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

• Published in: Tetrahedron letters Vol. 50; no. 1; pp. 63 - 65
• Main Authors: Brown, Neil, Luo, Diheng, Vander Velde, David, Yang, Shaorong, Brassfield, Allen, Buszek, Keith R.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 07.01.2009; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; TRIFLATE; 2-SUBSTITUTED FURANS; (+/-)-CIS-TRIKENTRIN-B; PHENOLS; TELEOCIDIN; DERIVATIVES; BENZYNE
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2008.10.086

The regioselectivity of Diels–Alder cycloadditions of indole arynes (indolynes) at all three benzenoid positions was examined. The 6,7-indolyne displayed virtually complete preference for the more sterically congested cycloaddduct, and undergoes an acid-catalyzed rearrangement to afford annulated enones. 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 anomalous 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.