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Indoles - Sundberg R.J.

Sundberg R.J. Indoles - Academic press, 1996. - 95 p.
ISBN 0-12-676945-1
Download (direct link): indoles1996.djvu
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7.1 FISCHER INDOLE SYNTHESIS
69
6 Б. J. Corey and A. Tramontane», J. Am. Chem. Soc. 103, 5599 < 1981).
7 S. B. Rajur, A, Y. Merwade and L. D. Basanagoudar, Synth. Commun. 22, 421 (1992).
8. K. Andersen, J. Perregaard, J. Arnt, J. B. Nielsen and M. Begtrup, J. Med. Chem. 35 4823
(1992).
9, L. Bretherick, K. Gaimster and W. R. Wragg, J. Chem. Soc. 2919 (1961).
10. T. A. N. Trinh and M. Lamant, Butf. Soc. Chim. Fr. 361 (1987).
7.1.7 Oxindoles from A/-acylphenylhydrazines
Oxindoles can be prepared from N,p-acylphenylhydrazines by a reaction which is analogous to the Fischer cyclization. This is known as the Brunner reaction. The reaction is typically conducted under strongly basic conditions. For example, heating N-phenylcyclopentanecarbonylhydrazide with CaO gives a 70% yield of spiro-cyclopentane oxindole[l].
Calcium hydride has also been used as the base[2,3]. Л comparison of the effect of metal cations indicated that yields increase in the order K+ < Na+ < Li+ and a procedure in which rc-BuLi serves as the base has been developed [4].
Procedure
3,3,7-Trimethyloxindole[3]
Ground, predried CaH (11.0 g, 0.26 mol) was added to a mixture of N-(2-mcthylphenyl)-2-methylpropanoylhydrazide (25.0 g, 0.13 mol) in tetralin (500ml). The mixture was slowly heated over 2h to about 200°C and kept at that temperature for 30 min. The reaction mixture was slowly cooled to room temperature and a solution of aq. methanol (100 ml, 50% by vol) was carefully added at 0-5°C. After H, evolution ceased, the pH was adjusted to 1 with cone. HCl and the mixture heated at reflux for 1 h. Then 3 N NaOH was added to bring the pH to 5. A precipitate formed and was collected and dried to give
20.1 g (89% yield) оГ the product.
References
1. R. F. Moore and S. G. P. Plant. J. Chem. Soc. 3475 (1951).
2. D. W. Robertson, J. H. Krushinski, G. D. Pollock, H. Wilson, R. F. Kauffman and J. S. Hayes. J. Med. Chem. 30, 824 (1987).
3. A. R. Lee. W.-H. Huang. T.-L. Lin, К -M. Shih, H,-F. Lee and C.-I. Lin, J. Hetereocvcl. Chem. 32,1(1995).
4. J. Wolff and M. Taddei, Tetrahedron 42, 4267 (1986).
(7.13)
70
7 CATEGORY Пае CYCLIZATIONS
7.2 INDOLES FROM W-ARYL-O-HYDROXYLAMINES
The oxygen analogue of the Fischer cyclization requires the formation of
O-vinyl derivatives of N-arylhydroxylarnines. These are readily converted to indoles but are less readily accessible than the arylhydrazones used for the Fischer cyclization.
^Y-CH2CH=0
0—Мносн*нг — — [1^Ц> (7.14)
H
One route to O-vinyl derivatives involves LiPdCl4-catalysed exchange with vinyl acetate[l]. Rearrangement and cyclization occur concurrently to give
1-acylindoles.
Li2PdCi4
<ГЛ-мон + сн2=сно2ссн3 -- (7-15)
’ ' P С
CR
О' O'
,CR
Addition of arylhydroxylamines to electrophilic allenes such as methyl propadienoate or l-methancsulfonyl-l,2-propadiene is another route to 0-vinyl derivatives[2]. The addition step is carried out by forming the salt of the hydroxylamine using NaH and the addition is catalysed with Li02CCF3. The intermediate adducts are cyclized by warming in formic acid. Yields are typically 80% or better.
I
R
TV-Substituted arylhydroxylamines add to methyl propynoate and rearrangement occurs to give indole-3-carboxylate esters[3], With unsubstituted
7.3 ГНН CiASSMAN SYNTHESIS
71
arylhydroxylamines addition occurs a second time and the products are ЛЧР-carbomethoxyvinyl)indoles[4],
OO2CH3
<f^)_NOH + hcecco2ch3 (7.17)
R 1
R
R = CH2Ph, СОгСНгР!!
Procedure
1 -Benzyl-3-methyl 6-methoxyindole-1,3-dicarboxylate[3]
iV-Benzyloxycarbonyl-3-methoxyphenylhydroxylamine(1.84 g, 6.74 mmol) and methyl propynoate (1.2ml, 13.5 mmol) were dissolved in dry CH2C12 (20ml). N-Methylmorpholine (0.74 ml, 6.73 mmol) was added at room temperature. The temperature of the solution rose to 40°C. Stirring was continued for 1 h and the solvent removed. The product was purified by elution through silica gel using 1:1 CH2Cl2-hexane. The product was recrystallizcd from methanol. The yield was 1.51 g (66%).
References
1. P. Martin, Heir. С him. Acta 67. 1647 (1984).
2. S. Blechert, Hek. Chini. Acta 68, 1835 (1985).
3. M. Toyota and K. Fukumoto, lleterocycles, 31, 1431 (1990); M. Toyota and K. Fukumoto, J. Chem. Soc., Perkin Trans 1 547 (1992).
4. J. R. H\vu, H- V. Patel, R. J. Lin and M O. Gray, J. Org. Chem. 59, 1577 (1994).
7.3 REARRANGEMENT OF ANIUN0SULF0NIUM YLIDES-THE GASSMAN SYNTHESIS
Gassman and co-workers developed a synthetic route from anilines to indoles and oxindoles which involves [2,3]-sigmatropic rearrangement of anilinosul-fonium ylides. These can be prepared from N-chloroanilines and a-thiomcthyl-ketones or from an aniline and a chlorosulfonium salt[ 1]. The latter sequence is preferable for anilines with ER substituents. Rearrangement and cyclization occurs on treatment of the anilinosulfonium salts with Et3N. The initial cyclization product is a 3-(methylthio)indole and these can be desulfurizcd with Raney nickel. Use of 2-(methylthio)acetaldehyde generates 2,3-unsubstituted indoles after desulfurization[2]. Treatment of 3-methylthioindoles with tri-fluoroacetic acid/thiosalicylic acid is a possible alternative to Raney nickel for desulfurization[3].
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