Download (direct link):
Selective oxidations of 2-alkyl groups usually involve an initial attack at C3 followed by an allylic rearrangement which places the substituent at the ot-carbon of the C2 substituent. The overall pattern of ot-2C oxidation has been observed with several oxidants including oxygen and peroxysulfate[ll] but the most reliable reagent for preparative purposes is diiodinepentaox-ide, A few oxidations have also been reported using Mn(OAc), (Entry 13).
15.5 SELECTIVE OXIDATION OF SUBSTITUENTS
Methyl 4-oxo- 1,2,3,4-tetrahydrocarbazole-2-acetate
A solution of methyl l,2,3,4-tetrahydrocarbazole-2-acetate (5.94g) in THF (195ml) containing water (15ml) was cooled to СГС and DDQ (11.22 g) dissolved in dcoxygenated THF (75 ml) was added. The solution was maintained at 0°C for 2 h and then evaporated in vacuo. The residue was dissolved in EtOAc and washed thoroughly with aq. NaHCOs solution to remove dichlorodicyanohydroquinone. The EtOAc was then dried (MgS04) and evaporated to give methyl 4-oxo-1,2,3,4-tetrahydrocarbazole-2-acetate (5.23 g) in 85% yield.
Oxidation of cycloalkan[b]indoles with diiodinepentaoxide
I205 (400 mg 1.20 mmol) was added to a solution of a cycloalka[b]indole (1.00 mmol) in 80% aqueous THF (25 ml). The mixture was stirred at room temperature and the solvent removed in vacuo. The residue was extracted into EtOAc and the extract washed with water, 5% NaS2Oj, saturated NaHC03 and brine and dried over Na2S04. The solvent was evaporated and the residue purified by silica gel chromatography.
1 Y. Oikawa and O. Yonemitsu, J. Org. Chem. 42, 1213 (1977).
2. S. Nakatsuka, T. Masuda, K. Sakai and T. Goto, Tetrahedron Lett. 27, 5735 (1986).
3 J. Madalengoitia. PhD. Thesis (with T. L. Macdonald), University of Virginia. 1993.
4. B. Robinson, J. Heterocyclic Chem. 24, 1321 (1987).
5. P. Magnus, N. L. Sear, C. S. Kim and N. Vicker, J. Org. Chem. 57. 70 (1992).
6. M. Cain, R_ Mantei and J. M. Cook, J. Org. Chem. 47, 4933 (1982).
7. T. J. Hagen, K. Narayanan. J. Names and J. M. Cook, J. Org. Chem. 54, 2170 (1989).
8. M. Cain, O. Campos, F. Guzman and J. M. Cook. J. Am. Chem. Soc. 105, 907 (1983).
9. J. Gracia, N. Casamitjana, J. Bonjoch and J. Bosch, ./. Org. Chem. 59, 3939 (1994).
10. E. Leete, J. Am. Chem. Soc. 83, 3695 (1961).
15 SELECTIVE REDUCTION AND OXIDATION REACTIONS
11. M. Balon, M. Munoz, P. Guardado, J. Hidalgo and C. Carmona,./. Org. Chem. 58, 7469 (1993); C, Carmona. M. Balon, M. A. Munoz, P. Guardado and J. Hidalgo, J. Chem. Snc. Perkin Trans. 2 33! (1995).
12. K. Yoshida. J. Goto and Y. Ban, Chem. Pharm. Bull. 35, 4700 (1987).
13. Y. Ban. K. Yoshida, J. Goto and T. Oishi, J. Am. Chem. Soc. 103, 6990 (1981).
14. D. M. Ketcha, Q. Zhou and D. Grossie, Synth. Commun. 24, 565 (1994).
Synthetic Elaboration of Indole Derivatives using Cycloaddition Reactions
Two types of cycloaddition reactions have found application for the synthetic elaboration of indoles. One is Diels-Alder reactions of 2- and
3-vinylindoles which yield partially hydrogenated carbazoles. The second is cycloaddition reactions of 2,3-indolequinodimethane intermediates which also construct the carbazole framework. These reactions arc discussed in the following sections.
16.1 DIELS-ALDER REACTIONS OF 2- AND 3-VINYLINDOLES
While both 2- and 3-vinylindole have been synthesized and charaeterized[l,2], they arc quite reactive and susceptible to polymerization. This is also true for simple 1-alkyl derivatives which readily undergo acid-catalysed dimerization and polymerization. For this reason, exccpt for certain cases where in situ generation of the vinylindoles is practical, most synthetic applications of vinylindoles involve derivatives stabilized by EW-nitrogen substituents.
Most examples of Diels-Alder reactions reported for both 2-vinyl and
3-vinylindoles involve typical electrophilie dienophiles such as benzoquinone, Ar-phenylmaleimide and dimethyl acetylenedicarboxylate (see Table 16.1). These symmetrical dienophiles raise no issues of regioselectivity. While there are fewer examples of use of mono-substituted dienophiles, they appear to react
Diels -Alder reactions of 2-vinyl and 3-vinylindoles
Entry Indole substituents
A 2-Vinylindoles 1 2-Ethenyl
Yield (%) Ref.
CCH2CH3 46 CH3
В 3- Vinylindoles 6 3-Ethenyl
8 3-Ethenyl-l-(phenylsulfonyl) Benzoquinone
9 3-Ethen>l-l-(phenyIsulfonyl) jV-Phenylmaleimidc
16.1 D1ELS-ALDER REACTIONS OE 2- AND 3-VINYLINDOLES
in a prcdictablc fashion. 2-Vinylindoles appear to have the highest electron density at С3 of the indole ring. For 3-vinylindoles the P-carbon of the vinyl group has the highest FIOMO density and bonds to the more electron-poor P-carbon of the dienophile. While the initial adducts with exocyclic unsaturation are sometimes observed[5,6], in most cases an isomerization provides the rearomatized indole. Table 16.1 gives some examples of these reactions.