10.1002/adsc.201700932
Advanced Synthesis & Catalysis
General procedure for gold(I) catalyzed spirocyclization:
N-propargyl-tryptamine 1 (0.1 mmol) was placed into a
Schlenck tube filled with argon. Toluene (1.0 mL) and
acetic acid (6.0 μL, 0.1 mmol) were added and the stirred
solution was warmed to 70 °C before adding catalyst 4a
(3.9 mg, 0.005 mmol). The reaction mixture was stirred for
20 h and then allowed to cool to RT before being
concentrated under vacuum. Subsequent purification of the
crude mixture over silica gel chromatography provided the
product.
[3]
[4]
a) C. J. Douglas, L. E. Overman, Proc. Natl.
Acad. Sci. 2004, 101, 5363; b) B. M. Trost, C.
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Rivas, Tetrahedron 2016, 72, 6729.
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Chem. Res. 2014, 47, 925; g) R. Dorel, A. M.
Echavarren, Chem. Rev. 2015, 115, 9028.
3'-methylene-1'-(prop-2-yn-1-yl)spiro[indole-3,4'-
piperidine] (2a).
[5]
a) R. A. Widenhoefer, X. Han, Eur. J. Org. Chem.
2006, 2006, 4555; b) E. Jimenez-Nunez, A. M.
Echavarren, Chem. Commun. 2007, 333; c) H.
Huang, Y. Zhou, H. Liu, Beilstein J. Org. Chem.
2011, 7, 897; d) M. Bandini, Chem. Soc. Rev.
2011, 40, 1358; e) H. Ohno, Isr. J. Chem. 2013,
53, 869; f) P. M. Barbour, L. J. Marholz, L.
Chang, W. Xu, X. Wang, Chem. Lett. 2014, 43,
572.
Compound 2a was synthetized following the general
procedure using N-(2-(1H-indol-3-yl)ethyl)-N-(prop-2-yn-
1-yl)prop-2-yn-1-amine 1a (990 mg, 4.2 mmol). The
desired spiroindolenine 2a was obtained after column
chromatography on silica gel (gradient from 20 to 70 %
EtOAc:heptane) as a clear yellow oil (615 mg, 2.61 mmol,
62 %). Rf: 0.37 (EtOAc). IR (neat) υmax: 3291, 2919, 2808,
1646, 1547, 1464, 1432, 1329, 1196, 1133, 1073, 908, 750,
1
731, 645 cm-1. H NMR (CDCl3, 300 MHz) δ 8.36 (brs,
[6]
See, for example: a) C. Ferrer, A. M. Echavarren,
Angew. Chem. Int. Ed. 2006, 45, 1105; b) C.
Ferrer, C. H. M. Amijs, A. M. Echavarren, Chem.
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Cuesta, A. M. Echavarren, Tetrahedron 2009, 65,
9015; d) Y. Lu, X. Du, X. Jia, Y. Liu, Adv. Synth.
Catal. 2009, 351, 1517; e) V. A. Peshkov, O. P.
Pereshivko, E. V. Van der Eycken, Adv. Synth.
Catal. 2012, 354, 2841; f) A. S. K. Hashmi, W.
Yang, F. Rominger, Adv. Synth. Catal. 2012, 354,
1273; g) G. Cera, M. Chiarucci, A. Mazzanti, M.
Mancinelli, M. Bandini, Org. Lett. 2012, 14,
1350; h) S. G. Modha, A. Kumar, D. D.
Vachhani, J. Jacobs, S. K. Sharma, V. S. Parmar,
L. Van Meervelt, E. V. Van der Eycken, Angew.
Chem. Int. Ed. 2012, 51, 9572; i) J. D. Podoll, Y.
Liu, L. Chang, S. Walls, W. Wang, X. Wang,
Proc. Natl. Acad. Sci. 2013, 110, 15573; j) L.
Zhang, Y. Wang, Z.-J. Yao, S. Wang, Z.-X. Yu, J.
Am. Chem. Soc. 2015, 137, 13290; k) W. Xu, W.
Wang, X. Wang, Angew. Chem. Int. Ed. 2015, 54,
9546.
1H), 7.68 (d, J = 7.7 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H),
7.39 (td, J = 7.7 and 1.5 Hz, 1H), 7.30 (dd, J = 7.7 and 1.5
Hz, 1H), 4.82 (s, 1H), 4.60 (s, 1H), 3.54 (d, J = 13.0 Hz,
1H), 3.54 (s, 2H), 3.39 (d, J = 13.0 Hz, 1H), 3.08 (td, J =
11.8 and 4.5 Hz, 1H), 2.87 (ddd, J = 12.0, 10.4 and 3.2 Hz,
1H), 2.37 (t, J = 2.5 Hz, 1H), 2.12 (ddd, J = 13.4, 10.4 and
4.1 Hz, 1H), 1.77 (ddd, J = 13.4, 5.2 and 3.3 Hz, 1H). 13C
NMR (CDCl3, 75 MHz) δ 174.4 (CH), 155.1 (Cq), 141.2
(Cq), 140.5 (Cq), 128.5 (CH), 126.4 (CH), 123.7 (CH),
122.0 (CH), 111.4 (CH2), 78.1 (Cq), 74.2 (CH), 62.4 (Cq),
58.1 (CH2), 50.5 (CH2), 47.0 (CH2), 33.5 (CH2). HRMS
(ESI): calcd for C16H17N2 [M + H]+ 237.1386, found
237.1394.
Acknowledgements
VM thanks the ICSN for financial support. Nicolas Glinsky-
Olivier and Dr Valérian Gobé (ICSN) are thanked for
experimental assistance. We thank the ICSN and the IUF for
financial support. We used the computing facility of the CRIANN
(project 2006-013).
[7]
In
a
more general context, intramolecular
cyclizations of indoles on electrophiles delivering
2-substituted products are often argued to evolve
via spiroindolenines by C-3 to C-2 migrations.
See refs 6a-f and also for examples: a) C.-X.
Zhuo, Q.-F. Wu, Q. Zhao, Q.-L. Xu, S.-L. You, J.
Am. Chem. Soc. 2013, 135, 8169; b) C. C. J. Loh,
G. Raabe, D. Enders, Chem. Eur. J. 2012, 18,
13250.
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There is however no mention of the catalytic
activity of Au(I) complexes on this substrate.
V. Magné, F. Blanchard, A. Marinetti, A.
Voituriez, X. Guinchard, Adv. Synth. Catal. 2016,
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6
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