Table 1. Initial Studies: Gold(I)-Catalyzed Intermolecular Re-
action between Cyclopropene 1a and Indole 9a
Scheme 1. Gold(I)-Catalyzed Indole Additions to Unactivated
Alkynes and Allenes
temp
time
(h)
3a:
4ab
yield
(%)
entry
catalyst
(°C)
1
PPh3AuNTf
rt
3
3
20:80
88:12
80:20
>95:5
1:99>
53%c 4a
59%d 3a
52%d 3a
91%d 3a
76%d 4a
2
10
10
10
10
rt
3e
4
0
3
0
3
5f
reflux
42
One of the research efforts within our group is to explore
the diverse chemistry of gold-catalyzed reactions with cyclo-
propenes.13ꢀ15 In this communication, we present a gold(I)-
catalyzed controlled approach toward either 3-(E)-vinylin-
doles 3or bis-indolylalkane 4from indole additions to 3,3-disub-
stituted cyclopropenes 1. Furthermore, we disclose a highly
unusual outcome when both substituents R1,R2 on 1 are bulky
(e.g., Cy): in this case, oxidation products bis-indolylalkene 5
and epoxide 6 are observed with only air as the oxidant.
Our investigations commenced with screening conditions
using indole and cyclopropene 1a (entries 1ꢀ3, Table 1).
Intriguingly, varying levels of 3a and 4a were observed,
depending on the catalyst and reaction conditions employed.
For example, at rt, PPh3AuNTf216 favored formation of 4a
whereas catalyst 1017 favors 3a.
a See Supporting Information for full optimization studies. b Deter-
mined by 1H NMR analysis of the crude mixture. c Isolated yield. d NMR
yield by comparison with an internal standard. e 1 equiv of indole 2
employed. f 2.2 equiv of indole 2 employed.
cyclopropene to form a carbene/cationic intermediate
I,13a,15f,15g which is trapped by indole to give intermediate
II. II then deaurates/protonates to yield vinylindole 3.
Under optimized conditions, vinylindole 3 can be further
activated by Au(I) or Hþ (III) to allow the attack of a
second equivalent of indole with intermediate IV to pro-
duce bis-indolylalkane 4.18 To ascertain if 3f4 is Au(I) or
Hþ catalyzed,6b isolated 3h was resubjected to 2-methy-
lindole and catalyst 10 in the presence and absence of 2,6-
di-tert-butylpyridine (to quench any Hþ that might be
present). Bis-indolylalkane 4h is only successfully pro-
duced in the absence of 2,6-di-tert-butylpyridine, implying
that 3f4 is either Hþ catalyzed or assisted. Deuterium
The proposed mechanism for the formation of 3 and 4 is
shown in Scheme 2. Gold(I) catalyzes the ring opening of
(10) (a) Ferrer, C.; Amijs, C. H. M.; Echavarren, A. M. Chem.;Eur. J.
ꢀ
~
ꢀ
2007, 13, 1358. (b) Barluenga, J.; Fernandez, A.; Rodrıguez, F.; Fananas,
F. J. J. Organomet. Chem. 2009, 694, 546. With propargyl carboxylates,
indoles trap the rearranged gold(I)-carbene intermediates to form vinylin-
ꢀ
doles:(c)Amijis, C. H. M.;Lopez-Carrillo, V.;Echavarren, A. M.Org. Lett.
2007, 9, 4021. For intramolecular, see: (d) Ferrer, C.; Echavarren, A. M.
Angew. Chem., Int. Ed. 2006, 45, 1105.
(11) Tarselli, M. A.; Liu, A.; Gagne, M. R. Tetrahedron 2009, 65, 1785.
(12) (a) Toups, K. L.; Liu, G. T.; Widenhoefer, R. A. J. Organomet.
Chem. 2009, 694, 571. For enantioselective version: (b) Wang, M.-Z.;
Zhou, C.-Y.; Guo, Z.; Wong, L.-M.; Wong, M.-K.; Che, C.-M. Chem.;
Asian. J. 2011, 6, 812. For additions to allenamides: (c) Kimber, M. C.
Org. Lett. 2010, 12, 1128.
Scheme 2. Proposed Mechanism for the Gold(I)-Catalyzed In-
dole Additions to Cyclopropenes
(13) (a) Bauer, J. T.; Hadfield, M. S.; Lee, A.-L. Chem. Commun. 2008,
6405. (b) Hadfield, M. S.; Lee, A.-L. Org. Lett. 2010, 12, 484. (c) Hadfield,
M. S.; Bauer, J. T.; Glen, P. E.; Lee, A.-L. Org. Biomol. Chem. 2010, 8, 4090.
(d) Hadfield, M. S.; Lee, A.-L. Chem. Commun. 2011, 47, 1333.
(14) Recent reviews on cyclopropene chemistry: (a) Zhu, Z.-B.; Wei,
Y.; Shi, M. Chem. Soc. Rev. 2011, 40, 5534. (b) Marek, I.; Simaan, S.;
Masarwa, A. Angew. Chem., Int. Ed. 2007, 46, 7364. (c) Rubin, M.;
Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117.
(15) For other gold(I)-catalyzed reactions with cyclopropenes, see:
(a) Zhu, Z.-B.; Shi, M. Chem.;Eur. J. 2008, 14, 10219. (b) Li, C.; Zeng,
Y.; Wang, J. Tetrahedron Lett. 2009, 50, 2956. (c) Li, C.; Zeng, Y.; Feng,
J.; Zhang, Y.; Wang, J. Angew. Chem., Int. Ed. 2010, 49, 6413. (d) Miege,
F.; Meyer, C.; Cossy, J. Org. Lett. 2010, 12, 4144. (e) Seraya, E.; Slack,
E.; Ariafard, A.; Yates, B. F.; Hyland, C. J. T. Org. Lett. 2010, 12, 4768.
€
(f) Seidel, G.; Mynott, R.; Furstner, A. Angew. Chem., Int. Ed. 2009, 48,
2510. (g) Benitez, D.; Shapiro, N. D.;Tkatchouk, E.;Wang, Y.;Goddard,
W. A., III; Toste, F. D. Nature Chem. 2009, 1, 482. Review: (h) Miege, F.;
Meyer, C.; Cossy, J. Beilstein J. Org. Chem. 2011, 7, 717.
ꢀ
(16) Mezailles, N.; Richard, L.; Gagosz, F. Org. Lett. 2005, 7, 4133.
Org. Lett., Vol. 14, No. 3, 2012
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