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. 2009 Jan 7;50(1):63-65.
doi: 10.1016/j.tetlet.2008.10.086.

Regioselective Diels-Alder cycloadditions and other reactions of 4,5-, 5,6-, and 6,7-indole arynes

Neil Brown  1 , Diheng Luo, David Vandervelde, Shaorong Yang, Allen Brassfield, Keith R Buszek
Affiliations

Regioselective Diels-Alder cycloadditions and other reactions of 4,5-, 5,6-, and 6,7-indole arynes

Neil Brown et al. Tetrahedron Lett. .

Abstract

The regioselectivity of Diels-Alder cycloadditions of indole arynes (indolynes) at all three benzenoid positions was examined. Cycloadditions with the 4,5-and 5,6-indolynes, derived via metal-halogen exchange from the corresponding o-dibromo indoles, showed essentially no selectivity with 2-t-butylfuran. In contrast, the 6,7-indolyne displayed virtually complete preference for the more sterically congested cycloadduct. This same cycloadduct undergoes a facile acid-catalyzed rearrangement to afford the annulated enone, or alternatively, undergoes hydrolysis and oxidation in the presence of air to give the indolobenzoquinone. The 5,6-difluoroindoles show anomolous behavior and give either 5-fluoro-6,7-indolynes with n-BuLi in ether, or 5,6-indolynes with n-BuLi in toluene. We have also demonstrated that benzenoid indolynes can be easily and conveniently generated by the fluoride-induced decomposition of o-trimethylsilyl triflates.

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Figures

Figure 1
Figure 1
Benzenoid aryne systems.
Figure 2
Figure 2
Indole-containing complex natural products.
Scheme 1
Scheme 1
Regioselectivity of 4,5- and 5,6-indolyne cycloadducts.
Scheme 2
Scheme 2
Regioselectivity of 6,7-indolyne cycloadducts.
Scheme 3
Scheme 3
Regioselectivity of 5,6-difluoroindole-derived indolynes.
Scheme 4
Scheme 4
Cine substitution in 6,7-indolynes.
Scheme 5
Scheme 5
Exo- and regioselective ring-opening and aromatization in 6,7-indolyne furan cycloadducts.
Scheme 6
Scheme 6
Regio- and exo-selective ring-opening of 6,7-indolyne furan cycloadducts.
Scheme 7
Scheme 7
Fischer indole synthesis of 4,5- and 5,6-o-trimethylsilyl triflate indolyne precursors.
Scheme 8
Scheme 8
4,5-, 5,6-, and 6,7-indolynes derived from o-silyltriflates.
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References

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    1. For attempts to generate the elusive 2,3-indolyne, see: Conway SC, Gribble GW. Heterocycles. 1992;34:2095–2108.Gribble GW, Conway SC. Synth Commun. 1992;22:2129–2141.

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