Highly enantioselective copper-catalyzed conjugate addition of diethylzinc to enones using chiral spiro phosphoramidites as ligands

Article abstract of DOI:10.1021/jo026611m

Novel monodentate chiral spiro phosphoramidite ligands have been readily synthesized in good yields from enantiomerically pure 1,1′-spirobiindane-7,7′-diol. The new ligands were highly efficient in the copper-catalyzed conjugate addition of Et₂

Full text of DOI:10.1021/jo026611m

High ly En a n tioselective Cop p er -Ca ta lyzed
Con ju ga te Ad d ition of Dieth ylzin c to
En on es Usin g Ch ir a l Sp ir o
P h osp h or a m id ites a s Liga n d s
Hai Zhou, Wen-Hu Wang, Yu Fu, J ian-Hua Xie,
Wen-J ian Shi, Li-Xin Wang, and Qi-Lin Zhou*
State Key Laboratory and Institute of Elemento-organic
Chemistry, Nankai University, Tianjin 300071, P. R. China
F IGURE 1. Siphos ligands used in Cu-catalyzed conjugate
addition of Et2Zn to enones.
qlzhou@public.tpt.tj.cn
Received October 25, 2002
SCHEME 1
Abstr a ct: Novel monodentate chiral spiro phosphoramidite
ligands have been readily synthesized in good yields from
enantiomerically pure 1,1′-spirobiindane-7,7′-diol. The new
ligands were highly efficient in the copper-catalyzed conju-
gate addition of Et2Zn to enones with up to 98% enantio-
meric excess.
The conjugate addition of organometallic reagents to
R,â-unsaturated carbonyl compounds is one of the most
useful processes for C-C bond formation in organic
synthesis.1 A number of chiral auxiliaries and stoichio-
metric reagents have been reported during the past
decade that have provided high enantioselectivity in the
1,4-addition,2 while the chiral catalyst has been developed
with less success. Recently, the copper complexes with
chiral phosphorus ligands have been found to be highly
efficient catalysts in the conjugate addition of Et2Zn to
enones.3 Among those chiral ligands, BINOL-based phos-
phoramidites developed by Feringa et al.4 and TADDOL-
derived phosphites reported by Alexakis et al.5 showed
a remarkable enantioselectivity in the reaction of Et2Zn
with cyclohexenones. Other efficient chiral ligands in-
clude diphosphite6 and P,N ligands.7 However, the ligands
that have been demonstrated to induce high enantiose-
lectivities are only limited to those with BINOL or
TADDOL as a chiral backbone.
olefins.8 It is of interest to study the behavior of these
novel monodentate ligands in other types of transition
metal-catalyzed transformations. Herein we describe the
copper-catalyzed conjugate addition of Et2Zn to enones
using spiro phosphoramidite ligands 1 and 2 with high
enantioselectivity. Chiral spiro phosphoramidite ligands
1 and 2 were conveniently synthesized in good yields from
enantiomerically pure 1,1′-spirobiindane-7,7′-diol (3),
which could be easily prepared from 3-methoxybenzal-
dehyde9 (Scheme 1). Heating the mixture of diol 3 and
P(NMe2)3 or P(NEt2)3 in toluene for 2 h afforded ligands
1a or 1b in 86-92% yield, while ligands 1c, 1d , and 2,
which bear a bulk amino group, were produced with a
different procedure. Condensation of diol 3 with PCl3,
followed by treatment with the corresponding lithium
dialkylamide provided ligands 1c, 1d , and 2 in 50-66%
yield.
2-Cyclohexen-1-one was chosen as a typical substrate
to test chiral ligands. The conjugate addition of Et2Zn to
cyclohexenone was carried out in the presence of Cu(OTf)2
(1 mol %) and chiral ligands (2 mol %) in toluene at 0 °C
for 2 h producing 3-ethylcyclohexanone in high yields.
The results summarized in Table 1 showed that the
structure of the ligand has a strong influence on the
enantioselectivity of the reaction. Ligands 1a and 1b, in
which R groups are methyl and ethyl, respectively, gave
(S)-product 5 in low ee. Introduction of a larger R group
in ligands 1, such as isopropyl in 1c and cyclohexyl in
1d , led to higher enantioselectivities. A significant im-
provement in the enantioselectivity (97% ee) was achieved
by using ligand (R,R,R)-2, which contains a C2-symmetric
We have previously reported the phosphoramidites of
general structure 1 (Siphos), which contain a chiral
spirobiindane structure to be efficient ligands in the
asymmetric Rh-catalyzed hydrogenation of prochiral
(1) For reviews, see (a) Tomioka, K.; Nagaoka, Y. In Comprehensive
Asymmteric Catalysis; Springer: New York, 1999; Vol. 1, Chapter 31,
p 1105. (b) Krause, N.; Hoffmann-Ro¨der, A. Synthesis 2001, 2, 171.
(2) (a) Rossiter, B. E.; Swingle, H. M. Chem. Rev. 1992, 92, 771. (b)
Advanced Asymmetric Synthesis; Stephenson, G. R., Ed.; Chapman and
Hall: London, 1996.
(3) Alexakis, A.; Benhaim, C. Eur. J . Org. Chem. 2002, 3221.
(4) (a) de Vries, A. H. M.; Meetsma, A.; Feringa, B. L. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 2374. (b) Feringa, B. L.; Pineschi, M.; Arnold,
A.; Imbos, R.; de Vries, A. H. M. Angew. Chem., Int. Ed. Engl. 1997,
36, 2620. (c) Imbos, R.; Brilman, M. H. G.; Rineschi, M.; Feringa, B.
L. Org. Lett. 1999, 1, 623. (d) Choi, Y. H.; Choi, J . Y.; Yang, H. Y.;
Kim, Y. H. Tetrahedron: Asymmetry 2002, 13, 801.
(5) Alexakis, A.; Vastra, J .; Burton, J .; Benhaim, C.; Mangeney, P.
Tetrahedron Lett. 1998, 39, 7869.
(6) (a) Yang, M.; Chan, A. S. C. Tetrahedron Lett. 1999, 40, 6645.
(b) Yan, M.; Zhou, Z.-Y.; Chan, A. S. C. Chem. Commun. 2000, 115. (c)
Reetz, M. T.; Gosberg, A.; Moulin, D. Tetrahedron Lett. 2002, 43, 1189.
(7) (a) Hu, X.; Chen, H.; Zhang, X. Angew. Chem., Int. Ed. 1999,
38, 3518. (b) Escher, I. H.; Pfaltz, A. Tetrahedron 2000, 56, 2879.
(8) (a) Fu, Y.; Xie, J .-H.; Hu, A.-G.; Zhou, H.; Wang, L.-X.; Zhou,
Q.-L. Chem. Commun. 2002, 480. (b) Hu, A.-G.; Fu, Y.; Xie, J .-H.; Zhou,
H.; Wang, L.-X.; Zhou, Q.-L. Angew. Chem., Int. Ed. 2002, 41, 2348.
(9) (a) Birman, V. B.; Rheingold, A. L.; Lam, K.-C. Tetrahedron:
Asymmetry 1999, 10, 125. (b) Zhang, J .-H.; Liao, J .; Cui, X.; Yu, K.-B.;
Deng, J .-G.; Zhu, S.-F.; Wang, L.-X.; Zhou, Q.-L.; Chung L.-W.; Ye, T.
Tetrahedron: Asymmtry 2002, 13, 1363.
10.1021/jo026611m CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/11/2003
1582
J . Org. Chem. 2003, 68, 1582-1584

TABLE 1. Asym m etr ic Con ju ga te Ad d ition of Et 2Zn to
TABLE 3. Asym m etr ic Con ju ga te Ad d ition of Et 2Zn to
Acyclic En on es 6a
Cycloh exen on e Ca ta lyzed by Cu (OTf)2-L Com p lexesa
yield
(%)b
ee
yield
(%)b
ee
entry
ligand
(%)c
configurationd
entry
R1
ligand
1a
1b
1c
1d
(R,R,R)-2
(S,R,R)-2
1c
1d
1c
1d
(%) c
1
2
3
4
5
6
1a
94
88
87
90
95
93
34
35
57
70
97
74
S
S
S
S
S
R
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
68
87
89
87
65
70
80
74
87
77
37 (R)
52 (R)
71 (R)
64 (R)
70 (R)
30 (S)
44 (nd)
40 (nd)
76 (nd)
72 (nd)
1b
1c
1d
(R,R,R)-2
(S,R,R)-2
a
4-CH3OPh
4-CH3OPh
4-ClPh
Reaction conditions: 2-cyclohexen-1-one (1 mmol), Et2Zn (1.5
mmol), Cu(OTf)2 (0.01 mmol), ligands 1 or 2 (0.02 mmol) in toluene
(3 mL). Isolated yields. c Ee values were determined by chiral
b
d
10
4-ClPh
GC on a Supelco γ-DEX-225 column. Absolute configuration was
determined by comparison with literature values.10
a
Reaction conditions: enone (1 mmol), Et2Zn (1.5 mmol),
Cu(OTf)2 (0.03 mmol), ligand (0.06 mmol). Isolated yields. c De-
b
termined by HPLC (Chiracel OJ column, 99:1 n-hexane/2-propanol,
1 mL/min). Absolute configurations were determined by compari-
son with literature values.12
TABLE 2. Asym m etr ic Con ju ga te Ad d ition of Et 2Zn to
Cycloh exen on e w ith Liga n d (R,R,R)-2a
temp
(°C)
yield
(%)b
ee
(%)
entry
Cu salt
Cu(OTf)2
solvent
(R,R,R)-2, the reaction of cycloheptenone produced 1,4-
addition product 3-ethylcycloheptanone with 94% ee.
However, the reaction of cyclopentenone provided 3-eth-
ylcyclopentanone with only 44% ee.
1
2
toluene
Et2O
CH2Cl2
THF
EtOAc
toluene
toluene
toluene
toluene
toluene
toluene
toluene
0
0
95
93
95
85
91
96
92
99
88
91
92
74
97
95
86
75
93
95
91
96
98
96
95
90
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OAc)2‚2H2O
CuCl2‚2H2O
CuCl
3
0
4
0
5
0
To extend the range of substrates for these catalysts,
the conjugate addition of Et2Zn to acyclic enones has been
studied (Table 3). In the case of chalcone, the ligands with
larger R groups afforded conjugate addition product 7
with higher ee (entries 1-4). Ligand (R,R,R)-2, with a
matched combination of chiralities of spiro skeleton and
amino moiety, however, did not show its superiority in
the enantioselectivity over ligand 1c like that in the
reaction of cyclohexenone (entry 5 vs 3). The substitution
of the electron-withdrawing chlorine atom on the phenyl
ring of chalcone did not have much influence on the
enantioselectivity of the reaction, while the introduction
of an electron-donating methoxy group led to lower ee
values.
6
-20
-40
25
0
7
8
9
10
11
12
0
0
CuBr
0
a
b
All reactions were completed in 2 h. Isolated yields; no 1,2-
addition products were observed.
(R,R)-di(1-phenylethyl)amine moiety, while with ligand
(S,R,R)-2 prepared from (S)-3 and (R,R)-di(1-phenylethy-
l)amine, a mismatched case, (R)-product 5, was produced
with only 74% ee. By comparing the absolute configura-
tion of products from ligands (R,R,R)-2 and (S,R,R)-2
(entries 5 and 6), we can see that the configuration of
the product was determined by the chirality of the spiro
backbone of the ligand.
Having realized the efficient stereocontrol of ligand
(R,R,R)-2 in the Cu-catalyzed conjugate addition of Et2-
Zn to cyclohexenone, we investigated the effects of
solvent, temperature, and the catalyst precursor to
optimize the reaction conditions (Table 2). Of the solvents
screened, nonpolar solvents such as toluene and Et2O
were superior to coordinating solvents such as THF
(entries 1-5). By lowering the reaction temperature from
0 to -40 °C, the ee of product 5 decreased from 97 to
91% (entries 6 and 7 vs 1). It is noteworthy that the
conjugate addition reaction can be carried out at room
temperature with high enantioselectivity (entry 8), which
offers an advantage of ligand (R,R,R)-2 over other mono-
dentate phosphorus ligands that normally need a low
temperature.4,11 In addition to Cu(OTf)2, other copper
salts like Cu(OAc)2‚2H2O, CuCl2‚2H2O, and CuCl were
also found to be effective catalyst precursors in the
conjugate addition of Et2Zn to cyclohexenone (entries
9-12).11
In summary, we have demonstrated that monodentate
chiral phosphoramidites with a spiro structure are highly
efficient ligands in the copper-catalyzed 1,4-addition of
Et2Zn to cyclic enones. The reaction can be carried out
under mild conditions. Further studies of other transition
metal-catalyzed reactions using our novel ligands are in
progress.
Exp er im en ta l Section
Gen er a l. All reactions and manipulations were performed in
an argon atmosphere using standard Schlenk techniques. Tolu-
ene, ether, and THF were distilled from sodium-benzophenone
ketyl under argon. Methylene chloride and ethyl acetate were
distilled from CaH2. 1,1′-Spirobiindane-7,7′-diol was prepared
and resolved by previously reported methods.9
The conjugate additions of Et2Zn to cycloheptenone and
cyclopentenone were also examined. By using ligand
(10) Posner, G. H.; Frye, L. L. Isr. J . Chem. 1984, 24, 88.
(11) Alexakis, A.; Benhaim, C.; Rosset, S.; Humam, M. J . Am. Chem.
Soc. 2002, 124, 5262.
Syn th eses of Liga n d s: Syn th esis of N-Dim eth yl-[(R)-1,1′-
spir obiin dan e-7,7′-diyl]ph osph or am idite (1a). Typical P r o-
(12) Kno¨bel, A. K. H.; Escher, I. J .; Pfaltz, A. Synlett 1997, 1429.
J . Org. Chem, Vol. 68, No. 4, 2003 1583

ced u r e. A mixture of (R)-1,1′-spirobiindane-7,7′-diol (200 mg,
0.8 mmol), HMPT (0.2 mL, 1 mmol), and 2 mL of dry toluene
was heated at reflux under argon for 2 h. After cooling to room
temperature, the mixture was concentrated and purified by
chromatography on a silica gel column with 16:1 petroleum
ether/EtOAc to give 1a as a white solid (237 mg, 92% yield).
Mp: 84-85 °C; [R]D25 +519 (c 0.092, CHCl3). 1H NMR (300 MHz,
CDCl3): δ 7.22-6.63 (m, 6H), 3.13-3.01 (m, 2H), 2.86-2.78 (m,
2H), 2.34 (s, 3H), 2.31 (s, 3H), 2.29-2.19 (m, 2H), 2.07-1.89 (m,
2H). 13C NMR (75 MHz, CDCl3): δ 148.3, 146.2, 146.0, 145.7,
145.2, 142.1, 140.8, 128.3, 128.2, 121.5, 121.1, 120.0, 58.7, 38.2,
38.1, 35.4, 35.0, 30.8, 30.5. 31P NMR (121 MHz, CDCl3): δ 124.9.
MS: m/z 325 (M+, 100). Anal. Calcd for C19H20NO2P: C, 70.13;
H, 6.21; N, 4.30. Found: C, 69.95; H, 6.06; N, 4.40.
1-phenylethyl]amine. White solid, mp 82-84 °C, [R]25 +1050
D
(c 0.096, CHCl3). 1H NMR (300 MHz, CDCl3): δ 7.38-6.63 (m,
15H), 6.69 (d, J ) 7.8 Hz, 1H), 4.50-4.21 (m, 2H), 3.20-2.95
(m, 2H), 2.92-2.70 (m, 2H), 2.40-1.81 (m, 4H), 1.78-1.35 (m,
6H). 13C NMR (75 MHz, CDCl3): δ 147.6, 146.9, 145.7, 145.0,
143.6, 140.1, 128.4, 127.8, 127.6, 126.4, 122.0, 121.2, 121.0, 120.6,
58.9, 52.3, 52.1, 38.4, 38.1, 30.7, 30.4, 21.9. 31P NMR (121 MHz,
CDCl3): δ 130.2. HR-MS (FAB) calcd for C33H32NO2P + H
506.2243; found 506.2234.
N-Di[(R)-1-p h en yleth yl]-[(S)-1,1′-sp ir obiin d a n e-7,7′-diyl]-
p h osp h or a m id ite (S,R,R)-2. Ligand (S,R,R)-2 was synthesized
in 66% yield from (S)-3 and di[(R)-1-phenylethyl]amine by using
the same procedure as that for 1c. White solid, mp 50-52 °C;
[R]25D -31 (c 0.92, CHCl3). 1H NMR (300 MHz, CDCl3): δ 7.26-
6.75 (m, 15H), 5.97 (d, J ) 7.8 Hz, 1H), 4.40-4.28 (m, 2H), 3.14-
2.92 (m, 2H), 2.85-2.72 (m, 2H), 2.30-2.10 (m, 2H), 2.05-1.81
(m, 2H), 1.60 (d, J ) 6.9 Hz, 6H). 13C NMR (75 MHz, CDCl3): δ
148.1, 145.0, 144.7, 143.6, 142.5, 140.6, 139.0, 127.9, 127.5, 127.0,
126.9, 126.6, 125.6, 120.8, 120.1, 119.3, 59.1, 57.8, 54.2, 37.2,
36.9, 29.6, 29.2, 21.8, 21.6. 31P NMR (121 MHz, CDCl3): δ 137.2.
HR-MS (FAB) calcd for C33H32NO2P + H 506.2243; found
506.2238.
Gen er a l P r oced u r e for Asym m etr ic Ca ta lytic Con ju ga te
Ad d ition . A solution of copper salt (0.01 mmol) and ligand (0.02
mmol) in an appropriate solvent (3 mL) was stirred under argon
at room temperature for 30 min. The solution was cooled to 0
°C, and Et2Zn solution in hexane (1.5 mmol) and the enone (1
mmol) were added. After 2 h at 0 °C, the reaction was quenched
by aqueous NH4Cl and the mixture was extracted with Et2O (2
× 20 mL). The organic phases were combined, dried (Na2SO4),
filtered, and concentrated. The crude product was purified by
chromatography on a silica gel column. The ee values of cyclic
ketones were determined by chiral GC, and the ee values of
acyclic ketone were determined by chiral HPLC. The analytic
conditions are as follows.
N-Diet h yl-[(R)-1,1′-sp ir ob iin d a n e-7,7′-d iyl]p h osp h or -
a m id ite (1b). Ligand 1b was synthesized in 86% yield by the
same procedure as that for 1a using hexaethylphosphorus
triamide. Compound 1b is a colorless oil and solidifies slowly
25
by standing. [R]D +393 (c 0.098, CHCl3). 1H NMR (300 MHz,
CDCl3): δ 7.26-6.62 (m, 6H), 3.14-2.98 (m, 2H), 2.86-2.52 (m,
6H), 2.52-2.18 (m, 2H), 2.06-1.88 (m, 2H), 1.01 (t, J ) 7.1 Hz,
6H). 13C NMR (75 MHz, CDCl3): δ 147.9, 146.5, 146.1, 145.6,
145.3, 141.6, 141.0, 128.5, 128.1, 121.8, 120.9, 120.4, 59.0, 39.2,
38.4, 31.0, 15.3. 31P NMR (121 MHz, CDCl3): δ 129.1. MS: m/z
353 (M+), 338 (100). Anal. Calcd for C21H24NO2P: C, 71.35; H,
6.86; N, 3.96. Found: C, 71.06; H, 6.65; N, 3.82.
Syn th esis of N-Diisop r op yl-[(R)-1,1′-sp ir obiin d a n e-7,7′-
d iyl]p h osp h or a m id ite (1c). Typ ica l P r oced u r e. A solution
of (R)-1,1′-spirobiindane-7,7′-diol (200 mg, 0.8 mmol) in 10 mL
toluene was added over a period of 5 min to a cooled solution
(-78 °C) of PCl3 (69.4 µL, 0.8 mmol), Et3N (223 µL, 1.6 mmol),
and toluene (5 mL). The reaction mixture was stirred for 2 h,
warmed to room temperature, and filtered. The filtrate was
cooled to -78 °C and treated with a 0.16 M solution of LDA (5
mL, 0.8 mmol, newly prepared) for 3 h. The reaction mixture
was warmed to room temperature, stirred overnight, filtered,
concentrated, and purified by chromatography on a silica gel
column with 30:1 petroleum ether/EtOAc to give 1c as a white
3-Eth yl-cycloh exa n on e: Supelco γ-DEX-225 column (30 m
× 0.25 mm i.d.) at 95 °C constant, TR ) 27.91 and 28.54 min.
3-Eth yl-cyclop en ta n on e: Supelco γ-DEX-225 column (30 m
× 0.25 mm i.d.) at 90 °C constant, TR ) 19.23 and 19.65 min.
25
solid (168 mg, 55% yield). Mp: 90-92 °C; [R]D +376 (c 0.1,
CHCl3). 1H NMR (300 MHz, CDCl3): δ 7.22-6.84 (m, 6H), 3.12-
3.00 (m, 4H), 2.87-2.75 (m, 2H), 2.28-2.16 (m, 2H), 2.06-1.85
(m, 2H), 1.17 (d, J ) 6.3 Hz, 6H), 1.10 (d, J ) 6.3 Hz, 6H). 13C
NMR (75 MHz, CDCl3): δ 148.9, 147.2, 146.5, 145.7, 144.1, 141.5,
139.74, 128.0, 127.0, 121.8, 121.3, 120.6, 119.5, 57.6, 37.0, 29.6,
23.3. 31P NMR (121 MHz, CDCl3): δ 135.5. MS: m/z 381 (M+),
281 (100). Anal. Calcd for C23H28NO2P: C, 72.49; H, 7.42; N,
3.67. Found: C, 72.24; H, 7.18; N, 3.53.
3-Eth yl-cycloh ep ta n on e: Supelco â-DEX-120 column (30 m
× 0.25 mm i.d.), at 95 °C for 5 min, then programmed to increase
at 1 °C/min to 150 °C, TR ) 31.88 and 32.27 min.
1,3-Dip h en yl-p en ta n -1-on e: Chiracel OJ column (25 cm ×
0.46 cm i.d.), 99:1 n-hexane/2-propanol, 1 mL/min, TR ) 28.91
and 33.54 min.
1-P h en yl-3-(4-m eth xoyp h en yl)p en ta n -1-on e: Chiracel OJ
column (25 cm × 0.46 cm i.d.), 99:1 n-hexane/2-propanol, 1 mL/
min, TR ) 30.43 and 37.87 min.
1-P h en yl-3-(4-ch lor op h en yl)p en ta n -1-on e: Chiracel OJ
column (25 cm × 0.46 cm ID), n-hexane, 1 mL/min, TR ) 41.67
and 50.99 min.
N-Dicycloh exyl-[(R)-1,1′-sp ir ob iin d a n e-7,7′-d iyl]p h os-
p h or a m id ite (1d ). Ligand 1d was synthesized in 56% yield by
the same procedure as that for 1c using dicyclohexylamine.
White solid, mp 190-192 °C, [R]25D +272 (c 0.5, CHCl3). 1H NMR
(300 MHz, CDCl3): δ 7.27-6.70 (m, 6H), 3.14-2.98 (m, 2H),
2.89-2.74 (m, 2H), 2.62-2.38 (m, 2H), 2.29-2.13 (m, 2H), 2.09-
1.83 (m, 2H), 1.82-1.20 (m, 14H), 1.18-0.72 (m, 6H). 13C NMR
(75 MHz, CDCl3): δ 149.6, 146.8, 145.6, 144.6, 141.7, 140.1,
128.3, 127.9, 121.9, 121.3, 120.7, 120.1, 58.8, 54.6, 54.4, 38.2,
38.0, 35.6, 35.4, 30.8, 30.4, 26.7, 25.6. 31P NMR (121 MHz,
CDCl3): δ 135.0. Anal. Calcd for C29H36NO2P: C, 75.46; H, 7.86;
N, 3.03. Found: C, 75.11; H, 7.84; N, 3.03.
Ack n ow led gm en t . Financial support from the
National Natural Science Foundation of China, the
Major Basic Research Development Program (Grant
G2000077506), The Ministry of Education of China, and
Natural Science Foundation of Tianjin are gratefully
acknowledged.
N-Di[(R)-1-p h en yleth yl]-[(R)-1,1′-sp ir obiin d a n e-7,7′-d iyl]-
p h osp h or a m id ite (R,R,R)-2. Ligand (R,R,R)-2 was synthesized
in 50% yield by the same procedure as that for 1c using di[(R)-
J O026611M
1584 J . Org. Chem., Vol. 68, No. 4, 2003