Highly chemo- and enantioselective arylative cyclization of alkyne-tethered electron-deficient olefins catalyzed by rhodium complexes with chiral dienes

Article abstract of DOI:10.1002/anie.200500843

(Chemical Equation Presented) A rhodium catalyst promotes the arylative cyclization of alkyne-tethered electron-deficient olefins in the presence of aryl boronic acids. High chemoselectivity was attained uniquely by the use of diene ligands, and high enan

Full text of DOI:10.1002/anie.200500843

Angewandte
Chemie
Asymmetric Catalysis
Highly Chemo- and Enantioselective Arylative
Cyclization of Alkyne-Tethered Electron-
Deficient Olefins Catalyzed by Rhodium
Complexes with Chiral Dienes**
Ryo Shintani, Akihiro Tsurusaki, Kazuhiro Okamoto,
and Tamio Hayashi*
Multiple carbon–carbon bond-forming reactions catalyzed by
transition metals are a powerful method for the construction
of structurally complex molecules in a convergent manner
from relatively simple precursors.[1] Compounds that bear two
or more electrophilic sites at appropriate positions are
potentially useful for the preparation of complex cyclic
materials by sequential addition and cyclization of nucleo-
philes in a cascade manner.[2,3] However, if these electrophilic
sites are all reactive toward the incoming nucleophile,
chemoselectivity of the initial nucleophilic attack becomes
an important issue. In this context, alkyne-tethered electron-
deficient olefins should be an interesting class of substrates, as
both internal alkynes[4] and electron-deficient olefins[5] are
good electrophiles in a rhodium–bisphosphine-catalyzed
addition of aryl boronic acids [Eq. (1) and Eq. (2); EWG =
electron-withdrawing group]. Herein, we describe how a
rhodium–diene catalyst, rather than a rhodium–bisphosphine
catalyst, can effectively catalyze an arylative cyclization of
alkyne-tethered electron-deficient olefins with high chemo-
selectivity, and that high enantioselectivity can also be
attained by the use of chiral diene ligands in this process
(Scheme 1).
In an initial investigation, we employed alkyne-tethered
enoate 1a as a model substrate in combination with
PhB(OH)2 to examine the effect of the ligand in the presence
of 6 mol% rhodium (Table 1). Although the reaction pro-
ceeds smoothly when (S)-binap is used as a ligand, a mixture
[*] Dr. R. Shintani, A. Tsurusaki, K. Okamoto, Prof. Dr. T. Hayashi
Department of Chemistry
Graduate School of Science
Kyoto University
Sakyo, Kyoto 606-8502 (Japan)
Fax: (+81)75-753-3988
E-mail: thayashi@kuchem.kyoto-u.ac.jp
[**] Support was provided in part by a grant-in-aid for scientific research
by the Ministry of Education, Culture, Sports, Science, and
Technology, Japan (21 COE on Kyoto University Alliance for
Chemistry).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2005, 44, 3909 –3912
DOI: 10.1002/anie.200500843
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3909

Communications
Table 2: Rhodium-catalyzed arylative cyclization: scope of substrate 1.[a]
Entry Substrate R; EWG
Yield [%][b] ee [%][c] [a]D20 (in CHCl3)
1
2
3
4
1a
1b
1c
1d
Et; CO2Me 93
Me; CO2Me 86
99
99
99
90
À65.8 (c=0.97)
À67.0 (c=0.97)
À73.5 (c=1.02)
À90.2 (c=1.45)
Et; CO2Et
Et; COPh
89
87
[a] Conditions: [{RhCl(C2H4)2}2] (6 mol% Rh), (S,S)-Bn-bod*
(6.5 mol%), KOH (0.3 equiv), dioxane/H2O (10:1), 608C, 4 h. [b] Con-
taminated with up to 10% of 3 and 4 (ꢀ1:1) in all cases. [c] ee values
were determined by HPLC on a chiralpak AD-H column.
Scheme 1. a) [{RhCl(C2H4)2}2] (6 mol% Rh), (S,S)-Bn-bod* (6.5 mol%),
KOH (0.3 equiv), dioxane/H2O (10:1), 608C, 4 h.
Table 1: Rhodium-catalyzed asymmetric arylative cyclization of model
substrate 1a: effect of the ligand.[a]
Yield [%]
on the olefin to furnish five-membered carbocycles with high
chemo- and enantioselectivities (90–99% ee).
With respect to the scope of the nucleophilic component,
sterically and electronically diverse arrays of aryl boronic
acids can be used under the same conditions to afford the five-
membered products uniformly with high chemoselectivity
and with excellent enantioselectivity (Table 3; 97–99% ee).
(S)-binap
dppf
(S,S)-Bn-bod*
cod
23 (95% ee)
22
9
5
45
32
5
3
83 (99% ee)
72
Table 3: Rhodium-catalyzed asymmetric arylative cyclization: scope of
3
8
the aryl boronic acid.[a]
[a] Conditions: [{RhCl(C2H4)2}2] (6 mol% Rh), ligand (6.5 mol%), KOH
(0.3 equiv), dioxane/H2O (10:1), 608C, 4 h. (S)-binap=2,2’-bis(diphe-
nylphosphino)-1,1’-binaphthyl, dppf=1,1’-bis(diphenylphosphino)ferro-
cene, cod=cycloocta-1,5-diene.
Entry
Ar
Yield [%][b]
ee [%][c]
[a]2D0 (in CHCl3)
1
2
3
4
5
6
7
Ph
93
87
86
88
84
83
80
99
99
99
97
99
99
98
À65.8 (c=0.97)
À87.7 (c=1.11)
À90.9 (c=1.14)
À72.5 (c=1.28)
À77.4 (c=1.29)
À63.5 (c=1.07)
À82.8 (c=0.94)
4-MeC6H4
4-MeOC6H4
4-FC6H4
3-ClC6H4
3,5-Me2C6H3
2-naphthyl
of three different phenylated products (2a, 3a,[6] and 4a) are
obtained rather nonselectively (23, 22, and 45% yields,
respectively). The use of other bisphosphine ligands such as
dppf leads to somewhat lower reactivity (51% conversion),
which tends to give 1,4-adduct 4a as the major product. In
contrast, the use of chiral diene ligand (S,S)-Bn-bod*[2f,7]
dramatically changes the course of the reaction and prefer-
entially leads to product 2a, which is obtained in 83% yield
and with 99% ee (compare with 95% ee when (S)-binap is
used), with a small amount of 3a and 4a (5% yield for each)
also formed. The employment of other diene ligands such as
cod also provides compound 2a as the major product.
[a] Conditions: [{RhCl(C2H4)2}2] (6 mol% Rh), (S,S)-Bn-bod*
(6.5 mol%), KOH (0.3 equiv), dioxane/H2O (10:1), 608C, 4 h. [b]
Contaminated with 7–11% of 3/4 (ꢀ1:1) in all cases. [c] ee values
were determined by HPLC on a Chiralpak AD-H column.
To gain insight into the origin of the difference in
chemoselectivity between rhodium–bisphosphine and rho-
dium–diene catalysts in these arylative cyclization reactions,
we conducted the following experiments. Reaction of a,b-
enoate 5 with an aryl boronic acid (Ar= 3,5-Me2C6H3) in the
presence of 6 mol% Rh–(S)-binap produced the correspond-
ing 1,4-adduct 6 in 76% yield (Scheme 2). In contrast, the use
of alkyne 7 as a substrate under Rh–(S)-binap catalysis
resulted in 94% recovery of 7 with almost no formation of
Under these conditions with Rh(S,S)-Bn-bod* as a
catalyst, several alkyne-tethered electron-deficient olefins
can be successfully used as shown in Table 2. Thus, not only
methyl or ethyl esters (entries 1–3) but also phenyl ketone
(entry 4) can be employed as an electron-withdrawing group
3910
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Angewandte
Chemie
in the arylation of alkynes than in the 1,4-addition of a,b-
enoates. This conclusion should partially explain the observed
high chemoselectivity in the arylative cyclization of 1 with a
rhodium–diene catalyst.[8]
In summary, we have developed a rhodium-catalyzed
arylative cyclization of alkyne-tethered electron-deficient
olefins with aryl boronic acids, and high chemo- and
enantioselectivities have been observed by the use of a
chiral diene ligand. We hope to further develop chiral diene
ligands and their application to various transition-metal-
catalyzed asymmetric processes.
Scheme 2. a) [{RhCl(C2H4)2}2] (6 mol% Rh), (S)-binap (6.5 mol%),
KOH (0.3 equiv), dioxane/H2O (10:1), 608C, 4 h.
arylated product 8 (Scheme 3). Compared to these results,
both a,b-enoate 5 and alkyne 7 reacted with the aryl boronic
acid (Ar= 3,5-Me2C6H3) in the presence of 6 mol% Rh–cod
Experimental Section
Procedure for Table 1: An aqueous solution of KOH (0.3m in H2O;
0.2 mL, 60 mmol) was added to a solution of [{RhCl(C2H4)2}2] (2.3 mg,
12 mmol Rh) and ligand (13 mmol) in 1,4-dioxane (1.0 mL), and the
mixture was stirred for 5 min at room temperature. PhB(OH)2
(85.4 mg, 0.70 mmol) and 1a (59.3 mg, 0.20 mmol) were then added
along with additional 1,4-dioxane (1.0 mL), and the resulting solution
was stirred for 4 h at 608C. The reaction mixture was directly passed
through a pad of silica gel with Et2O, and the solvent was removed
under vacuum. The residue was purified by preparative TLC (silica
gel) with a mixture of Et2O/hexane (1:1) as eluent.
With (S)-binap as ligand, a mixture of 2a, 3a, and 4a (26:24:50, as
determined by 1H NMR spectroscopy) was obtained as a pale yellow
oil (67.7 mg, 90% combined yield). The ee value for 2a was
determined on a Daicel Chiralpak AD-H column with hexane/2-
propanol (90:10) and a flow rate of 0.3 mLminÀ1. Retention times:
29.8 min ((+)-enantiomer) and 33.5 min ((À)-enantiomer, 95% ee).
With (S,S)-Bn-bod* as ligand, a mixture of 2a, 3a, and 4a (90:5:5,
as determined by 1H NMR spectroscopy) was obtained as a yellow oil
(69.5 mg, 93% combined yield). 2a: 99% ee; [a]2D0 = À65.8 (c = 0.97,
CHCl3).
Scheme 3. a) [{RhCl(C2H4)2}2] (6 mol% Rh), (S)-binap (6.5 mol%),
KOH (0.3 equiv), dioxane/H2O (10:1), 608C, 4 h.
catalyst to furnish the corresponding arylated products 6 and
8 in over 80% yield (Scheme 4 and Scheme 5). To distinguish
the reactivity between the two, we conducted a competition
Received: March 7, 2005
Published online: May 18, 2005
Scheme 4. a) [{RhCl(cod)}2] (6 mol% Rh), KOH (0.3 equiv), dioxane/
H2O (10:1), 608C, 4 h.
Keywords: asymmetric catalysis · chemoselectivity · cyclization ·
.
diene ligands · rhodium
Scheme 5. a) [{RhCl(cod)}2] (6 mol% Rh), KOH (0.3 equiv), dioxane/
H2O (10:1), 608C, 4 h.
[1] For reviews, see: a) J. Montgomery, Angew. Chem. 2004, 116,
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[2] For examples of rhodium-catalyzed processes, see: a) D. F.
Cauble, J. D. Gipson, M. J. Krische, J. Am. Chem. Soc. 2003,
125, 1110; b) B. M. Bocknack, L.-C. Wang, M. J. Krische, Proc.
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Miura, T. Sasaki, H. Nakazawa, M. Murakami, J. Am. Chem. Soc.
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cyclizations, see: i) T.-G. Baik, A. L. Luis, L.-C. Wang, M. J.
Krische, J. Am. Chem. Soc. 2001, 123, 5112.
experiment using a 1:1 mixture of 5 and 7 with 1.1 equivalents
of aryl boron species (Ar= 3,5-Me2C6H3) in the presence of
6 mol% Rh–cod (Scheme 6). Under these conditions, a,b-
enoate 5 was recovered in 90% yield and alkyne 7 was
completely comsumed to give product 8 in 76% yield. These
results indicate that a Rh–bisphosphine catalyzes the 1,4-
addition of a,b-enoates more effectively than the arylation of
alkynes, and that a Rh–diene catalyst displays higher activity
Scheme 6. a) [{RhCl(cod)}2] (6 mol% Rh), KOH (0.3 equiv), dioxane/
H2O (10:1), 608C, 4 h.
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Communications
[3] For an overview, see: a) J. Montgomery, Acc. Chem. Res. 2000, 33,
[6] Compound 3a is presumably formed through a pathway similar to
that reported in ref. [2h].
[7] a) N. Tokunaga, Y. Otomaru, K. Okamoto, K. Ueyama, R.
Shintani, T. Hayashi, J. Am. Chem. Soc. 2004, 126, 13584; b) Y.
Otomaru, K. Okamoto, R. Shintani, T. Hayashi, J. Org. Chem.
2005, 70, 2503.
[8] This conclusion does not necessarily fully explain the low
chemoselectivity in the reaction of 1a with phenylboronic acid
in the presence of a Rh–bisphosphine catalyst (Table 1).
467; b) R. A. Widenhoefer, Acc. Chem. Res. 2002, 35, 905; c) H.-
Y. Jang, M. J. Krische, Acc. Chem. Res. 2004, 37, 653.
[4] T. Hayashi, K. Inoue, N. Taniguchi, M. Ogasawara, J. Am. Chem.
Soc. 2001, 123, 9918.
[5] a) M. Sakai, H. Hayashi, N. Miyaura, Organometallics 1997, 16,
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3912
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