Platinum(II)-catalyzed generation and [3+2] cycloaddition reaction of α,β-unsaturated carbene complex intermediates for the preparation of polycyclic compounds

Article abstract of DOI:10.1021/ja108586d

Pt(II)-catalyzed generation of unsaturated carbene complex intermediates from various propargyl ether derivatives based on electrophilic activation of alkynes was realized. These in situ generated unsaturated carbene complexes undergo [3+2] cycloaddition reaction with various vinyl ethers, leading to efficient formation of indoles, naphthols, and benzofuran fused with a five-membered ring in high yields.

Full text of DOI:10.1021/ja108586d

COMMUNICATION
pubs.acs.org/JACS
Platinum(II)-Catalyzed Generation and [3þ2] Cycloaddition Reaction
of R,β-Unsaturated Carbene Complex Intermediates for the
Preparation of Polycyclic Compounds
Kodai Saito, Hideyuki Sogou, Takuya Suga, Hiroyuki Kusama, and Nobuharu Iwasawa*
Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo 152-8551, Japan
S Supporting Information
b
Scheme 1. Catalytic Generation of R,β-Unsaturated Carbene
Complex Intermediates
ABSTRACT: Pt(II)-catalyzed generation of unsaturated
carbene complex intermediates from various propargyl
ether derivatives based on electrophilic activation of alkynes
was realized. These in situ generated unsaturated carbene
complexes undergo [3þ2] cycloaddition reaction with
various vinyl ethers, leading to efficient formation of indoles,
naphthols, and benzofuran fused with a five-membered ring
in high yields.
that the alkoxy group at the propargylic position would work not
only as an appropriate leaving group to generate unsaturated
carbene complex C but also as a base to deprotonate from the
ammonium part in the cyclized zwitterionic intermediate B. We
further expected that the generated unsaturated carbene complex
C would react with an electron-rich olefin in a [3þ2] cycloaddi-
tion manner to give a tricyclic indole derivative with regeneration
of the catalyst (Scheme 2).
Based on these considerations, the reaction of 2-(3-methox-
yprop-1-ynyl)aniline derivative 1a with 10 equiv of n-butyl vinyl
ether as a trapping reagent of the R,β-unsaturated carbene
complex intermediate was examined, employing typical electro-
philic transition metal catalysts. While most of the catalysts
examined, such as gold(I), rhenium(I), and tungsten(0) com-
plexes, afforded a complex mixture of products or recovery of the
starting material, the desired [3þ2] cycloadduct 2a was obtained
when 1a was treated with platinum(II) catalysts.1 Although PtCl2
itself was not so efficient due to its lower solubility, [PtCl2-
(C2H4)]2 gave better results, and addition of an equimolar
amount (based on Pt) of PPh3 somewhat improved the yield,
probably because the higher electron density on the platinum(II)
would promote elimination of methoxide from the zwitterionic
intermediate.10
Thus, by carrying out the reaction of 1a and butyl vinyl ether
with 2.5 mol % of the [PtCl2(C2H4)]2 (5 mol % based on Pt) and
5 mol % of PPh3 at 100 °C in 1,4-dioxane in the presence of
Na2CO3 as base,11 tricyclic indole 2a could be obtained in 83%
yield.
The proposed mechanism for the formation of 2a is shown in
Scheme 2. 5-Endo nucleophilic attack of the amine nitrogen onto
the alkyne, activated electrophilically by Pt(II), occurred to give a
zwitterionic intermediate B. Elimination of the methoxy group
by electron-donation from the alkenyl metallic part, along with
ransition metal-catalyzed generation of carbene complex
T
and related species based on the electrophilic activation of
alkynes has attracted much attention as a useful method for the
construction of cyclic carbon skeletons.1 In contrast, catalytic
generation of R,β-unsaturated carbene complex species based on
this strategy has been limited to the study utilizing 1,2-acyloxy
migration of propargyl ester derivatives,2 and only a few addi-
tional examples have been reported, such as the reactions of
homopropargyl azide,3a propargyl ketals,3b propargyl thioketal,3c
etc.3d,3e Furthermore, the reaction of generated R,β-unsaturated
carbene complexes was mostly limited to cyclopropanation,4
1,2-hydrogen shift,3a ylide formation,3b etc.5
We have become interested in developing a general method
for catalytic generation of R,β-unsaturated carbene complex
intermediates and in utilizing the intermediates for further
unique carbon-carbon bond formation to realize a facile method
for the preparation of synthetically useful polycyclic compounds.
Our basic strategy is as follows: By treatment of propargyl alcohol
derivatives containing a nucleophilic part in an appropriate
position with an electrophilic transition metal catalyst, cyclic
R,β-unsaturated carbene complexes A would be generated by
intramolecular addition of the nucleophilic moiety to the elec-
trophilically activated alkyne in an endo manner, followed by
elimination of the leaving group at the propargylic position.
Furthermore, we expected that [3þ2] cycloaddition reaction of
the generated R,β-unsaturated carbene complexes A with elec-
tron-rich alkenes6-9 would be a new type of transformation to
realize efficient synthesis of various useful polycyclic compounds
(Scheme 1). In this paper we describe successful realization of
this type of reaction using Pt(II) catalysts.
We have chosen a propargyl ether 1a connected with a Boc-
protected amine as a nucleophile through the aromatic ring, with
the expectation that the rigid planar structure would facilitate
endo-cyclization to the electrophilically activated alkyne part and
Received: October 1, 2010
Published: December 21, 2010
r
2010 American Chemical Society
689
dx.doi.org/10.1021/ja108586d J. Am. Chem. Soc. 2011, 133, 689–691
|

Journal of the American Chemical Society
COMMUNICATION
Scheme 2. Reaction of Aniline Derivative 1a with n-Butyl
Vinyl Ether
be employed as substrate to give the corresponding tricyclic
indoles 2i, 2j, and 2k in good yield (Table 1, entries 8-10).13
Furthermore, substrates containing other kinds of nucleophi-
lic parts could also be employed in this reaction. When the
substrates 3 having a silyl enol ether as carbon nucleophile were
applied to this reaction, a variety of naphthol derivatives 4, fused
with a five-membered ring, were obtained in good yield
(eq 1).13,14 Even phenol derivative 5 gave the corresponding
benzofuran derivative 6 in 83% yield (eq 2). Therefore, this
reaction could be applied to propargyl ethers containing a
nucleophilic moiety in general for the efficient synthesis of
various polycyclic compounds.
Table 1. Generality of the Reaction
entry
R1
R2
R3
R
R0
yield (%)a
1
t-Bu
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1b)
MeO (1c)
F(1d)
79 (2b)
88 (2c)
70 (2d)
82 (2e)
63 (2f)
70 (2g)c
73 (2h)
68 (2i)d
67 (2j)
80 (2k)
2
c-Hex
H
H
H
H
H
H
Me
H
H
3
-(CH2)2Cl
PMB
In conclusion, we have developed a Pt(II)-catalyzed genera-
tion of unsaturated carbene complex intermediates from various
propargyl ether derivatives based on electrophilic activation of
alkynes. These in situ generated unsaturated carbene complexes
undergo [3þ2] cycloaddition reaction with various vinyl ethers
as a two-carbon unit, leading to efficient formation of indoles,
naphthols, and benzofuran fused with a five-membered ring in
high yields.
4
5
6b
-(CH2)2-
Et
Me
Me
H
7
Et
8
n-Bu
n-Bu
n-Bu
9
H
10
H
a Isolated yield. b PtCl2 (5 mol %) was used as catalyst. c Diastereomer
ratio 66:34 determined by H NMR. d Diastereomer ratio 4:1 deter-
1
’ ASSOCIATED CONTENT
mined by 1H NMR.
S
Supporting Information. Preparative methods and spec-
b
deprotonation from the ammonium nitrogen, then occurred
to give unsaturated carbene complex C. Nucleophilic attack of
n-butyl vinyl ether to the β-carbon of the R,β-unsaturated
carbene moiety generated alkenyl metallic intermediate D, which
underwent intramolecular nucleophilic attack onto the oxonium
carbon to afford the final product 2a with regeneration of the
catalyst. It should be noted that there is no general method for
the [3þ2] cycloaddition reaction with electron-rich alkenes6-8
of unsaturated carbene complexes generated catalytically, based
on the electrophilic activation of alkynes.
tral and analytical data for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
niwasawa@chem.titech.ac.jp
’ ACKNOWLEDGMENT
The generality of this tricyclic indole synthesis12 is quite high,
and various alkyl vinyl ethers, such as tert-butyl and p-methox-
ybenzyl vinyl ethers (Table 1, entries 1-4) and di- and trisub-
stituted vinyl ethers (Table 1, entries 5-7), reacted smoothly to
afford the corresponding substituted tricyclic indoles in good
yield.13 Furthermore, aniline derivatives having a methyl sub-
stituent at the propargylic position 1b and an electron-donating
or -withdrawing group on the aromatic ring 1c or 1d could also
This research was partly supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology of Japan.
’ REFERENCES
(1) For recent reviews, see: (a) F€urstner, A.; Davies, P. W. Angew.
Chem., Int. Ed. 2007, 46, 3410–3449. (b) Jimꢀenez-Nꢀu~nez, E.; Echavarren,
A. M. Chem. Rev. 2008, 108, 3326–3350. (c) Zhang, L.; Sun, J.;
690
dx.doi.org/10.1021/ja108586d |J. Am. Chem. Soc. 2011, 133, 689–691

Journal of the American Chemical Society
COMMUNICATION
Kozmin, S. A. Adv. Synth. Catal. 2006, 348, 2271–2296. (d) F€urstner,
A. Chem. Soc. Rev. 2009, 38, 3208–3221. (e) Shen, H. C. Tetrahedron
2008, 64, 7847–7870.
(2) For recent reviews of transition metal-catalyzed 1,2-acyloxy
migration, see: (a) Marco-Contelles, J.; Soriano, E. Chem. Eur.
J. 2007, 13, 1350–1357. (b) Marion, N.; Nolan, S. P. Angew. Chem.,
Int. Ed. 2007, 46, 2750–2752. (c) Marion, N.; Lemiꢁere, G.; Correa, A.;
Costabile, C.; Ramꢀon, R. S.; Moreau, X.; Frꢀemont, P.; Dahmane, R.;
Hours, A.; Lesage, D.; Tabet, J.-C.; Goddard, J.-P.; Gandon, V.; Cavallo,
L.; Fensterbank, L.; Malacria, M.; Nolan, S. P. Chem. Eur. J. 2009, 15,
3243–3260.
(3) (a) Gorin, D. J.; Davis, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005,
127, 11260–11261. (b) Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2008,
130, 12598–12599. (c) Peng, L.; Zhang, X.; Zhang, S.; Wang, J. J. Org.
Chem. 2007, 72, 1192–1197. (d) Sanz, R.; Miguel, D.; Gohain, M.;
García-García, P.; Fernꢀandez-Rodríguez, M. A.; Gonzꢀalez-Pꢀerez, A.;
ꢀ
Nieto-Faza, O.; de Lera, A. R.; Rodríguez, F. Chem. Eur. J. 2010, 16,
9818–9828. See also (e) Lin, G.-Y.; Li, C.-W.; Hung, S.-H.; Liu, R.-S.
Org. Lett. 2008, 10, 5059–5062.
(4) For examples of cyclopropanation reaction by using unsaturated
carbene complexes generated from 1,2-acyloxy migration of propargyl
esters, see: (a) Rautenstrauch, V. J. Org. Chem. 1984, 49, 950–952.
(b) Miki, K.; Ohe, K.; Uemura, S. J. Org. Chem. 2003, 68, 8505–8513.
(c) Mainetti, E.; Mouriꢁes, V.; Fensterbank, L.; Malacria, M.; Marco-
Contelles, J. Angew. Chem., Int. Ed. 2002, 41, 2132–2135. (d) Johansson,
M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J.Am. Chem. Soc. 2005, 127,
18002–18003.
(5) For other cycloaddition reactions, see: (a) Shapiro, N. D.; Toste,
F. D. J. Am. Chem. Soc. 2008, 130, 9244–9245. (b) Shapiro, N. D.; Shi, Y.;
Toste, F. D. J. Am. Chem. Soc. 2009, 131, 11654–11655. (c) Zheng, H.;
Zheng, J.; Yu, B.; Chen, Q.; Wang, X.; He, Y.; Yang, Z.; She, X. J. Am.
Chem. Soc. 2010, 132, 1788–1789.
(6) One specific example of the [3þ2] cycloaddition reaction with
an electron-rich olefin, N-benzylindole, of R,β-unsaturated carbene
complexes generated catalytically from a propargyl ketal using Au(I)
catalyst was reported. See ref 3b.
(7) Recently, [3þ2] cycloaddition reaction with electron-deficient
alkynes of R,β-unsaturated carbene complexes generated catalytically
from propargyl esters using Rh(I) catalyst based on electrophilic
activation of the alkyne moiety was reported: Shibata, Y.; Noguchi, K.;
Tanaka, K. J. Am. Chem. Soc. 2010, 132, 7896–7898.
(8) For [3þ2] cycloaddition reaction with electron-rich olefins of
R,β-unsaturated carbenoids generated catalytically from corresponding
diazo compounds with Rh(I) catalyst, see: Lian, Y.; Davies, H. M. L.
J. Am. Chem. Soc. 2010, 132, 440–441 and references cited therein. See
also: Lu, S.; Jin, T.; Bao, M.; Yamamoto, Y. Org. Lett. 2010, 12, 864–866.
(9) For examples of stoichiometiric [3þ2] cycloaddition reactions
of alkenyl Fischer carbene complexes with two-carbon unit, see the
following reviews: (a) D€otz, K. H.; Stendel, J., Jr. Chem. Rev. 2009, 109,
3227–3274. (b) de Meijere, A.; Schirmer, H.; Duetsch, M. Angew. Chem.,
Int. Ed. 2000, 39, 3964–4002.
(10) For examples of similar platinum(II) monophosphine complex-
catalyzed cyclization reactions, see: (a) Bender, C. F.; Widenhoefer,
R. A. J. Am. Chem. Soc. 2005, 127, 1070–1071. (b) Kusama, H.; Ebisawa,
M.; Funami, H.; Iwasawa, N. J. Am. Chem. Soc. 2009, 131, 16352–16353.
(11) Addition of Na2CO3 improved the yield of the product.
(12) For a review on tandem reactions for indole synthesis, see:
Barluenga, J.; Rodríguez, F.; Fa~nanꢀas, F. J. Chem. Asian J. 2009, 4, 1036–
1048.
(13) The relative configuration of 2g, 2i, and 4d could not be
determined by NOE measurement.
(14) When this reaction was performed by using PPh3 instead of
tris(o-MeOC6H4)3P, 4a was obtained in 73% yield.
691
dx.doi.org/10.1021/ja108586d |J. Am. Chem. Soc. 2011, 133, 689–691