-negative bacteria and is particularly effective in the treatment of Escherichia coli infections. 7)Total synthesis of 1 has already been reported by several groups.8) We also have reported two routes of fo...

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