Rhodium-catalyzed cycloaddition of 1,6-enynes with 2-bromophenylboronic acids: Synthesis of a multi-substituted dihydronaphthalene scaffold

Article abstract of DOI:10.1039/b910532h

A formal [2 + 2 + 2] cycloaddition of a 1,6-enyne with 2-bromophenylboronic acid has been realized to construct a multi-substituted dihydronaphthalene scaffold, in which the direct reductive elimination mechanism of aryl-Rh(iii)-C sp³ species h

Full text of DOI:10.1039/b910532h

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COMMUNICATION
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Rhodium-catalyzed cycloaddition of 1,6-enynes with
2-bromophenylboronic acids: synthesis of a multi-substituted
dihydronaphthalene scaffoldw
Xianjie Fang, Chaolong Li and Xiaofeng Tong*
Received (in Cambridge, UK) 28th May 2009, Accepted 29th June 2009
First published as an Advance Article on the web 28th July 2009
DOI: 10.1039/b910532h
A formal [2 + 2 + 2] cycloaddition of a 1,6-enyne with
2-bromophenylboronic acid has been realized to construct a
multi-substituted dihydronaphthalene scaffold, in which the
direct reductive elimination mechanism of aryl-Rh(III)-Csp3
species has been established to form an aryl-Csp3 bond.
on. With respect to arylbromides as FGs, intermediate B
would undergo the oxidative addition of the C–Br bond to
the vinyl–Rh(I) bond to form C, which has been proposed as a
key intermediate by Chatani et al.7 Inspired by their work, we
envisioned that the insertion of olefins would occur prior to
the oxidative addition step if one CQC double bond was
introduced into B in an intramolecular way. As a result,
intermediate D would be formed. Apparently, 1,6-enyne
substrates8 would be a suitable platform to fulfil this strategy.
In this Communication, we report a new Rh(I)-catalyzed
reaction of 1,6-enynes with 2-bromophenylboronic acid that
provides a facile pathway to multi-substituted 1,2-dihydro-
naphthalene derivatives.9
As powerful and efficient methods for multiple C–C bond
formation, transition metal-catalyzed tandem reactions have
been widely developed.1 The advantages of these reactions are
the formation of several bonds in a one-pot procedure using a
single catalyst without either isolation of intermediates or a
change in reaction conditions, high efficiency and favorable
environmental considerations. Recently, the Rh(I)-catalyzed
tandem reactions of alkynes with ortho-functionalized
arylboronic acids, which lead to structurally complex
molecules from relatively ready-available substrates, have
been extensively studied.2 As shown in Scheme 1, the reaction
is initiated by the insertion of the alkyne into the aryl–
rhodium(I) bond of species A, which is generated via the
transmetalation of a Rh(I) complex with ortho-functionalized
arylboronic acids, to give vinylrhodium(I) intermediate B. The
flexibility of B has been demonstrated through its reaction
with different functional groups (FG), such as aldehydes and
ketones,3 electron-deficient olefins,4 –CH2Cl,5 nitriles,6 and so
To test our hypothesis, initial experiments were performed
on the reaction between 2-bromophenylboronic acid (1) and
1,6-enyne 2a in the presence of 10 mol% of Rh(I) (Table 1).
Fortunately, product 3a was isolated under the reaction
conditions of Rh(CO)2(acac) (10 mol%) and K2CO3
(1.2 equiv.), although the yield was as low as 21% (Table 1,
entry 1). The ligands PPh3 and BINAP obviously had a
positive effect on the yield, and the best results were obtained
when the ratio of PPh3 to Rh(I) was 2 : 1 (Table 1, entries 2–4).
The nature of the base also had an important impact on the
Table 1 Optimization of the Rh(I)-catalyzed reaction of 2a with 1a
Entry
Rh(I)
Ligand
—
PPh3
Base
Yield (%)c
1
2
3
4
5
6
7
8
Rh(CO)2(acac)
Rh(CO)2(acac)
Rh(CO)2(acac)
Rh(CO)2(acac)
Rh(CO)2(acac)
Rh(CO)2(acac)
RhCl(COD)
RhCl(COD)
RhCl(PPh)3
RhOH(COD)
RhOH(COD)
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
KOH
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
21
64
73
40
50
Trace
17
o10
Trace
25
b
PPh3
BINAPb
PPh3
PPh3
—
Scheme 1 Strategies for the Rh(I)-catalyzed reactions of alkynes with
2-bromophenylboronic acids.
BINAPb
—
—
9
10
11
Key Laboratory for Advanced Materials and Institute of Fine
Chemicals, East China University of Science and Technology,
Shanghai 200237, China. E-mail: tongxf@ecust.edu.cn;
Tel: +86 21-64253881
w Electronic supplementary information (ESI) available: Experimental
details, and spectroscopic and analytical data for all new compounds.
See DOI: 10.1039/b910532h
PPh3
56
a
Reaction conditions: 2a (0.3 mmol),
(0.03 mmol), ligand (0.06 mmol), base (0.36 mmol) in dioxane/H2O
1 (0.45 mmol), Rh(I)
b
(20 : 1, 3 mL) at 100 1C for 5 h. 10 mol% of ligand was added.
Isolated yield.
c
ꢀc
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Table 2 The Rh(I)-catalyzed cycloaddition of 1 and 2a
found to be slightly less effective than Rh(CO)2(acac) (Table 1,
entries 10 and 11).
With the optimized conditions in hand, we further examined
the scope of this new [2 + 2 + 2] cycloaddition by using a
variety of 1,6-enynes (Table 2). In general, 1,6-enynes with an
electron-deficient alkyne presented better results than
those with an electron-rich alkyne. Both nitrogen- and
oxygen-linked 1,6-enynes could be employed with similar
performance. Primary alkyl groups, as well as the phenyl
group, can be used as substituents on the alkyne, but the
latter had a negative effect on the reaction, probably due to its
steric bulk (Table 2, entry 8). The complex RhOH(COD)
catalyst was found to be more efficient for 1,6-enynes with a
phenyl substituent on the alkyne (Table 2, entry 9). It is worth
noting that a quaternary carbon atom in product 3i can be
easily established from substrate 2i under the same conditions
(eqn (1)).
Entry 1,6-Enyne
Product
Time/h Yield (%)c
1
2
2a
2b
5
4
3a
3b
73
64
ð1Þ
3
4
2c
2d
4
8
3c
3d
69
62
The proposed mechanism for this [2 + 2 + 2] cyclo-
addition is believed to follow the path shown in Scheme 2.
Transmetalation firstly occurs between the Rh(I) complex and
1 to give an arylrhodium complex.10 Next, insertion of the
alkyne of the 1,6-enyne substrate into the aryl–rhodium bond
produces vinylrhodium(I) intermediate E, which is expected to
undergo the intramolecular insertion of olefins to give F (path
a). Oxidative addition of the C–Br bond to the Rh(I) center
leads to the formation of seven-membered ring Rh(III) species
H.11 Another possibility for the formation of H via inter-
mediate G must also be considered (path b).12 In the
end, the reductive elimination of H releases product 3 and
regenerates the Rh(I) catalyst.
5
6
2e
2f
4
3
3e
3f
46
70
To further investigate the proposed mechanism,
deuterium-labelled substrate (Z)-2a-d was synthesized and
subjected to the same conditions (eqn (2)). Compound
(cis)-3a-d was isolated and its stereochemistry was assigned
7
2g
2h
3
3g
75
8
7
3
3h
3h
32
55
9b
a
Reaction conditions: 1,6-enyne (0.3 mmol),
Rh(CO)2(acac) (0.03 mmol), PPh3 (0.06 mmol), K2CO3 (0.36 mmol)
1 (0.45 mmol),
b
in dioxane/H2O (20 : 1, 3 mL) at 100 1C. RhOH(COD) (0.03 mmol)
was used. Isolated yield.
c
reaction result. Other bases, such as Na2CO3 and KOH, were
much less efficient than K2CO3 (Table 1, entries 5 and 6). With
regard to the rhodium source, RhCl(COD) and RhCl(PPh3)3
were found to be inert in this transformation (Table 1, entries 8
and 9). However, RhOH(COD), with or without PPh3, was
Scheme 2 The proposed catalytic cycle for the rhodium-catalyzed
[2 + 2 + 2] reaction.
ꢀc
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partner. The reaction involves the Rh-catalyzed regio-
selective insertion of an alkyne into an arylrhodium(I)
species and the oxidative addition of C–Br bonds in the
adjacent phenyl ring to the resulting vinylrhodium(I) species
as key steps. More importantly, the outcome of the deuterium
labelling experiment disclosed that a direct reductive elimination
mechanism dominates over the formation of aryl–Csp3
bonds from aryl-Rh(III)-Csp3 species. Further studies on the
application of the products and the reaction mechanism are
ongoing in our laboratories, and will be reported in
due course.
Notes and references
1 For reviews, see: (a) T. Miura and M. Murakami, Chem. Commun.,
2007, 217; (b) H. C. Guo and J. A. Ma, Angew. Chem., Int. Ed.,
2006, 45, 354; (c) J. C. Wasilke, S. J. Obrey, R. T. Baker and
G. C. Bazan, Chem. Rev., 2005, 105, 1001; (d) J. Montgomery,
Angew. Chem., Int. Ed., 2004, 43, 3890; (e) R. Grigg and
V. Sridharan, J. Organomet. Chem., 1999, 576, 65; (f) E. Negishi,
C. Coperet, S. Ma, S. Y. Liou and F. Liu, Chem. Rev., 1996, 96,
´
365; (g) L. F. Tietze, Chem. Rev., 1996, 96, 115.
2 For recent reviews, see: (a) T. Miura and M. Murakami, Chem.
Commun., 2007, 217; (b) S. W. Youn, Eur. J. Org. Chem., 2009, 16,
2597.
3 (a) R. Shintani, K. Okamoto and T. Hayashi, Chem. Lett., 2005,
34, 1294; (b) T. Matsuda, M. Makino and M. Murakami, Chem.
Lett., 2005, 34, 1416.
Scheme 3 A proposal for the outcome of eqn (2).
as the cis-configuration on the basis of 1H NMR analysis
(see the ESIw).
4 M. Lautens and T. Marquardt, J. Org. Chem., 2004, 69, 4607.
5 M. Miyamoto and N. Chatani, Org. Lett., 2008, 10, 2975.
6 T. Miura and M. Murakami, Org. Lett., 2005, 7, 3339.
7 (a) Y. Harada and N. Chatani, J. Am. Chem. Soc., 2007, 129, 5766;
(b) T. Morimoto and N. Chatani, Org. Lett., 2009, 11, 1777.
8 For reviews, see: (a) A. M. Echavarren and C. Nevado, Chem. Soc.
Rev., 2004, 33, 431; (b) C. Aubert, O. Buisine and M. Malacria,
Chem. Rev., 2002, 102, 813; (c) B. M. Trost, F. D. Toste and
A. B. Pinkerton, Chem. Rev., 2001, 101, 2067.
ð2Þ
9 For the synthesis and utility of similar dihydronaphthalene
derivatives, see: (a) G. Dyker, D. Hildebrandt, J. Liu and
K. Merz, Angew. Chem., Int. Ed., 2003, 42, 4399; (b) N. Asao,
T. Kasahara and Y. Yamamoto, Angew. Chem., Int. Ed., 2003, 42,
3504; (c) A. V. Bedekar, T. Watanabe, K. Tanaka and K. Fuji,
Tetrahedron: Asymmetry, 2002, 13, 721; (d) S. Brown, S. Clarkson,
R. Grigg and V. Sridharan, Tetrahedron Lett., 1993, 34, 157.
10 (a) T. Hayashi, M. Takahashi, Y. Takaya and M. Ogasawara,
J. Am. Chem. Soc., 2002, 124, 5052; (b) P. Zhao and J. F. Hartwig,
J. Am. Chem. Soc., 2007, 129, 1876.
11 (a) Y. Sato, Y. Oonishi and M. Mori, Organometallics, 2003, 22,
30; (b) K. Aikawa, S. Akutagawa and K. Mikami, J. Am. Chem.
Soc., 2006, 128, 12648.
12 (a) R. T. Yu and T. Rovis, J. Am. Chem. Soc., 2006, 128, 2782;
(b) T. Shibata, H. Kurokawa and K. Kanda, J. Org. Chem., 2007,
72, 6521; (c) K. Tanaka, H. Hara, G. Nishida and M. Hirano, Org.
Lett., 2007, 9, 1907.
The outcome of eqn (2) is explained by the proposal outlined
in Scheme 3. In the case of path a, the insertion of the olefin in
E-d proceeds stereospecifically via TS-A to generate alkyl-
Rh(I) intermediate F-d, which is oxidized by C–Br to produce
Rh(III)-intermediate H-d. With regard to path b, similar
chemistry also leads to the formation of H-d via TS-B. Finally,
reductive elimination takes place with retention of stereo-
chemistry to yield product (cis)-3a-d. This means that the
information about the Csp2 stereochemistry can be completely
transferred to the corresponding Csp3 center.13 We believe that
this conclusion will be helpful for enantioselective reactions.
This result also provides strong evidence that the formation of
the aryl–Csp3 bond from the aryl-Rh(III)-Csp3 species proceeds
via a direct reductive elimination mechanism.14
13 L. Jiao and Z.-X. Yu, J. Am. Chem. Soc., 2008, 130, 7178.
14 (a) Y. Wang, P. A. Wender and Z.-X. Yu, J. Am. Chem. Soc., 2007,
129, 10060; (b) B. Bennacer, M. Fujiwara and I. Ojima, Org. Lett.,
2004, 6, 3589; (c) B. Bennacer, M. Fujiwara and I. Ojima, J. Am.
Chem. Soc., 2005, 127, 17756.
In summary, we have realized a new rhodium-catalyzed
[2 + 2 + 2] cycloaddition of a 1,6-enyne with 2-bromo-
phenylboronic acid, which was viewed as one two-component
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 5311–5313 | 5313