Organic Letters
Letter
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Addition/Domino Electrophilic Cyclization Cascade: Synthesis of
Cyclohepta[b]indoles. J. Org. Chem. 2018, 83, 8615−8626.
(b) Goswami, P.; Borah, A. J.; Phukan, P. Formation of Cyclohepta-
[
b]Indole Scaffolds via Heck Cyclization: A Strategy for Structural
Analogues of Ervatamine Group of Indole Alkaloid. J. Org. Chem.
015, 80, 438−446. (c) Liu, C.; Widenhoefer, R. A. Palladium-
AUTHOR INFORMATION
■
2
Catalyzed Cyclization/Carboalkoxylation of Alkenyl Indoles. J. Am.
Chem. Soc. 2004, 126, 10250−10251. (d) Ferreira, E. M.; Stoltz, B. M.
Catalytic C-H Bond Functionalization with Palladium(II): Aerobic
Oxidative Annulations of Indoles. J. Am. Chem. Soc. 2003, 125, 9578−
9579. (e) Ishikura, M.; Kato, H. A Synthetic Use of the
Intramolecular Alkyl Migration Process in Indolylborates for Intra-
molecular Cyclization: A Novel Construction of Carbazole Deriva-
tives. Tetrahedron 2002, 58, 9827−9838.
ORCID
Author Contributions
All authors have given approval to the final version of the
manuscript.
(11) (a) Mishra, U. K.; Yadav, S.; Ramasastry, S. S. V. One-Pot
Multicatalytic Approaches for the Synthesis of Cyclohepta[b]Indoles,
Indolotropones, and Tetrahydrocarbazoles. J. Org. Chem. 2017, 82,
Notes
The authors declare no competing financial interest.
6729−6737. (b) Bennasar, M.-L.; Zulaica, E.; Sole, D.; Alonso, S.
́
Sequential ring-closing metathesis−vinyl halide Heck cyclization
reactions: access to the tetracyclic ring system of ervitsine.
Tetrahedron 2012, 68, 4641−4648.
ACKNOWLEDGMENTS
■
S.F. and A.P. gratefully acknowledge financial support from the
National Science Foundation (CHE-1566086) and Georgia
Tech. A.P. also thanks the National Science Foundation for an
AGEP-GRS under the parent award. Single-crystal diffraction
experiments were performed at the Georgia Tech SCXRD
facility directed by Dr. John Bacsa.
(12) Chakraborty, A.; Goswami, K.; Adiyala, A.; Sinha, S. Syntheses
of Spiro[cyclopent[3]ene-1,3′-indole]s and Tetrahydrocyclohepta[b]-
indoles from 2,3-Disubstituted Indoles through Sigmatropic Rear-
rangement. Eur. J. Org. Chem. 2013, 2013, 7117−7127.
(13) For examples of [4 + 3] cycloadditions toward cyclohepta[b]
indoles: (a) Gelis, C.; Levitre, G.; Merad, J.; Retailleau, P.; Neuville,
L.; Masson, G. Highly Diastereo- and Enantioselective Synthesis of
Cyclohepta[b]indoles by Chiral-Phosphoric-Acid-Catalyzed (4 + 3)
Cycloaddition. Angew. Chem., Int. Ed. 2018, 57, 12121−12125.
REFERENCES
■
(
1) Stempel, E.; Gaich, T. Cyclohepta[b]indoles: A Privileged
Structure Motif in Natural Products and Drug Design. Acc. Chem. Res.
016, 49, 2390−2402 and references therein .
2) Carroll, A. R.; Hyde, E.; Smith, J.; Quinn, R. J.; Guymer, G.;
Forster, P. I. Actinophyllic Acid, a Potent Indole Alkaloid Inhibitor of
the Coupled Enzyme Assay Carboxypeptidase U/Hippuricase from
the Leaves of Alstonia actinophylla (Apocynaceae). J. Org. Chem.
005, 70, 1096−1099.
3) Liu, B.-Y.; Zhang, C.; Zeng, K.-W.; Li, J.; Guo, X.-Y.; Zhao, M.-
(b) Xu, G.; Chen, L.; Sun, J. Rhodium-Catalyzed Asymmetric
Dearomative [4 + 3]-Cycloaddition of Vinylindoles with Vinyl-
diazoacetates: Access to Cyclohepta[b]Indoles. Org. Lett. 2018, 20,
2
(
3
408−3412. (c) Li, Y.; Zhu, C.-Z.; Zhang, J. Gold-Catalyzed [4 + 3]
Cycloaddition/C-H Functionalization Cascade: Regio- and Diaster-
eoselective Route to Cyclohepta[b]Indoles. Eur. J. Org. Chem. 2017,
2017, 6609−6613. (d) Zhang, H.-H.; Zhu, Z.-Q.; Fan, T.; Liang, J.;
2
(
Shi, F. Intermediate-Dependent Unusual [4 + 3], [3 + 2] and Cascade
Reactions of 3-Indolylmethanols: Controllable Chemodivergent and
Stereoselective Synthesis of Diverse Indole Derivatives. Adv. Synth.
Catal. 2016, 358, 1259−1288. (e) Zhang, J.; Shao, J.; Xue, J.; Wang,
Y.; Li, Y. One pot hydroamination/[4 + 3] cycloaddition: synthesis
towards the cyclohepta[b]indole core of silicine and ervatamine. RSC
Adv. 2014, 4, 63850−63854. (f) He, S.; Hsung, R. P.; Presser, W. R.;
Ma, Z.-X.; Haugen, B. J. An Approach to Cyclohepta[b]indoles
through an Allenamide [4 + 3] Cycloaddition-Grignard Cyclization-
Chugaev Elimination Sequence. Org. Lett. 2014, 16, 2180−2183.
B.; Tu, P.-F.; Jiang, Y. Exotines A and B, Two Heterodimers of
Isopentenyl-Substituted Indole and Coumarin Derivatives from
Murraya exotica. Org. Lett. 2015, 17, 4380−4383.
(
4) Andriantsiferana, M.; Besselievre, R.; Riche, C.; Husson, H. P.
Structure of ervitsine, a new type of α-acylindolic alkaloid.
Tetrahedron Lett. 1977, 18, 2587−90.
5) Napper, A. D.; Hixon, J.; McDonagh, T.; Keavey, K.; Pons, J.-F.;
(
Barker, J.; Yau, W. T.; Amouzegh, P.; Flegg, A.; Hamelin, E.; Thomas,
R. J.; Kates, M.; Jones, S.; Navia, M. A.; Saunders, J. O.; DiStefano, P.
S.; Curtis, R. Discovery of indoles as potent and selective inhibitors of
the deacetylase SIRT1. J. Med. Chem. 2005, 48, 8045−8054.
(g) Shu, D.; Song, W.; Li, X.; Tang, W. Rhodium- and Platinum-
Catalyzed [4 + 3] Cycloaddition with Concomitant Indole
Annulation: Synthesis of Cyclohepta[b]Indoles. Angew. Chem., Int.
Ed. 2013, 52, 3237−3240. (h) Han, X.; Li, H.; Hughes, R. P.; Wu, J.
Gallium(III)-Catalyzed Three-Component (4 + 3) Cycloaddition
Reactions. Angew. Chem., Int. Ed. 2012, 51, 10390−10393.
(14) (a) Takeda, T.; Harada, S.; Okabe, A.; Nishida, A.
Cyclohepta[b]indole Synthesis through [5 + 2] Cycloaddition:
Bifunctional Indium(III)-Catalyzed Stereoselective Construction of
7-Membered Ring Fused Indoles. J. Org. Chem. 2018, 83, 11541−
11551. (b) Mei, G.; Yuan, H.; Gu, Y.; Chen, W.; Chung, L. W.; Li, C.
Dearomative Indole [5 + 2] Cycloaddition Reactions: Stereoselective
Synthesis of Highly Functionalized Cyclohepta[b]Indoles. Angew.
Chem., Int. Ed. 2014, 53, 11051−11055.
(15) Shenje, R.; Martin, M. C.; France, S. A Catalytic
Diastereoselective Formal [5 + 2] Cycloaddition Approach to
Azepino[1,2-a]indoles: Putative Donor-Acceptor Cyclobutanes as
Reactive Intermediates. Angew. Chem., Int. Ed. 2014, 53, 13907−
13911.
(16) For seminal contributions, see: (a) Begouin, J.-M.; Niggemann,
M. Calcium-Based Lewis Acid Catalysts. Chem. - Eur. J. 2013, 19,
8030−8041. (b) Niggemann, M.; Meel, M. Calcium-catalyzed
(
6) Barf, T.; Lehmann, F.; Hammer, K.; Haile, S.; Axen, E.; Medina,
C.; Uppenberg, J.; Svensson, S.; Rondahl, L.; Lundbaeck, T. N-
Benzylindolocarboxylic acids: Design and synthesis of potent and
selective adipocyte fatty-acid binding protein (A-FABP) inhibitors.
Bioorg. Med. Chem. Lett. 2009, 19, 1745−1748.
(
7) Kuehm-Caubere, C.; Caubere, P.; Jamart-Gregoire, B.; Pfeiffer,
B.; Guardiola-Lemaitre, B.; Manechez, D.; Renard, P. Novel
thiopyrano[3,2-b] and cycloalkeno[1,2-b]indole derivatives with
high inhibitory properties in LTB4 production. Eur. J. Med. Chem.
1
(
999, 34, 51−61.
8) For representative examples, see: (a) Tang, W.; Li, X.
Preparation of cyclopropyl indoles and cyclohepta[b]indoles and
therapeutic uses thereof. WO2016090094A1, 2016. (b) Kinnick, M.
D.; Mihelich, E. D.; Morin, J. M., Jr.; Sall, D. J.; Sawyer, J. S.
Preparation of cyclohepta[b]indole derivatives as sPLA2 inhibitors.
WO2003016277A1, 2003.
9) Robinson, B. Studies on the Fischer Indole Synthesis. Chem. Rev.
969, 69, 227−250.
10) For pertinent examples, see: (a) Jadhav, A. S.; Pankhade, Y. A.;
Vijaya Anand, R. Exploring Gold Catalysis in a 1,6-Conjugate
(
1
(
E
Org. Lett. XXXX, XXX, XXX−XXX