Allylic substitution of meso-1,4-diacetoxycycloalkenes in water with an amphiphilic resin-supported chiral palladium complex

Article abstract of DOI:10.1055/s-2008-1078422

Asymmetric π-allylic substitution of meso-1,4-diacet-oxycyclopentene and meso-1,4-diacetoxycyclohexene with various nucleophiles was performed with an amphiphilic polystyrene-polyethylene glycol) (PS-PEG) resin-supported chiral imidazoin-dolephosphine-palladium complex in water as a single reaction medium under heterogeneous conditions to give the corresponding 1-acetoxy-4-substituted cycloalkenes with up to 99% ee.

Full text of DOI:10.1055/s-2008-1078422

CLUSTER
1557
Allylic Substitution of meso-1,4-Diacetoxycycloalkenes in Water
with an Amphiphilic Resin-Supported Chiral Palladium Complex
A
llylic Substitutio
a
n of
m
eso-1
s
,4-Diacet
u
oxycycloalke
h
nes iro Uozumi,* Hiroe Takenaka, Toshimasa Suzuka
Institute for Molecular Science (IMS) and CREST, Higashiyama 5-1, Myodaiji, Okazaki 444-8787, Japan
Fax +81(564)595574; E-mail: uo@ims.ac.jp
Received 11 January 2008
Abstract: Asymmetric p-allylic substitution of meso-1,4-diacet-
Pd*
Y
Y
Nu
oxycyclopentene and meso-1,4-diacetoxycyclohexene with various
nucleophiles was performed with an amphiphilic polystyrene-
poly(ethylene glycol) (PS-PEG) resin-supported chiral imidazoin-
dolephosphine-palladium complex in water as a single reaction me-
dium under heterogeneous conditions to give the corresponding 1-
acetoxy-4-substituted cycloalkenes with up to 99% ee.
+ NuH
base
X
X
X
in H2O
racemic
90–99% ee
PS-
PEG
step A
step B
Key words: p-allylpalladium, asymmetric catalysis, aqueous me-
dia, polymer support, palladium catalyst
Pd*
:Nu
Nu:
X
The catalytic asymmetric functionalization of carbon
frameworks has become an important goal in modern syn-
thetic organic chemistry. However, aqueous- and hetero-
geneous-switching of a given organic transformation is
rapidly gaining importance for its ability to provide safe
and green chemical processes.1–5 If asymmetric catalysis
X = CH2, C2H4, NCOOt-Bu
NuH = CH2(COOEt)2, HNBn2, HOC6H4O(4-Me)
step A: formation of the π-allylpalladium intermediate,
step B: enantio-position selective nucleophilic attack
Scheme 1 Asymmetric p-allylic substitution via enantioselective
can be achieved in water with immobilized chiral cata- nucleophilic attack (representative example of previous work)
lysts, the reaction would become what many consider an
ideal organic transformation. We have recently developed
amphiphilic polystyrene-poly(ethylene glycol) (PS-PEG)
Pd*
X
X
resin-supported chiral phosphine-palladium complexes
which promote the asymmetric allylic substitution of a ra-
cemic mixture of allylic esters with various nucleophiles
in water under heterogeneous conditions with excellent
enantioselectivity.6 Thus, for example, the asymmetric al-
lylic substitution of a racemic mixture of cycloalkenyl
carbonate with carbon, nitrogen, or oxygen nucleophiles
was catalyzed by the amphiphilic PS-PEG resin-support-
ed chiral palladium complex 1 in water to give the corre-
sponding cycloalkenyl malonates, amines, or aryl ethers,
respectively, with enantioselectivities of 90–99% ee,
where the reactions proceeded via formation of the p-al-
lylpalladium intermediates and subsequent enantioposi-
tion-selective nucleophilic attack (Scheme 1). Our
continuing interest in the utility of the polymeric chiral
catalyst under aqueous conditions led us to study its po-
tential in the enantioselective desymmetrization of meso-
cycloalkene-1,4-diesters where the stereoselectivity
should be induced mainly at the p-allylic formation step
via the enantioposition-selective oxidative addition
(Scheme 2).7,8
+ NuH
Y
Y
Nu
Y
base
in H2O
meso
step B
Pd*
Pd*
step A
:Nu
X
X
PS-
PEG
PS-
PEG
Y
Y
Pd*
Pd*
step A: enantio-position selective formation
of the π-allylpalladium intermediate,
step B: nucleophilic attack
Scheme 2 Asymmetric p-allylic substitution via enantioselective p-
allylpalladium formation (working hypothesis of the present work)
Here we wish to report preliminary results on the aquacat-
alytic asymmetric desymmetrization of the meso-cy-
cloalkenyl-1,4-diacetate via p-allylic substitution with
carbon, nitrogen, and oxygen nucleophiles, which was
promoted by the palladium complex anchored onto the
amphiphilic PS-PEG resin-supported (3R,9aS)-[2-aryl-3-
(2-diphenylphosphino)phenyl]tetrahydro-1H-imida-
zo[1,5-a]indol-1-one in water under heterogeneous condi-
tions to give the corresponding hemi-substituted products
with up to 99% ee.
SYNLETT 2008, No. 10, pp 1557–1561
x
x
.x
x
.2
0
0
8
Advanced online publication: 16.05.2008
DOI: 10.1055/s-2008-1078422; Art ID: Y00308ST
© Georg Thieme Verlag Stuttgart · New York

1558
Y. Uozumi et al.
CLUSTER
95% enantiomeric purities, respectively (entries 5–7).
Sterically hindered 2,6-dimethylphenol (e) gave 90% ee
of 6e in 59% yield under similar conditions (entry 8). The
reactions with 3-methoxyphenol (f) and 4-tert-butylphe-
nol (g) also gave the desired hemiethers 6f and 6g in 43
and 52% isolated yields with 96 and 94% ee values, re-
spectively (entries 9 and 10). The cyclohexenyl ester
meso-3 also underwent etherification with phenol to give
95% ee of 7 in 37% yield (entry 11).
Pd*
1
(5 mol% Pd)
X
X
AcO
OAc
+ NuH
Nu
OAc
Cs2CO3 in H2O
meso-2 (X = CH2)
meso-3 (X = CH2CH2)
4–7
4: X = CH2, Nu = CH(COOEt)2
5: X = CH2, Nu = N(CH2Ph)2
6: X = CH2, Nu = OAr (a–g)
7: X = CH2CH2, Nu = OPh
X
Nu
Nu
In the asymmetric etherification of meso-2 with phenol (a)
it was found that the enantiomeric purity of the hemiether
6a was dependent on the yield of the disubstituted product
8 (Scheme 4). Thus, in order to decrease the formation of
the diether 8, the asymmetric etherification was carried
out with a fivefold excess of meso-2 at 25 °C to give the
hemiether 6a and the diether 8 in 72% and 5% yields, re-
8
Scheme 3
The aquacatalytic asymmetric desymmetrization of the
meso-cycloalkene-1,4-diesters via p-allylic substitution
was examined for alkylation and amination of cis-1,4-di-
acetoxycyclopentene (meso-2) (Table 1, entries 1 and 2).
Thus, a mixture of the cyclopentene diacetate meso-2 and
diethyl malonate (1.0 equiv to 2) in water was shaken at
0 °C for 18 hours in the presence of 5 mol% palladium of
the amphiphilic resin-supported chiral imidazoindole-
phosphine-palladium complex 1 (average diameter = ca.
100 mm, Pd loading = 0.28 mmol/g, 1% DVB cross-
linked)9 and cesium carbonate as base (entry 1).10 The re-
action mixture was filtered and the resin beads were
rinsed with a small portion of ethyl acetate. The combined
extract was concentrated and the resulting crude residue
was chromatographed on silica gel to give 56% isolated
yield of the hemialkylated product (1R,4S)-4 along with
the dialkylated product 8 (4%).11 We were pleased to find
that the enantiomeric purity of (1R,4S)-4 was 91% ee as
determined by GC analysis using a chiral stationary phase
column (Cyclodex CB). Amination of meso-2 was carried
out with dibenzylamine (2 equiv) in water at 0 °C for 18
hours to give 91% ee of the hemiaminated 5 in 62% iso-
lated yield (entry 2).
Table 1 Asymmetric p-Allylic Substitution of meso-1,4-Diacet-
oxycycloalkenes in Watera,14
Entry
1
Product
Yield (%)b ee (%)
4
56
91
EtO2C
(8: 4%)
OAc
OAc
EtO2C
Ph
2c
5
62
91
(8: –d)
N
Ph
6a–g
6a
6a
6b
6c
6d
6e
6f
ArO
OAc
3
4
Ar = Ph
(at 0 °C)
64
(8: 14%)
99
98
97
94
95
90
96
94
95
Ar = Ph
(at 25 °C)
55
(8: 12%)
5
Ar = 2-BnOC6H4
Ar = 2-ClC6H4
Ar = 2-BrC6H4
45
(8: –d)
With this highly enantioselective desymmetrization pro-
tocol in hand, we turned our attention to demonstrating the
catalytic as well as stereoselective potential of the asym-
metric aquacatalysis in the hemietherification of the
meso-diacetate 2 with phenolic nucleophiles. Though
quite a few reports on the palladium-catalyzed asymmet-
ric p-allylic hemi-substitution of meso-cyclic 1,4-diesters
with carbon and nitrogen nucleophiles have appeared so
far, research on the asymmetric hemietherification with
oxygen nucleophiles has been limited to isolated reports,12
and therefore still remains a challenging target. The reac-
tion of 1,4-diacetoxycyclopentene, meso-2, with phenol
as a nucleophile under similar water-based conditions at
0 °C gave 99% ee of 6a in 64% isolated yield where the
disubstituted product 8 was obtained in 14% yield
(Table 1, entry 3).13 The enantiomeric excess of the phe-
nol ether 6a was slightly decreased (98% ee) when the re-
action was carried out at 25 °C (entry 4). The
etherification took place smoothly in water at 25 °C with
phenols bearing ortho substituents. Thus, 2-benzyloxy-
phenol (b), 2-chlorophenol (c), and 2-bromophenol (d) re-
acted with meso-2 to afford the corresponding hemiethers
6b, 6c, and 6d in 45, 52, and 53% yields with 97, 94, and
6
52
(8: 17%)
7
53
(8: 16%)
8
Ar = 2,6-diMeC6H3
Ar = 3-MeOC6H4
Ar = 4-t-BuC6H4
59
(8: 4%)
9
43
(8: 14%)
10
11
6g
7
52
(8: 11%)
37
(8: 11%)
O
OAc
a All reactions were carried out in H2O at 0 °C for 18 h (entries 1–3)
or 25 °C for 6 h (entries 4–11) with 5 mol% Pd of 1. The ratio of 2 (or
3) (mol)/nucleophile (mol)/Pd (mol)/Cs2CO3 (mol)/H2O (L) =
1:1.0:0.05:0.9:1.0, unless otherwise noted.
b Isolated yield.
c Reaction was carried out with amine (2 equiv) without Cs2CO3.
d Not isolated.
Synlett 2008, No. 10, 1557–1561 © Thieme Stuttgart · New York

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Allylic Substitution of meso-1,4-Diacetoxycycloalkenes
1559
spectively, where the enantiomeric purity of 6a was 84%
ee. The reaction with meso-2 and phenol in an equimolar
ratio gave 98% ee of 6a in 55% yield along with 12% of
8. A similar trend was also observed at 0 °C; the reaction
in a 1:1 mol ratio of meso-2/phenol gave 6a in 64% yield
(99% ee) and 8 (14%), and that in a 5:1 mol ratio gave 6a
in 72% yield (93% ee) and 8 (5%). Though the detailed ki-
netic study on asymmetric induction steps is not clear be-
cause of the complication of the side reactions (e.g.,
hydrolysis of acetate, oxidative addition of allyl phenyl
ether), the kinetic resolution at the second etherification
forming 8, preferentially via ent-6, must contribute to the
increase of the enantiomeric excess of the hemiether 6a
(Scheme 5).
Acknowledgment
This work was supported by the CREST program, sponsored by the
JST. We also thank the MEXT (Scientific Research on Priority Are-
as, No. 460) for partial financial support of this work.
References and Notes
(1) For reviews on aqueous-switching of organic
transformations, see: (a) Li, C.-J.; Chan, T.-H. Organic
Reactions in Aqueous Media; Wiley: New York, 1997.
(b) Grieco, P. A. Organic Synthesis in Water; Kluwer
Academic Publishers: Dordrecht, 1997. (c) Herrmann, W.
A.; Kohlpaintner, C. W. Angew. Chem., Int. Ed. Engl. 1993,
32, 1524. (d) Lindström, U. M. Chem. Rev. 2002, 102, 2751.
(2) For reviews on heterogeneous-switching of organic
transformations, see: (a) Bailey, D. C.; Langer, S. H. Chem.
Rev. 1981, 81, 109. (b) Shuttleworth, S. J.; Allin, S. M.;
Sharma, P. K. Synthesis 1997, 1217. (c) Shuttleworth, S. J.;
Allin, S. M.; Wilson, R. D.; Nasturica, D. Synthesis 2000,
1035. (d) Dörwald, F. Z. Organic Synthesis on Solid Phase;
Wiley-VCH: Weinheim, 2000. (e) Leadbeater, N. E.;
Marco, M. Chem. Rev. 2002, 102, 3217. (f) Ley, S. V.;
Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.;
Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storer, R. I.;
Taylor, S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3815.
(g) McNamara, C. A.; Dixon, M. J.; Bradley, M. Chem. Rev.
2002, 102, 3275. (h) Chiral Catalyst Immobilization and
Recycling; De Vos, D. E.; Vankelecom, I. F. J.; Jacobs, P.
A., Eds.; Wiley-VCH: Weinheim, 2000. (i) Fan, Q.-H.; Li,
Y.-M.; Chan, A. S. C. Chem. Rev. 2002, 102, 3385.
(3) For recent reviews on solid-phase reactions using palladium
catalysts, see: (a) Uozumi, Y.; Hayashi, T. Solid-Phase
Palladium Catalysis for High-Throughput Organic
Synthesis, In Handbook of Combinatorial Chemistry;
Nicolaou, K. C.; Hanko, R.; Hartwig, W., Eds.; Wiley-VCH:
Weinheim, 2002, Chap. 19. (b) Uozumi, Y. Top. Curr.
Chem. 2004, 242, 77.
In summary, the asymmetric palladium-catalyzed p-allyl-
ic substitution of meso-cycloalkenyl-1,4-diacetates was
achieved with carbon, nitrogen, and oxygen nucleophiles
in water with an amphiphilic polymeric chiral palladium
complex to give the corresponding hemi-substituted prod-
ucts with high enantioselectivity of up to 99% ee. A de-
tailed kinetic study and synthetic application are currently
under investigation in our lab and will be reported in due
course.
Pd*
1
(5 mol% Pd)
AcO
OAc
+ PhOH
Cs2CO3 in H2O
meso-2
PhO
OAc
PhO
OPh
(4) For studies on polymer-supported catalysts from the
author’s group, see: (a) Cross-coupling: Uozumi, Y.;
Danjo, H.; Hayashi, T. J. Org. Chem. 1999, 64, 3384. (b)
Carbonylation reaction: Uozumi, Y.; Watanabe, T. J. Org.
Chem. 1999, 64, 6921. (c) Michael addition: Shibatomi, K.;
Nakahashi, T.; Uozumi, Y. Synlett 2000, 1643. Suzuki–
Miyaura coupling: (d) Uozumi, Y.; Nakai, Y. Org. Lett.
2002, 4, 2997. (e) Uozumi, Y.; Kikuchi, M. Synlett 2005,
1775. (f) Heck reaction: Uozumi, Y.; Kimura, T. Synlett
2002, 2045. (g) Rhodium catalysis: Uozumi, Y.; Nakazono,
M. Adv. Synth. Catal. 2002, 344, 274. (Wacker
6a
8
6a
8
yield; % ee
yield
conditions
2/PhOH = 1:1
2/PhOH = 5:1
25 °C
0 °C
55%; 98% ee
72%; 84% ee
12%
5%
2/PhOH = 1:1
2/PhOH = 5:1
64%; 99% ee
72%; 93% ee
14%
5%
cyclization): (h) Hocke, H.; Uozumi, Y. Synlett 2002,
2049. (i) Hocke, H.; Uozumi, Y. Tetrahedron 2003, 59,
619. (j) Sonogashira reaction: Uozumi, Y.; Kobayashi, Y.
Heterocycles 2003, 59, 71. Oxidation: (k) Uozumi, Y.;
Nakao, R. Angew. Chem. Int. Ed. 2003, 42, 194.
Scheme 4
Y
PhO
Y
PhO
(l) Uozumi, Y.; Nakao, R. Angew. Chem. 2003, 115, 204.
(m) Yamada, Y. M. A.; Arakawa, T.; Hocke, H.; Uozumi, Y.
Angew. Chem. Int. Ed. 2007, 46, 704. (n) Reduction:
Nakao, R.; Rhee, H.; Uozumi, Y. Org. Lett. 2005, 7, 163.
(o) Alkylation: Yamada, Y. M. A.; Uozumi, Y. Org. Lett.
2006, 8, 1375.
Pd*
Pd*
slow
6
fast
meso-2
8
(5) For studies on p-allylic transformations with polymer-
supported complex catalysts in water, see: (a) Uozumi, Y.;
Danjo, H.; Hayashi, T. Tetrahedron Lett. 1997, 38, 3557.
(b) Danjo, H.; Tanaka, D.; Hayashi, T.; Uozumi, Y.
Tetrahedron 1999, 55, 14341. (c) Uozumi, Y.; Suzuka, T.;
Kawade, R.; Takenaka, H. Synlett 2006, 2109.
slow
fast
Y
Y
OPh
ent-6
OPh
Pd*
Pd*
Scheme 5
Synlett 2008, No. 10, 1557–1561 © Thieme Stuttgart · New York

1560
Y. Uozumi et al.
CLUSTER
(6) For studies on heterogeneous aquacatalytic asymmetric p-
allylic transformations with polymer-supported complex
catalysts in water, see: (a) Alkylation: Uozumi, Y.; Danjo,
H.; Hayashi, T. Tetrahedron Lett. 1998, 39, 8303. (b)
Reduction with monodentate phosphine (MOP): Hocke, H.;
Uozumi, Y. Tetrahedron 2004, 60, 9297. (c) Alkylation:
Uozumi, Y.; Shibatomi, K. J. Am. Chem. Soc. 2001, 123,
2919. (d) Amination: Uozumi, Y.; Tanaka, H.; Shibatomi,
K. Org. Lett. 2004, 6, 281. (e) Cyclization: Nakai, Y.;
Uozumi, Y. Org. Lett. 2005, 7, 291. (f) Etherification:
Uozumi, Y.; Kimura, M. Tetrahedron: Asymmetry 2006, 17,
161. (g) Nitromethylation: Uozumi, Y.; Suzuka, T. J. Org.
Chem. 2006, 71, 8644. (h) Kobayashi, Y.; Tanaka, D.;
Danjo, H.; Uozumi, Y. Adv. Synth. Catal. 2006, 348, 1561.
(i) Uozumi, Y. Pure Appl. Chem. 2007, 79, 1481.
(7) For recent reviews on asymmetric p-allylic substitution,
see: (a) Acemoglu, L.; Williams, J. M. J. Handbook of
Organopalladium Chemistry for Organic Synthesis;
Negishi, E.; de Meijere, A., Eds.; Wiley: New York, 2002.
(b) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103,
2921.
(dt, J = 7.3, 14.6 Hz, 1 H), 2.05 (s, 3 H), 1.89 (dt, J = 4.0,
14.6 Hz, 1 H). 13C NMR (CDCl3): d = 170.77, 157.77,
135.05, 134.06, 129.53, 115.34, 79.55, 76.74, 37.94, 21.08.
IR (ATR): 1733, 1493, 1366, 1228, 1087, 889, 754, 692, 628
cm–1. MS (EI): m/z (%rel intensity) = 218 (0.7) [M+], 43
(base peak). Anal. Calcd for C13H14O3: C, 71.54; H, 6.47.
Found: C, 71.49; H, 6.53. CAS registry number: 210701-
09-0.
1-Acetoxy-4-(2-benzyloxyphenoxy)-2-cyclopentene (6b):
[a]D28 –20.5 (c = 1.0, CHCl3); 97% ee. 1H NMR (CDCl3):
d = 7.43–7.27 (m, 4 H), 6.89–6.98 (m, 5 H), 6.26 (br d, J =
4.8 Hz, 1 H), 6.09 (br d, J = 4.8 Hz, 1 H), 5.57 (br, 1 H), 5.17
(br, 1 H), 5.12 (s, 2 H), 2.93 (dt, J = 7.3, 14.6 Hz, 1 H), 2.04
(s, 3 H), 1.98 (dt, J = 4.3, 14.6 Hz, 1 H). 13C NMR (CDCl3):
d = 170.88, 149.49, 148.28, 137.32, 134.67, 133.73, 128.45,
127.78, 127.29, 122.21, 121.70, 117.09, 115.60, 81.72,
76.79, 71.31, 38.08, 21.13. IR (ATR): 1732, 1499, 1452,
1366, 1236, 1212, 1083, 1012, 896, 742, 697, 627 cm–1. MS
(EI): m/z (%rel intensity) = 324 (1) [M+], 91 (base peak).
Anal Calcd for C20H20O4: C, 74.06; H, 6.21. Found: C,
73.94; H, 6.28.
26
(8) (a) Taniimori, S.; Tsuji, Y.; Kirihara, M. Biosci.,
Biotechnol., Biochem. 2002, 66, 660. (b) Song, E. S.; Yang,
J. W.; Roh, E. J.; Lee, S.-G.; Han, H. Angew. Chem. Int. Ed.
2002, 41, 3852. (c) Trost, B. M.; Van Vranken, D. L.;
Bingel, C. J. Am. Chem. Soc. 1992, 114, 9327.
1-Acetoxy-4-(2-chlorophenoxy)-2-cyclopentene(6c):[a]D
–58.0 (c = 1.0, CHCl3). 1H NMR (CDCl3): d = 7.37 (dd, J =
1.8, 7.9 Hz, 1 H), 7.20 (dt, J = 1.8, 7.9 Hz, 1 H), 6.95 (d, J =
7.9 Hz, 1 H), 6.92 (t, J = 7.9 Hz, 1 H), 6.26 (d, J = 5.5 Hz, 1
H), 6.14 (J = 5.5 Hz, 1 H), 5.60 (br, 1 H), 5.17 (br, 1 H), 2.99
(dt, J = 7.3, 14.6 Hz, 1 H), 2.06 (s, 3 H), 1.96 (dt, J = 4.3,
14.6 Hz, 1 H). 13C NMR (CDCl3): d = 170.84, 153.65,
134.65, 134.46, 130.57, 127.66, 123.71, 121.94, 115.26,
81.33, 76.61, 38.02, 21.11. IR (ATR): 1237, 1090, 902, 730,
649, 630 cm–1. MS (EI): m/z (%rel intensity): = 252 (0.02)
[M+], 43 (base peak).
(9) Trost B. M., Pulley S. R., Bingel C.; Tetrahedron Lett.;
1995, 36: 8737.
(10) Tenta Gel SNH2 (purchased from Rapp Polymere) was used
as the polymer support.
(11) Chemical yield of the monosubstituted product 4 was
lowered to <30% with Li2CO3, NaHCO3, Na2CO3, or
K2CO3.
(12) The absolute configuration of 4 was determined by chemical
correlation with (1R,4S)-cis-1-acetoxy-4-[bis(methoxy-
carbonyl)methyl]-2-cyclopentene (see ref. 8a).
(13) Nishiyama, H.; Sakata, N.; Sugimoto, H.; Motoyama, Y.;
Wakita, H.; Nagase, H. Synlett 1998, 930.
(14) The absolute configuration of 6a was determined to be 1R,4S
by measurement of the specific rotation (see, ref. 12). The
configurations of 6b–g were tentatively assigned on the
basis of the mechanistic similarity of the asymmetric
induction, as depicted in Table 1.
(15) Palladium-Catalyzed Asymmetric Desymmetrization of
meso-Cycloalkene-1,4-diacetate: Reaction conditions and
results are shown in Table 1. A typical procedure is given for
the reaction with cis-1,4-diacetoxycyclopentene (meso-2)
and phenol (a) in H2O (entry 3).
1-Acetoxy-4-(2-bromophenoxy)-2-cyclopentene (6d):
[a]D25 –100.8 (c = 1.1, CHCl3); 95% ee. 1H NMR (CDCl3):
d = 7.55 (dd, J = 1.2, 7.9 Hz, 1 H), 7.25 (td, J = 1.2, 7.3 Hz,
1 H), 6.94 (d, J = 1.2 Hz, 1 H), 6.85 (td, J = 1.2, 7.9 Hz, 1 H),
6.26 (d, J = 5.5 Hz, 1 H), 6.14 (d, J = 5.5 Hz, 1 H), 5.60 (br
t, J = 5.5 Hz, 1 H), 5.17 (br t, J = 5.5 Hz, 1 H), 2.07 (s, 3 H),
2.00 (dt, J = 7.3, 14.6 Hz, 1 H), 1.96 (dt, J = 4.2, 14.6 Hz, 1
H). 13C NMR (CDCl3): d = 170.79, 154.52, 134.60, 134.39,
133.61, 128.37, 122.34, 114.99, 113.00, 81.34, 76.55, 38.00,
21.07. IR (ATR): 1733, 1584, 1573, 1474, 1442, 1366, 1085,
1029, 895, 748, 627 cm–1. MS (EI): m/z (%rel intensity) =
296 (0.02) [M+], 43 (base peak). Anal. Calcd for
C13H13BrO3: C, 52.55; H, 4.41. Found: C, 52.37; H, 4.37.
1-Acetoxy-4-(2,6-dimethylphenoxy)-2-cyclopentene (6e):
[a]D27 –41.4 (c = 1.1, CHCl3). 1H NMR (CDCl3): d = 7.02 (d,
J = 7.3 Hz, 2 H), 6.92 (t, J = 7.3 Hz, 1 H), 6.16 (d, J = 5.4
Hz, 1 H), 6.05 (d, J = 5.4 Hz, 1 H), 5.52 (br t, J = 4.4 Hz, 1
H), 4.81 (br t, J = 6.3 Hz, 1 H), 2.88 (dt, J = 7.3, 14.6 Hz, 1
H), 2.30 (s, 6 H), 2.09 (s, 3 H), 2.06 (dt, J = 4.4, 14.6 Hz, 1
H). 13C NMR (CDCl3): d = 171.09, 155.79, 136.60, 133.37,
131.06, 129.16, 123.95, 84.66, 76.73, 38.51, 21.39, 17.46.
IR (ATR): 1730, 1365, 1237, 1198, 1091, 903, 730, 649, 630
cm–1. MS (EI): m/z (%rel intensity) = 246 (0.09) [M+], 43
(base peak). HRMS (EI): m/z [M+] calcd for C15H18O3:
246.1256; found: 246.1251. The enantiomeric excess was
determined by HPLC analysis using a chiral stationary phase
column [Chiralcel OD-H, eluent: n-hexane–2-propanol,
50:1; flow rate: 0.5 mL/min; tR (major isomer) = 14.73 min
and tR (minor isomer) = 13.98 min] to be 90% ee.
To a mixture of the catalyst 1 (89 mg, 0.025 mmol) and
meso-2 (92 mg, 0.5 mmol) in H2O (2.5 mL) was added
phenol (48 mg, 0.5 mmol), and the mixture was shaken at
0 °C for 18 h. The reaction mixture was filtered and the
recovered resin beads were rinsed with EtOAc (3 ×). The
combined filtrate was dried over anhyd Na2SO4. The solvent
was evaporated and the residue was chromatographed on
silica gel (hexane–EtOAc, 10:1) to give 1-acetoxy-4-
phenoxycyclopentene (6a; 70 mg, 64% yield) and 1,4-
diphenoxycyclopentene (8; 18 mg). The enantiomeric
excess was determined to be 99% ee by GC analysis using a
chiral stationary phase capillary column (Cyclodex CB).
Spectral and analytical data for compounds 6 are shown
below, where the enantiomeric excesses were determined by
GC (Cyclodex CB), unless otherwise noted: 1-Acetoxy-4-
phenoxycyclopentene (6a): [a]D23 +63.8 (c = 1.0, CHCl3). 1H
NMR (CDCl3): d = 7.29 (t, J = 7.8 Hz, 2 H), 6.96 (t, J = 7.3
Hz, 1 H), 6.92 (d, J = 7.8 Hz, 2 H), 6.24 (d, J = 5.8 Hz, 1 H),
6.12 (d, J = 5.3 Hz, 1 H), 5.61 (br, 1 H), 5.17 (br, 1 H), 2.97
1-Acetoxy-4-(3-methoxyphenoxy)-2-cyclopentene (6f):
[a]D26 +57.5 (c = 1.1, CHCl3); 96% ee. 1H NMR (CDCl3):
d = 7.18 (t, J = 8.5 Hz, 1 H), 6.52 [td, J = 2.4, 8.5 Hz
(overlapped), 2 H], 6.48 (t, J = 2.4 Hz, 1 H), 6.24 (d, J = 5.5
Hz, 1 H), 6.13 (d, J = 5.5 Hz, 1 H), 5.60 (br, 1 H), 5.16 (br,
1 H), 3.78 (s, 3 H), 2.96 (dt, J = 7.3, 14.6 Hz, 1 H), 2.05 (s,
Synlett 2008, No. 10, 1557–1561 © Thieme Stuttgart · New York

CLUSTER
3 H), 1.88 (dt, J = 3.9, 14.6 Hz, 1 H). 13C NMR (CDCl3):
Allylic Substitution of meso-1,4-Diacetoxycycloalkenes
1561
732, 630 cm–1. MS (EI): m/z (%rel intensity) = 274 (0.2)
[M+], 43 (base peak). Anal. Calcd for C17H22O3: C, 74.42; H,
8.08. Found: C, 74.56; H, 8.22.
d = 170.77, 160.87, 158.99, 134.98, 134.12, 129.95, 107.35,
106.54, 101.88, 79.62, 55.24, 37.90, 21.04. IR (ATR): 1733,
1602, 1491, 1366, 1235, 1199, 1150, 1087, 1015, 891, 837,
765, 687, 629 cm–1. MS (EI): m/z (%rel intensity) = 248 (1)
[M+], 43 (base peak). Anal. Calcd for C14H16O4: C, 67.73; H,
6.50. Found: C, 67.51; H, 6.45.
1-Acetoxy-4-(4-tert-buthylphenoxy)-2-cyclopentene (6g):
[a]D27 +148.7 (c = 1.4, CHCl3); 94% ee. 1H NMR (CDCl3):
d = 7.30 (d, J = 8.5 Hz, 2 H), 6.85 (d, J = 8.5 Hz, 2 H), 6.24
(d, J = 5.5 Hz, 1 H), 6.11 (d, J = 5.5 Hz, 1 H), 5.60 (s, 1 H),
5.14 (s, 1 H), 2.96 (dt, J = 7.3, 14.6 Hz, 1 H), 2.05 (s, 3 H),
1.89 (dt, J = 3.9, 14.6 Hz, 1 H), 1.37 (s, 9 H). 13C NMR
(CDCl3): d = 170.79, 155.51, 143.66, 135.25, 133.90,
126.30, 114.78, 79.61, 76.79, 37.98, 34.05, 31.48, 21.08. IR
(ATR): 1736, 1511, 1365, 1232, 1185, 1087, 1013, 898, 829,
1-Acetoxy-4-phenoxy-2-cyclohexene (7): 1H NMR
(CDCl3): d = 7.26–7.31 (m, 2 H), 6.92–6.97 (m, 3 H), 6.08
(ddd, J = 1.2, 3.7, 10.0 Hz, 1 H), 6.07 (ddd, J = 1.2, 3.0, 10.0
Hz, 1 H), 5.25 (br s, 1 H), 4.76 (br s, 1 H), 2.07 (s, 3 H), 1.87–
2.02 (m, 4 H). 13C NMR (CDCl3): d = 170.72, 157.52,
131.10, 129.59, 121.06, 115.84, 70.27, 67.38, 24.92, 24.75,
21.27. IR (ATR): 1730, 1597, 1492, 1371, 1226, 1079, 1035,
958, 903, 754, 692 cm–1. MS (EI): m/z = 232 [M+]. The
enantiomeric excess was determined by HPLC analysis
using a chiral stationary phase column [Chiralcel OD-H,
eluent: n-hexane–2-propanol, 50:1; flow rate: 0.5 mL/min; tR
(major isomer) = 21.33 min and tR (minor isomer) = 18.48
min] to be 95% ee.
Synlett 2008, No. 10, 1557–1561 © Thieme Stuttgart · New York