Rhodium-Catalyzed asymmetric synthesis of spirocarbocycles: arylboron reagents as surrogates of 1,2-dimetalloarenes

Article abstract of DOI:10.1002/anie.201000937

(Figure Presented) Revolutionary Rh-oad: A rhodium/dienecatalyzed addition of sodium tetraarylborates to alkyne-tethered 2-cydoalken-lones has been developed for the synthesis of splrocarbocycles. The tetraarylborates catalytlcally form two new carbon-carbon bonds. A chlral diene ligand also asymmetrically creates quaternary spirocarbon stereocenters with high enantiomeric purity.

Full text of DOI:10.1002/anie.201000937

Angewandte
Chemie
DOI: 10.1002/anie.201000937
Asymmetric Catalysis
Rhodium-Catalyzed Asymmetric Synthesis of Spirocarbocycles:
Arylboron Reagents as Surrogates of 1,2-Dimetalloarenes**
Ryo Shintani,* Shingo Isobe, Momotaro Takeda, and Tamio Hayashi*
Enantiopure spirocycles that possess a quaternary spirocar-
bon stereocenter[1] represent an important class of com-
pounds as they can be found in various useful organic
molecules, such as natural products,[2] biologically active
compounds,[3] and effective chiral ligands for asymmetric
catalysis.[4] Construction of such spirocycles using transition-
metal-catalyzed asymmetric carbon–carbon bond-forming
reactions are highly desirable in view of the efficiency of the
process.[5] In this context, sequential addition of 1,2-dimetal-
loarenes to 2-cycloalken-1-ones that are tethered at the
3-position to another electrophilic substituent, such as an
alkyne, could rapidly afford spirocarbocycles in a convergent
manner, as illustrated in Scheme 1; however, the preparation
substrate and conducted a reaction with phenylboronic acid
in the presence of [{Rh(OH)(cod)}2] (5 mol% Rh) in aqueous
tetrahydrofuran at 658C.[9] Under these conditions, substrate
1a was fully consumed and the desired spirocycle 3aa was
successfully obtained in 60% yield (Table 1, entry 1). The use
Table 1: Rhodium-catalyzed addition–cyclization of phenylboron
reagents to 3-(4-phenyl-3-butyn-1-yl)-2-cyclohexen-1-one (1a).
Entry
[Rh] catalyst
Ph-[B]
Yield [%][a]
1
[{Rh(OH)(cod)}2]
[{Rh(OH)(cod)}2]
[{RhCl(cod)}2]
PhB(OH)2
PhB(OR)2[c]
Ph4BNa
60
33
2[b]
3
73
4
[{RhCl(binap)}2]
Ph4BNa
<5[d]
[a] Yield of isolated product. [b] The reaction was conducted in the
absence of H2O. [c] (OR)2 =OCH2CMe2CH2O. [d] Determined by
1H NMR analysis of the crude material. cod=1,5-cyclooctadiene,
binap=1,1’-binaphthalene-2,2’-diylbis(diphenylphosphine).
of phenylboronic acid neopentylglycol ester under anhydrous
conditions resulted in lower yield of 3aa (33% yield; Table 1,
entry 2). In contrast, sodium tetraphenylborate (2a),[10] which
was reported by Murakami and co-workers as an effective
nucleophile in a related transformation,[7b] was found to be a
better nucleophile, and gave 3aa in 73% yield under the
catalysis of [{RhCl(cod)}2] in aqueous tetrahydrofuran
(Table 1, entry 3). It is worth noting that the reaction using
2a did not proceed effectively with a rhodium–bis(phosphine)
complex as the catalyst (Table 1, entry 4).
Using sodium tetraphenylborate in the presence of
[{RhCl(cod)}2] catalyst, aryl, alkenyl, and alkyl substituents
were all tolerated on the alkyne group of 3-(2-alkynylethyl)-2-
cyclohexen-1-ones 1 to give the corresponding spirocycles 3
(60–74% yield; Table 2, entries 1–5); 2-cyclopenten-1-one
derivative 1 f was also employed with similar efficiency (77%
yield; Table 2, entry 6).[11] With regard to the nucleophilic
component, (hetero)aryl-substituted tetraarylborates were
effectively incorporated in the reaction (62–77% yield;
Table 2, entries 7–13), and the use of 3-substituted tetraar-
ylborates led to the regioselective formation of a spirocycle at
the less-hindered position (selectivity ꢀ 11:1; Table 2,
entries 10–12).
Scheme 1. Strategy for the convergent synthesis of spirocarbocycles.
and successful use of 1,2-dimetalloarenes is not always
trivial.[6] To circumvent the potential difficulty of this
convergent strategy, we anticipated that an arylrhodation–
1,4-rhodium-migration sequence could be used as a surrogate,
which is a known process in the context of the addition of
arylboron reagents to internal alkynes under rhodium catal-
ysis.[7,8]
To implement the aforementioned strategy, we chose 3-(4-
phenyl-3-butyn-1-yl)-2-cyclohexen-1-one (1a) as a model
[*] Dr. R. Shintani, S. Isobe, M. Takeda, 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: shintani@kuchem.kyoto-u.ac.jp
thayashi@kuchem.kyoto-u.ac.jp
[**] Support has been provided in part by a Grant-in-Aid for Scientific
Research (S; 19105002) from the Ministry of Education, Culture,
Sports, Science, and Technology (Japan).
When
sodium
tetrakis(pentadeuteriophenyl)borate
([D20]-2a) was used as the nucleophile in the reactions with
1a and 1 f, the products obtained (3aa and 3 fa, respectively)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201000937.
Angew. Chem. Int. Ed. 2010, 49, 3795 –3798
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3795

Communications
Table 2: Rhodium-catalyzed addition–cyclization of sodium tetraarylbo-
rates 2 to 3-(2-alkynylethyl)-2-cycloalken-1-ones 1.
of the alkyne group of 1a to give alkenylrhodium intermedi-
ate A.[14] Successive 1,4-rhodium migration gives arylrhodium
species B, which then reacts with the tethered enone moiety,
leading to oxa-p-allylrhodium intermediate C. Hydrolysis of
this intermediate releases product 3aa along with a hydroxo-
rhodium complex, the transmetalation of which with 2a
regenerates the phenylrhodium species to complete the cycle.
We also conducted the reaction of 1a with sodium
tetrakis(2-deuteriophenyl)borate ([D4]-2a) and found that
product 3aa contained 21% deuteration at the olefin carbon
atom and 78% deuterium remained at the aromatic carbon
atom [Eq. (2)]. This result indicates that a primary kinetic
Entry 1 (n; R)
2 (X)
Product Yield [%][a]
1
2
3
4
5
6
7
1a (1; Ph)
2a (H)
2a
2a
3aa
3ba
3ca
3da
3ea
3 fa
3 fb
3 fc
3 fd
3 fe
3 ff
73
70
74
60
64
77
69
77
1b (1; 4-FC6H4)
1c (1; 2-naphthyl)
1d (1; 1-cyclohexenyl)
1e (1; CH2CMe2(OMe)) 2a
1 f (0; Ph)
1 f
1 f
1 f
1 f
1 f
1 f
1 f
2a
2a
2b (4-Me)
2c (4-Cl)
2d (4-F)
2e (3-OMe)
2 f (3-Me)
2g (3-Cl)
2h[g]
8[b]
9
10
72
64[c]
62[d]
70[f]
68[h]
11
12[e]
13
3 fg
3 fh
[a] Yield of isolated product. [b] 35 hours, 7 mol% of catalyst. [c] Regio-
selectivity 3-MeO/5-MeO=11:1. [d] Regioselectivity: 3-Me/5-Me >99:1.
[e] 45 hours, 8 mol% of catalyst. [f] Regioselectivity: 3-Cl/5-Cl=23:1.
[g] 2h: sodium tetrakis(3-thienyl)borate. [h] Regioselectivity: 2,3-fused/
3,4-fused=3:1.
isotope effect (kH/kD = 3.7) is observed in the 1,4-rhodium
migration step (A!B; Scheme 2), and that this step could be
the turnover-limiting step of the catalytic cycle.
Because the step from B to C in Scheme 2 creates a
quaternary carbon stereocenter,[15,16] and the present reaction
is effectively catalyzed by a rhodium–diene complex, we
began to explore the development of its asymmetric variant
using chiral diene ligands.[17–19] As shown in Equation (3), the
use of (R)-L1[15c,20] as the ligand in the reaction of 1a with 2a
showed quantitative deuteration at the olefin carbon, as
shown in Equation (1).[12] On the basis of these results, we
have proposed a catalytic cycle for the reaction between 1a
and 2a (Scheme 2).[7,13] Thus, a phenylrhodium species, which
is initially generated by the transmetalation of a phenyl group
from 2a onto the chlororhodium species, undergoes insertion
gave product 3aa in only 22% yield, although the enantio-
selectivity was relatively high (88% ee). By changing the
ligand to (R,R)-Ph-bod*,[21] 3aa was obtained in somewhat
higher yield and ee value (43% yield, 95% ee), and further
improvement was observed using (R,R)-Bn-bod*,[21] and gave
3aa in 73% yield with 97% ee.
Under the conditions with (R,R)-Bn-bod* as the ligand,
several 3-(2-alkynylethyl)-2-cycloalken-1-ones 1 efficiently
reacted with sodium tetraphenylborate (2a) and gave the
corresponding spirocycles 3 with excellent enantioselectivity
(70–76% yield, 95–97% ee; Table 3, entries 1–4). As well as
2a, some other aryl nucleophiles were also successfully
employed, constructing quaternary spirocarbon stereocenters
with high enantiomeric excess values (55–75% yield, 91–
96% ee; Table 3, entries 5–8). The olefin portion of product
Scheme 2. Proposed catalytic cycle for the rhodium-catalyzed addition–
cyclization of 2a to 1a.
3796 www.angewandte.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 3795 –3798

Angewandte
Chemie
Table 3: Rhodium-catalyzed asymmetric addition–cyclization of sodium
tetraarylborates 2 to 3-(2-alkynylethyl)-2-cycloalken-1-ones 1.
moiety of the enone and the benzyl group on the olefin of
(R,R)-Bn-bod*; this mechanism would lead to the selective
formation of spirocycle 3 with the observed absolute config-
uration.
In summary, we have developed the addition of sodium
tetraarylborates to alkyne-tethered 2-cycloalken-1-ones, cat-
alyzed by a rhodium–diene complex, for the convergent
synthesis of spirocarbocycles. These tetraarylborates function
as surrogates of 1,2-dimetalloarenes, sequentially forming two
new carbon–carbon bonds through the catalytic process. We
have also developed an effective asymmetric variant of the
present catalysis by employing a chiral diene ligand to create
quaternary spirocarbon stereocenters with high enantiomeric
purity.
Entry
1
2
t [h]
Product
Yield [%][a]
ee [%][b]
1
2
3
4
5
6
7
8
1a
1b
1c
1 f
1 f
1 f
1 f
1 f
2a
2a
2a
2a
2b
2c
2d
2 f
20
20
20
20
45
45
45
45
3aa
3ba
3ca
3 fa
3 fb
3 fc
3 fd
3 ff
73
72
70
76
72
71
75
55[c]
97
97
97
95
94
96
96
91
Received: February 15, 2010
Revised: March 13, 2010
Published online: April 15, 2010
[a] Yield of isolated product. [b] Determined by HPLC on a chiral
stationary phase with hexane/2-propanol. [c] Regioselectivity: 3-Me/5-
Me >99:1.
Keywords: asymmetric catalysis · boron · chiral diene · rhodium ·
.
spirocycles
3 fc readily underwent oxidative cleavage with oxone under
ruthenium catalysis[22] and gave spirocyclic diketone 4 with
retention of enantiomeric purity, as illustrated in Equa-
tion (4). The absolute configuration of diketone 4 was
determined to be S by X-ray crystallographic analysis.[23]
[1] For reviews on quaternary stereocenters, see: a) B. M. Trost, C.
Jiang, Synthesis 2006, 369; b) J. Christoffers, A. Baro, Adv. Synth.
Catal. 2005, 347, 1473; c) C. J. Douglas, L. E. Overman, Proc.
Natl. Acad. Sci. USA 2004, 101, 5363; d) I. Denissova, L.
Barriault, Tetrahedron 2003, 59, 10105.
[2] a) G. H. Posner, T. G. Hamill, J. Org. Chem. 1988, 53, 6031;
b) J. R. Hwu, J. M. Wetzel, J. Org. Chem. 1992, 57, 922; c) Y.
Kita, H. Fujioka, Pure Appl. Chem. 2007, 79, 701.
[3] a) Y. Endo, S. Takehana, M. Ohno, P. E. Driedger, S. Stabel,
M. Y. Mizutani, N. Tomioka, A. Itai, K. Shudo, J. Med. Chem.
1998, 41, 1476; b) Z. Xiao, L. S. Kappen, I. H. Goldberg, Bioorg.
Med. Chem. Lett. 2006, 16, 2895.
[4] For reviews, see: a) K. Ding, Z. Han, Z. Wang, Chem. Asian J.
2009, 4, 32; b) J.-H. Xie, Q.-L. Zhou, Acc. Chem. Res. 2008, 41,
581; For leading references, see: c) Y.-Z. Zhang, S.-F. Zhu, L.-X.
Wang, Q.-L. Zhou, Angew. Chem. 2008, 120, 8642; Angew.
Chem. Int. Ed. 2008, 47, 8469; d) Y. Yang, S.-F. Zhu, C.-Y. Zhou,
Q.-L. Zhou, J. Am. Chem. Soc. 2008, 130, 14052; e) W. Shu, Q.
Yu, S. Ma, Adv. Synth. Catal. 2009, 351, 2807; f) T. Tsujihara, K.
Takenaka, K. Onitsuka, M. Hatanaka, H. Sasai, J. Am. Chem.
Soc. 2009, 131, 3452; g) Z. Han, Z. Wang, X. Zhang, K. Ding,
Angew. Chem. 2009, 121, 5449; Angew. Chem. Int. Ed. 2009, 48,
5345.
On the basis of the absolute configuration of 4, the
stereochemical course of the present asymmetric catalysis
with rhodium–(R,R)-Bn-bod* can be explained as shown in
Scheme 3. Thus, during the step from B to C (Scheme 2) two
possible intermediates, I and II, could undergo insertion of
the enone; intermediate I is preferred to II as it would avoid
the unfavorable steric interaction between the carbonyl
[5] For examples of intermolecular reactions, see: a) K. Tsuchi-
kama, Y. Kuwata, T. Shibata, J. Am. Chem. Soc. 2006, 128, 13686;
b) B. M. Trost, N. Cramer, S. M. Silverman, J. Am. Chem. Soc.
2007, 129, 12396; c) M. Ichinose, H. Suematsu, T. Katsuki,
Angew. Chem. 2009, 121, 3167; Angew. Chem. Int. Ed. 2009, 48,
3121; For examples of intramolecular reactions, see: d) Y.
Yamaura, M. Hyakutake, M. Mori, J. Am. Chem. Soc. 1997,
119, 7615; e) A. Ashimori, B. Bachand, L. E. Overman, D. J.
Poon, J. Am. Chem. Soc. 1998, 120, 6477; f) M. Hatano, K.
Mikami, J. Am. Chem. Soc. 2003, 125, 4704; g) A. Wada, K.
Noguchi, M. Hirano, K. Tanaka, Org. Lett. 2007, 9, 1295; See
also: h) X. Teng, D. R. Cefalo, R. R. Schrock, A. H. Hoveyda, J.
Am. Chem. Soc. 2002, 124, 10779; i) E. Zhang, C.-A. Fan, Y.-Q.
Tu, F.-M. Zhang, Y.-L. Song, J. Am. Chem. Soc. 2009, 131, 14626.
[6] a) H. J. S. Winkler, G. Wittig, J. Org. Chem. 1963, 28, 1733;
b) M. A. G. M. Tinga, G. Schat, O. S. Akkerman, F. Bickelhaupt,
E. Hora, H. Kooijman, W. J. J. Smeets, A. L. Spek, J. Am. Chem.
Soc. 1993, 115, 2808; c) M. Amano, A. Saiga, R. Ikegami, T.
Scheme 3. Proposed stereochemical pathway for the formation of
spirocycle 3, catalyzed by Rh/(R,R)-Bn-bod*.
Angew. Chem. Int. Ed. 2010, 49, 3795 –3798
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3797

Communications
Ogata, K. Takagi, Tetrahedron Lett. 1998, 39, 8667; d) A. B.
2007, 1279; b) T. Hayashi, Bull. Chem. Soc. Jpn. 2004, 77, 13;
c) T. Hayashi, K. Yamasaki, Chem. Rev. 2003, 103, 2829; d) K.
Fagnou, M. Lautens, Chem. Rev. 2003, 103, 169; e) C. Bolm, J. P.
Hildebrand, K. Muꢂiz, N. Hermanns, Angew. Chem. 2001, 113,
3382; Angew. Chem. Int. Ed. 2001, 40, 3284.
Evnin, D. Seyferth, J. Am. Chem. Soc. 1967, 89, 952; e) R.
Altmann, K. Jurkschat, M. Schꢀrmann, Organometallics 1998,
17, 5858; f) A. B. Chopa, M. T. Lockhart, G. F. Silbestri, Organo-
metallics 2002, 21, 5874; g) H. Yoshida, K. Tanino, J. Ohshita, A.
Kunai, Angew. Chem. 2004, 116, 5162; Angew. Chem. Int. Ed.
2004, 43, 5052; h) K. Nozaki, M. Yoshida, H. Takaya, Bull.
Chem. Soc. Jpn. 1996, 69, 2043; i) M. Shimizu, I. Nagao, Y.
Tomioka, T. Hiyama, Angew. Chem. 2008, 120, 8216; Angew.
Chem. Int. Ed. 2008, 47, 8096; j) H. Noguchi, T. Shioda, C.-M.
Chou, M. Suginome, Org. Lett. 2008, 10, 377; k) H. Ihara, M.
Suginome, J. Am. Chem. Soc. 2009, 131, 7502; l) H. Yoshida, J.
Ikadai, M. Shudo, J. Ohshita, A. Kunai, J. Am. Chem. Soc. 2003,
125, 6638; m) A. Kawachi, A. Tani, K. Machida, Y. Yamamoto,
Organometallics 2007, 26, 4697.
[14] Insertion of an alkyne to arylrhodium species that have a diene
ligand is known to be more facile than that of an electron-
deficient olefin. See Ref. [9g].
[15] For examples of rhodium-catalyzed asymmetric 1,4-additions to
create quaternary carbon stereocenters, see: a) P. Mauleꢃn, J. C.
Carretero, Chem. Commun. 2005, 4961; b) R. Shintani, W.-L.
Duan, T. Hayashi, J. Am. Chem. Soc. 2006, 128, 5628; c) R.
Shintani, Y. Tsutsumi, M. Nagaosa, T. Nishimura, T. Hayashi, J.
Am. Chem. Soc. 2009, 131, 13588.
[16] For examples of copper catalysis, see: a) J. Wu, D. M. Mam-
preian, A. H. Hoveyda, J. Am. Chem. Soc. 2005, 127, 4584; b) E.
Fillion, A. Wilsily, J. Am. Chem. Soc. 2006, 128, 2774; c) D.
Martin, S. Kehrli, M. dꢄAugustin, H. Clavier, M. Mauduit, A.
Alexakis, J. Am. Chem. Soc. 2006, 128, 8416; d) M. dꢄAugustin,
L. Palais, A. Alexakis, Angew. Chem. 2005, 117, 1400; Angew.
Chem. Int. Ed. 2005, 44, 1376; e) T. L. May, M. K. Brown, A. H.
Hoveyda, Angew. Chem. 2008, 120, 7468; Angew. Chem. Int. Ed.
2008, 47, 7358; f) K. M. Brown, A. H. Hoveyda, J. Am. Chem.
Soc. 2008, 130, 12904.
[7] a) T. Hayashi, K. Inoue, N. Taniguchi, M. Ogasawara, J. Am.
Chem. Soc. 2001, 123, 9918; b) T. Miura, T. Sasaki, H. Nakazawa,
M. Murakami, J. Am. Chem. Soc. 2005, 127, 1390; c) R. Shintani,
K. Takatsu, T. Hayashi, Angew. Chem. 2007, 119, 3809; Angew.
Chem. Int. Ed. 2007, 46, 3735; See also: d) K. Oguma, M. Miura,
T. Satoh, M. Nomura, J. Am. Chem. Soc. 2000, 122, 10464; e) R.
Shintani, K. Okamoto, T. Hayashi, J. Am. Chem. Soc. 2005, 127,
2872; f) H. Yamabe, A. Mizuno, H. Kusama, N. Iwasawa, J. Am.
Chem. Soc. 2005, 127, 3248; g) T. Matsuda, M. Shigeno, M.
Murakami, J. Am. Chem. Soc. 2007, 129, 12086; h) M. Shigeno, T.
Yamamoto, M. Murakami, Chem. Eur. J. 2009, 15, 12929; i) T.
Seiser, O. A. Roth, N. Cramer, Angew. Chem. 2009, 121, 6438;
Angew. Chem. Int. Ed. 2009, 48, 6320.
[17] For reviews on chiral dienes, see: a) R. Shintani, T. Hayashi,
Aldrichimica Acta 2009, 42, 31; b) C. Defieber, H. Grꢀtzmacher,
E. M. Carreira, Angew. Chem. 2008, 120, 4558; Angew. Chem.
Int. Ed. 2008, 47, 4482.
[8] For examples of palladium-catalyzed transformations involving
a 1,4-palladium migration, see: a) M. A. Campo, R. C. Larock, J.
Am. Chem. Soc. 2002, 124, 14326; b) M. A. Campo, Q. Huang, T.
Yao, Q. Tian, R. C. Larock, J. Am. Chem. Soc. 2003, 125, 11506;
c) Q. Huang, M. A. Campo, T. Yao, Q. Tian, R. C. Larock, J. Org.
Chem. 2004, 69, 8251; d) J. Zhao, R. C. Larock, Org. Lett. 2005, 7,
701.
[9] For reviews on rhodium-catalyzed arylative cyclization reactions
of alkyne-tethered electrophiles, see: a) T. Miura, M. Murakami,
Chem. Commun. 2007, 217; b) S. W. Youn, Eur. J. Org. Chem.
2009, 2597; For leading references, see: c) T. Miura, M. Shimada,
M. Murakami, J. Am. Chem. Soc. 2005, 127, 1094; d) T. Miura, T.
Sasaki, T. Harumashi, M. Murakami, J. Am. Chem. Soc. 2006,
128, 2516; e) T. Miura, K. Ueda, Y. Takahashi, M. Murakami,
Chem. Commun. 2008, 5366; f) R. Shintani, K. Okamoto, Y.
Otomaru, K. Ueyama, T. Hayashi, J. Am. Chem. Soc. 2005, 127,
54; g) R. Shintani, A. Tsurusaki, K. Okamoto, T. Hayashi,
Angew. Chem. 2005, 117, 3977; Angew. Chem. Int. Ed. 2005, 44,
3909; h) Y. Chen, C. Lee, J. Am. Chem. Soc. 2006, 128, 15598;
See also: i) D. F. Cauble, J. D. Gipson, M. J. Krische, J. Am.
Chem. Soc. 2003, 125, 1110; j) M. Lautens, T. Marquardt, J. Org.
Chem. 2004, 69, 4607; k) M. Miyamoto, Y. Harada, M. Tobisu, N.
Chatani, Org. Lett. 2008, 10, 2975.
[18] For examples of asymmetric reactions using chiral diene ligands,
see: a) C. Fischer, C. Defieber, T. Suzuki, E. M. Carreira, J. Am.
Chem. Soc. 2004, 126, 1628; b) J.-F. Paquin, C. Defieber, C. R. J.
Stephenson, E. M. Carreira, J. Am. Chem. Soc. 2005, 127, 10850;
c) F. Lꢅng, F. Breher, D. Stein, H. Grꢀtzmacher, Organometallics
2005, 24, 2997; d) S. Helbig, S. Sauer, N. Cramer, S. Laschat, A.
Baro, W. Frey, Adv. Synth. Catal. 2007, 349, 2331; e) Z.-Q. Wang,
C.-G. Feng, M.-H. Xu, G.-Q. Lin, J. Am. Chem. Soc. 2007, 129,
5336; f) T. Noꢆl, K. Vandyck, J. Van der Eycken, Tetrahedron
2007, 63, 12961; g) T. Gendrineau, O. Chuzel, H. Eijsberg, J.-P.
Genet, S. Darses, Angew. Chem. 2008, 120, 7783; Angew. Chem.
Int. Ed. 2008, 47, 7669; h) X. Hu, M. Zhuang, Z. Cao, H. Du,
Org. Lett. 2009, 11, 4744; i) M. K. Brwon, E. J. Corey, Org. Lett.
2010, 12, 172.
[19] a) T. Hayashi, K. Ueyama, N. Tokunaga, K. Yoshida, J. Am.
Chem. Soc. 2003, 125, 11508; b) Y. Otomaru, A. Kina, R.
Shintani, T. Hayashi, Tetrahedron: Asymmetry 2005, 16, 1673;
c) A. Kina, K. Ueyama, T. Hayashi, Org. Lett. 2005, 7, 5889;
d) R. Shintani, Y. Ichikawa, K. Takatsu, F.-X. Chen, T. Hayashi,
J. Org. Chem. 2009, 74, 869; e) T. Nishimura, H. Kumamoto, M.
Nagaosa, T. Hayashi, Chem. Commun. 2009, 5713.
[20] K. Okamoto, T. Hayashi, V. H. Rawal, Chem. Commun. 2009,
4815.
[10] a) M. Ueda, N. Miyaura, J. Organomet. Chem. 2000, 595, 31;
b) K. Ueura, S. Miyamura, T. Satoh, M. Miura, J. Organomet.
Chem. 2006, 691, 2821.
[11] The use of alkene-tethered enone 3-(4-phenyl-3-buten-1-yl)-2-
cyclohexen-1-one as a substrate results in a messy reaction with
approximately 40% recovery of the substrate.
[12] kH/kD = 1.04 was observed when the reaction of 1a was
conducted with an equimolar mixture of 2a and [D20]-2a.
[13] For reviews on rhodium-catalyzed 1,4-addition reactions, see:
a) J. Christoffers, G. Koripelly, A. Rosiak, M. Rꢁssle, Synthesis
[21] 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.
[22] D. Yang, C. Zhang, J. Org. Chem. 2001, 66, 4814.
[23] CCDC 764834 (4) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif.
3798
www.angewandte.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 3795 –3798