Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Mar 23;133(11):3832-5.
doi: 10.1021/ja200437g. Epub 2011 Feb 25.

Overturning indolyne regioselectivities and synthesis of indolactam V

Sarah M Bronner  1 , Adam E Goetz, Neil K Garg
Affiliations

Overturning indolyne regioselectivities and synthesis of indolactam V

Sarah M Bronner et al. J Am Chem Soc. .

Abstract

We report the design and synthesis of an indolyne that displays a reversal in regioselectivity, in both nucleophilic addition and cycloaddition reactions, compared to typical 4,5-indolynes. Our approach utilizes simple computations to predict regioselectivity in reactions of unsymmetrical arynes. With this methodology, novel benzenoid-substituted indoles can be accessed with significant regiocontrol. Furthermore, the technology provides an unconventional tactic for the synthesis of C4-substituted indole alkaloids, as demonstrated by a synthesis of indolactam V.

PubMed Disclaimer

Figures

Figure 1
Figure 1
C4-substituted alkaloids 1–4 and indolynes 5 and 6.
Scheme 1
Scheme 1
Scheme 2
Scheme 2
See this image and copyright information in PMC

References

    1. For reviews, see: Pellissier H, Santelli M. Tetrahedron. 2003;59:701–730.Wenk HH, Winkler M, Sander W. Angew. Chem. Int. Ed. 2003;42:502–528.Sanz R. Org. Prep. Proced. Int. 2008;40:217–291.Chen Y, Larock RC. Arylation Reactions Involving the Formation of Arynes. In: Ackermann L, editor. Modern Arylation Methods. Wiley–VCH; Weinheim: 2009. pp. 401–473.

    1. With the exception of 3-alkoxybenzynes, most unsymmetrical arynes show modest or variable regioselectivity. For pertinent reviews, see ref . For recent examples involving naphthalynes, see: Jin T, Yamamoto Y. Angew. Chem. Int. Ed. 2007;46:3323–3325.Rémond E, Tessier A, Leroux FR, Bayardon J, Jugé S. Org. Lett. 2010;12:1568–1571. For recent examples involving 3-alkylbenzynes, see: Spiter C, Keeling S, Moses JE. Org. Lett. 2010;12:3368–3371.Crossley JA, Browne DL. Tetrahedron Lett. 2010;51:2271–2273.Hari Y, Sone R, Aoyama T. Org. Biomol. Chem. 2009;7:2804–2808.Akai S, Ikawa T, Takayanagi S.-i., Morikawa Y, Mohri S, Tsubakiyama M, Egi M, Wada Y, Kita Y. Angew. Chem. Int. Ed. 2008;47:7673–7676. For benzynocycloalkanes, see: Hamura T, Ibusuki Y, Sato K, Matsumoto T, Osamura Y, Suzuki K. Org. Lett. 2003;5:3551–3554. Scattered reports involving 3-silylbenzynes have appeared, which can react with significant regioselectivities; see: Dai M, Wang Z, Danishefsky SJ. Tetrahedron Lett. 2008;49:6613–6616.Matsumoto T, Sohma T, Hatazaki S, Suzuki K. Synlett. 1993:843–846.; see also ref . For a recent example of alkoxybenzynes undergoing regioselective reactions, see: Tadross PM, Gilmore CD, Bugga P, Virgil SC, Stoltz BM. Org. Lett. 2010;12:1224–1227. see also references therein.

    1. Cheong PH-Y, Paton RS, Bronner SM, Im G-Y, Garg NK, Houk KN. J. Am. Chem. Soc. 2010;132:1267–1269. - PMC - PubMed
    2. Im G-Y, Bronner SM, Goetz AE, Paton RS, Cheong PH-Y, Houk KN, Garg NK. J. Am. Chem. Soc. 2010;132:17933–17944. - PMC - PubMed

    1. For seminal indolyne studies, see: Julia M, Huang Y, Igolen J. C. R. Acad. Sci., Ser. C. 1967;265:110–112.Igolen J, Kolb A. C. R. Acad. Sci., Ser. C. 1969;269:54–56. For related studies, see: Julia M, Goffic FL, Igolen J, Baillarge M. C. R. Acad. Sci., Ser. C. 1967;264:118–120.Julia M, Igolen J, Kolb M. C. R. Acad. Sci., Ser. C. 1971;273:1776–1777.

    1. For recent indolyne studies, see: Bronner SM, Bahnck KB, Garg NK. Org. Lett. 2009;11:1007–1010.Tian X, Huters AD, Douglas CJ, Garg NK. Org. Lett. 2009;11:2349–2351.Buszek KR, Luo D, Kondrashov M, Brown N, VanderVelde D. Org. Lett. 2007;9:4135–4137.Brown N, Luo D, VanderVelde D, Yang S, Brassfield A, Buszek KR. Tetrahedron Lett. 2009;50:63–65.Buszek KR, Brown N, Luo D. Org. Lett. 2009;11:201–204.Brown N, Luo D, Decapo JA, Buszek KR. Tetrahedron Lett. 2009;50:7113–7115.Garr AN, Luo D, Brown N, Cramer CJ, Buszek KR, VanderVelde D. Org. Lett. 2010;12:96–99.

Publication types

MeSH terms