Stereoselective synthesis of cyclic ethers using vinylogous sulfonates as radical acceptors: Effect of E/Z geometry and temperature on diastereoselectivity

Article abstract of DOI:10.1021/jo991970b

Treatment of the E-vinylogous sulfonates 1a-g with tris(trimethylsilyl)silane and triethylborane, in the presence of air, furnished the cyclic ethers 2/3a-g with good to excellent diastereoselectivity favoring the cis-isomer 2. This study demonstrated the level of stereocontrol in a 6-exo radical cyclization and may be attributed to the type of radical intermediate. Hence, the modest selectivity obtained for the cyclization of 1e may be a function of the acyl radical geometry (sp²) and high inversion barrier (29 kcal/mol) as compared to the alkyl (1 kcal/mol) and vinyl (2.9 kcal/mol) radicals. This is consistent with the acyl radical cyclization having an earlier transition state than the corresponding alkyl and vinyl radicals. The modest diastereoselectivity can be improved dramatically using the Z-vinylogous sulfonate (≥34:1; R = Ph) to promote kinetic trapping of the s-trans rotamer I and III, respectively (Figure 1). The 5-exo alkyl radical cyclization reaction under nonreductive Keck-allylation conditions was also examined, in which 8 was formed in 91% overall yield. This transformation provides a convenient method for in situ homologation and should be applicable to target directed synthesis.

Full text of DOI:10.1021/jo991970b

J . Org. Chem. 2000, 65, 4523-4528
4523
Ster eoselective Syn th esis of Cyclic Eth er s Usin g Vin ylogou s
Su lfon a tes a s Ra d ica l Accep tor s: Effect of E/Z Geom etr y a n d
Tem p er a tu r e on Dia ster eoselectivity
P. Andrew Evans* and Thara Manangan
Brown Laboratory, Department of Chemistry and Biochemistry, University of Delaware,
Newark, Delaware 19716
paevans@udel.edu
Received December 28, 1999
Treatment of the E-vinylogous sulfonates 1a -g with tris(trimethylsilyl)silane and triethylborane,
in the presence of air, furnished the cyclic ethers 2/3a -g with good to excellent diastereoselectivity
favoring the cis-isomer 2. This study demonstrated the level of stereocontrol in a 6-exo radical
cyclization and may be attributed to the type of radical intermediate. Hence, the modest selectivity
obtained for the cyclization of 1e may be a function of the acyl radical geometry (sp2) and high
inversion barrier (29 kcal/mol) as compared to the alkyl (1 kcal/mol) and vinyl (2.9 kcal/mol) radicals.
This is consistent with the acyl radical cyclization having an earlier transition state than the
corresponding alkyl and vinyl radicals. The modest diastereoselectivity can be improved dramatically
using the Z-vinylogous sulfonate (g34:1; R ) Ph) to promote kinetic trapping of the s-trans rotamer
I and III, respectively (Figure 1). The 5-exo alkyl radical cyclization reaction under nonreductive
Keck-allylation conditions was also examined, in which 8 was formed in 91% overall yield. This
transformation provides a convenient method for in situ homologation and should be applicable to
target directed synthesis.
In tr od u ction
We decided to extend our studies to vinylogous sulfonates
(VINS)7,8 since we anticipated that the sulfone would
allow alternative modes of functionalization for the cyclic
ether intermediate.9
Cyclic ether containing natural products represent both
architecturally challenging and biologically important
molecules that have stimulated the development of an
array of methods for their stereocontrolled syntheses.1,2
Methods that utilize radicals as reactive intermediates
have gained considerable prominence in recent times,
primarily due to the excellent stereocontrol that can be
obtained. Furthermore, the design and implementation
of tandem-reaction sequences that allow the construction
of multiple carbon-carbon bonds provides additional
versatility to this methodology.3 In a program directed
towards the synthesis of cyclic ether containing natural
products,4 we had examined the merit of vinylogous
carbonates5,6 in a series of intramolecular cyclizations.
(4) For an example of an acyl radical cyclization in the total
synthesis of (-)-kumausallene, see: Evans, P. A.; Murthy, V. S.;
Roseman, J . D.; Rheingold, A. L. Angew. Chem., Int. Ed. 1999, 38, 3175.
(5) (a) Evans, P. A.; Roseman, J . D. Tetrahedron Lett. 1995, 36, 31.
(b) Evans, P. A.; Roseman, J . D. J . Org. Chem. 1996, 61, 2252. (c)
Evans, P. A.; Roseman, J . D.; Garber, L. T. J . Org. Chem. 1996, 61,
4880 and pertinent references therein.
(6) For some representative examples of cyclic ethers construction
using intramolecular radical cyclizations, see: (a) Ueno, Y.; Chino.;
Watanabe, M.; Moriya, O.; Okawara, M. J . Am. Chem. Soc. 1982, 104,
5564. (b) Stork, G.; Mook, R., J r.; Biller, S. A.; Rychnovsky, S. D. J .
Am. Chem. Soc. 1983, 105, 3741. (c) Hutchinson, J . H.; Pattenden, G.;
Myers, P. L. Tetrahedron Lett. 1987, 28, 1313. (d) Lolkema, L. D. M.;
Hiemstra, H.; Al Ghouch, A. A.; Speckamp, W. N. Tetrahedron Lett.
1991, 32. 1491. (e) Rawal, V. H.; Singh, S. P.; Dufour, C.; Michoud, C.
J . Org. Chem. 1993, 58, 7718. (f) Ogura, K.; Kayano, A.; Fujino, T.;
Sumitani, N.; Fujita, M. Tetrahedron Lett. 1993, 34, 8313. (g) Burke,
S. D.; J ung, W.-J . Tetrahedron Lett. 1994, 35, 5837. (h) Ryu, I.;
Kurihara, A.; Muraoka, H.; Tsunoi, S.; Kambe, N.; Sonoda, N. J . Org.
Chem. 1994, 59, 7570. (i) Dulce`re, J .-P.; Dumez, E.; Faure, R. J . Chem.
Soc., Chem. Commun. 1995, 897. (j) Maiti, G.; Adhikari, S.; Roy, S. C.
J . Chem. Soc., Perkin Trans. 1 1995, 927. (k) Srikrishna, A.; Viswa-
janani, R.; Yelamaggad, C. V. Tetrahedron Lett. 1995, 36, 1127. (l)
Hartung, J .; Gallou, F. J . Org. Chem. 1995, 60, 6706. (m) Lee, E.; Park,
C.-P.; Yun, J . S. J . Am. Chem. Soc. 1995, 117, 8017. (o) Ihara, M.;
Katsumata, A.; Setsu, F.; Tokunaga, Y.; Fukumoto, K. J . Org. Chem.
1996, 61, 677. (p) Engman, L.; Gupta, V. J . Org. Chem. 1997, 62, 157.
(q) Beckwith, A. L. J .; Page, D. M. J . Org. Chem. 1998, 63, 5144. (i)
Hori, N.; Matsukura, H.; Matsuo, G.; Nakata, T. Tetrahedron Lett.
1999, 40, 2811 and pertinent references therein.
(1) (a) Doblem, M. Ionophores and Their Structures; Wiley-Inter-
science: New York, 1981. (b) Westley, J . W., Ed. Polyether Antibiotics;
Marcel Dekker: New York, 1982; Vols. I and II. (c) Erickson, K. L. In
Marine Natural Products; Scheuer, P. J ., Ed.; Academic Press: New
York, 1983; Vol. 5, Chapter 4, pp 131-257.
(2) For recent reviews on cyclic ether syntheses, see: (a) Boivin, T.
L. B. Tetrahedron 1987, 43, 3309. (b) Moody, C. J .; Davies, M. In
Studies in Natural Product Chemistry; Atta-ur-Rahman, Ed.; Elsevi-
er: Amsterdam, 1992; Vol. 10, pp 201-239. (c) Harmange, J .-C.;
Figade`re, B. Tetrahedron: Asymmetry 1993, 4, 1711. (d) Alvarez, E.;
Candenas, M.-L.; Perez, R.; Ravelo, J . L.; Martin, J . D. Chem. Rev.
1995, 95, 1953. (e) Hoberg, J . O. Tetrahedron 1998, 54, 12631.
(3) (a) Giese, B. Radicals in Organic Synthesis: Formation of
Carbon-Carbon Bonds, Pergamon Press: Oxford, 1986. (b) J asperse,
C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91, 1237. (c)
Motherwell, W. B.; Crich, D. Free Radical Chain Reactions in Organic
Synthesis; Academic Press: San Diego, 1992. (d) Curran, D. P. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1992; Vol. 4. (e) Ryu, I.; Sonoda, N.; Curran, D. P.
Chem. Rev. 1996, 96, 177. (f) Chatgilialoglu, C.; Crich, D.; Komatsu,
M.; Ryu, I. Chem. Rev. 1999, 99, 1991 and pertinent references therein.
(7) (a) Evans, P. A.; Roseman, J . D. Tetrahedron Lett. 1997, 38, 5249.
(b) Evans, P. A.; Manangan, T. Tetrahedron Lett. 1997, 38, 8165.
(8) Nicolaou, K. C.; Pfefferkorn, J . A.; Kim, S.; Wei, H. X. J . Am.
Chem. Soc. 1999, 121, 4724.
(9) Simpkins, N. S.; In Sulphones in Organic Synthesis; Pergamon
Press: New York, 1993.
10.1021/jo991970b CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/27/2000

4524 J . Org. Chem., Vol. 65, No. 15, 2000
Evans and Manangan
Sch em e 1
Herein, we describe a full account of the intramolecular
addition of acyl, alkyl, and vinyl radicals to vinylogous
sulfonates (eq 1). In the course of this study, we provide
The vinyl bromide 1d was prepared in a single step
from the known secondary alcohol 7 in 92% yield (eq 2),16
completing the synthesis of the substrates required for
the cyclization study. Table 1 provides a summary of the
results from this study.
evidence to support the hypothesis that acyl radicals
proceed through earlier transition states than the cor-
responding alkyl and vinyl radicals to explain the er-
roneous stereochemical result in the 6-exo acyl radical
cyclization. Our expectation that the Z-vinylogous sul-
fonate would dramatically improve the level of diaste-
reocontrol, through the kinetic trapping of the s-trans III
rotamer (Figure 1), provides a convenient method for
improving poor stereocontrol in this type of radical
cyclization.7,10
Tetr a h yd r ofu r a n Con str u ction . Treatment of the
vinylogous sulfonates 1a ,b with tris(trimethylsilyl)-
silane17 and triethylborane at room temperature, in the
presence of air, furnished the 2,5-disubstituted tetrahy-
drofurans 2/3a ,b in 87-99% yield, with excellent dias-
tereoselectivity, favoring the cis-isomer (Table 1; entries
1 and 2). The stereochemical outcome for the cyclization
reactions is consistent the Beckwith Transition State
Model, which has been used extensively to predict the
outcome of 5-hexenyl type radical cyclizations.18 The
cyclization was also extended to the Keck-type allyla-
tion,19 which facilitates the tandem formation of two new
carbon-carbon bonds. Treatment of the alkyl halide 1a
with allyltributyltin and triethylborane at room temper-
ature, in the presence of air, furnished the cyclic ether 8
in 91% yield, epimeric (1.4:1) at the phenylsulfonyl group
(eq 3).10 This transformation provides a useful method
for homologation, and should allow the introduction of
various side chains in a single operation, thus avoiding
Resu lts a n d Discu ssion
Scheme 1 summarizes the synthetic routes utilized for
the preparation of the alkyl bromides and acyl selenides
required for the cyclization study. Treatment of the
secondary alcohols 4a -c with lithium hexamethyldisilyl
azide, followed by E-bis(phenylsulfonyl)-1,2-ethylene 5a ,
furnished the corresponding E-vinylogous sulfonates
6a -c in excellent yield.11 Oxidation of the primary tert-
butyldimethylsilyl ethers 6a -c with J ones reagent fur-
nished the corresponding carboxylic acids,12 which were
then converted to the acyl selenides 1b, 1e, and 1g using
the Crich protocol in 68-93% overall yield.13 The alkyl
bromides were also available from the vinylogous sul-
fonates 6a -c via acid-catalyzed removal of the tert-butyl-
dimethylsilyl ether, followed by the treatment of the
primary alcohol with N-bromosuccinimide and triph-
enylphosphine to afford the alkyl bromides 1a ,14 1c, and
1f in 36-86% overall yield from 6.15
(14) The vinylogous sulfonate 1a could also be prepared via the
following reaction sequence. Treatment of the diol i with N-bromo-
succinimide at 0 °C afforded the primary bromide, which was then
converted to the E-vinylogous sulfonate 1a in an improved 53% overall
yield.
(15) Tius, M. A.; Fauq, A. H. J . Am. Chem. Soc. 1986, 108, 1035.
(16) Yuasa, Y.; Kano, S.; Shibuya, S. Heterocycles 1991, 32, 2311.
(17) For a recent review on this reagent, see: Chatgilialoglu, C.
Chem. Rev. 1995, 60, 3826.
(18) Beckwith, A. L. J .; Easton, C. J .; Lawrence, T.; Serelis, A. K.
Aust. J . Chem. 1983, 36, 545.
(19) For the early development of this reaction, see: (a) Keck, G.
E.; Yates, J . B. J . Am. Chem. Soc. 1982, 104, 5829. (b) Keck, G. E.;
Yates, J . B. J . Org. Chem. 1982, 47, 3590.
(10) Curran, D. P.; Porter, N. D.; Giese, B. In Stereochemistry of
Radical Reactions: Concepts, Guidelines and Synthetic Applications;
VCH Publishers: New York, 1995; pp 77-81.
(11) Meek, J . S.; Fowler, J . S. J . Org. Chem. 1968, 33, 985.
(12) Evans, P. A.; Roseman, J . D.; Garber, L. T. Synth. Commun.
1996, 26, 4685.
(13) Batty, D.; Crich, D. Synthesis 1990, 273.

Stereoselective Synthesis of Cyclic Ethers
J . Org. Chem., Vol. 65, No. 15, 2000 4525
Ta ble 1. In tr a m olecu la r Ra d ica l Cycliza tion s of th e Vin ylogou s Su lfon a tes (VINS) 1a -g
cyclic ethers
vinylogous sulfonate (VINS) 1a
entry
temp
conc,b M
ratio of 2:3c
yield (%)d
1
2
3
4
5
6
7
8
9
1a
1b
1c
1c
1d
1d
1e
1e
1f
n ) 0
n ) 0
n ) 1
n ) 1
n ) 1
n ) 1
n ) 1
n ) 1
n ) 2
n ) 2
X ) Br
Y ) H2
Y ) O
Y ) H2
Y ) H2
Y ) CH2
Y ) CH2
Y ) O
Y ) O
Y ) H2
Y ) O
rt
rt
rt
∆
rt
∆
rt
∆
rt
rt
0.02
0.02
0.01
0.01
0.01
0.01
0.01
0.01
0.005
0.005
g19:1
17:1
99
87
90
89
90
95
90
95
34
63
X ) SePh
X ) Br
g19:1
g19:1
g19:1
g19:1
6:1
3:1
g19:1
17:1
X ) Br
X ) Br
X ) Br
X ) SePh
X ) SePh
X ) Br
10
1g
X ) SePh
a
All the cyclizations were carried out on a 0.3 mmol reaction scale. b (TMS)3SiH, Et3B, PhH. c Ratios of diastereoisomers were determined
by 400 MHz 1H NMR integration. Isolated yields.
d
Sch em e 2
the alternative multistep sequences and carbanion medi-
ated functionalization which leads to ring-opening through
â-elimination.8
Tetr a h yd r op yr a n Con str u ction . The synthesis of
tetrahydropyrans was initiated by treating the vinylogous
sulfonates 1c,d under analogous conditions, both at
reflux and room temperature, to furnish the 2,6-disub-
stituted tetrahydropyrans 2/3c,d in 89-95% yield, with
excellent diastereoselectivity favoring the cis-isomer
(Table 1; entries 3-6). However, the poor diastereocontrol
in the 6-exo-trigonal acyl radical cyclization of 1e (entry
7 and 8) was attributed to kinetic trapping of the s-cis
rotamer II, as outlined in Figure 1, analogous to the
vinylogous carbonates.5b Despite the fact that the mixture
could be equilibrated to the thermodynamically more
stable diastereoisomer 2e, using a catalytic amount of
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in refluxing
6-exo acyl radical cyclization.20 This study would deter-
mine whether the s-trans III rotamer could be promoted
over the corresponding s-cis IV rotamer.10 To this end,
the secondary alcohol 9 was converted to the E- and
Z-vinylogous sulfonates 10a and 10b using lithium
hexamethyldisilyl azide (Scheme 2), followed by the
addition of the E- or Z-bis(phenylsulfonyl)-1,2-ethylene
5a or 5b, respectively.11 The primary tert-butyldimeth-
ylsilyl ethers 10a and 10b were then oxidized with J ones
reagent to the corresponding carboxylic acids12 and
converted to the acyl selenides 11a and 11b using the
Crich protocol in 71% overall yield in each case.13
benzene, the additional step and low recovery deemed it
unsuitable for synthetic purposes.
Treatment of the acyl selenides 11a and 11b, under
the standard cyclization conditions furnished the cyclic
ethers 12/13 in good yield, with 7:1 and g35:1 cis-
diastereoselectivity (Table 2, entries 1-2), thus confirm-
ing the relevance of the vinylogous sulfonate geometry
F igu r e 1.
The ability to prepare E- and Z-vinylogous sulfonates
provided an opportunity to test the hypothesis, that the
rotamer population could be altered using the acceptor
geometry and thus improve the diastereoselectivity in the
(20) Hanessian, S.; Dhanoa, D. S.; Beaulieu, P. L. Can. J . Chem.
1987, 65, 1859.

4526 J . Org. Chem., Vol. 65, No. 15, 2000
Evans and Manangan
Ta ble 2. In tr a m olecu la r Ra d ica l Cycliza tion s of th e E-
a n d Z-Vin ylogou s Su lfon a tes 11a /b
In conclusion, we have demonstrated the intramolecu-
lar addition of acyl, alkyl, and vinyl radicals to vinylogous
sulfonates for the efficient and stereoselective synthesis
of cis-disubstituted cyclic ethers. The stereochemical
outcome of the cyclization was confirmed with the aid of
NOE experiments and attributed to kinetic trapping of
the favored transition state I (n ) 0, 1, and 2) which has
the alkyl substituent pseudoequatorial with the vinylo-
gous sulfonate s-trans, to alleviate A1,3-allylic strain in
the transition state. The excellent regiochemical control
in the cyclization is a function of the intramolecular
addition of a nucleophilic radical to the LUMO of the
vinylogous sulfonate.22 The ability to utilize the Z-
vinylogous sulfonate to improve the diastereoselectivity,
by favoring III over IV, in the 6-exo-trigonal acyl radical
cyclization is particularly attractive for target-directed
synthesis (Figure 1).7a
cyclic ethers
ratio of
yield
(%)d
entry
VINS
11a
methodb
temp
12:13c
1
2
3
4
5
6
a
b
a
b
a
b
E
Z
E
Z
E
Z
A
A
A
A
B
B
rt
rt
∆
∆
∆
∆
7:1
35:1
5:1
34:1
5:1
85
84
80
82
83
83
34:1
a
All the cyclizations were carried out on a 0.3 mmol reaction
b
scale. Method A: (TMS)3SiH, Et3B, PhH. Method B: (TMS)3SiH,
AIBN, PhH. c Ratios of diastereoisomers were determined on crude
d
reaction mixtures by HPLC. Isolated yields.
to rotamer population. To further highlight the difference
in the diastereochemical outcome for the two isomers, the
cyclizations were repeated at elevated reaction temper-
ature. As expected, the Z-isomer 11b retains the very
high diastereoselectivity (34:1), while the E-isomer 11a
furnished the 2,6-disubstituted tetrahydropyran-3-ones
12/13 as a slightly lower 5:1 mixture of diastereoisomers
(entries 3 and 4). Finally, we decided to examine the
propensity for triethylborane to act as a Lewis acid
through chelation of the acyl or ring oxygen forcing the
vinylogous sulfonate to become s-cis II (Figure 1), by
repeating the cyclization with a noncoordinating initiator
(AIBN). Treatment of the acyl selenides 11a and 11b,
under the analogous reaction conditions, albeit with
catalytic AIBN as the initiator, furnished the cyclic ethers
12/13 with analogous selectivity (entries 5 and 6). Hence,
it appears the Lewis acidity of triethylborane plays a
minimal role in diastereochemical outcome of these
reactions.
Exp er im en ta l Section
1
Gen er a l. The chemical shifts of the H NMR and 13C NMR
spectra were all recorded relative to chloroform or benzene.
Multiplicities were determined with the aid of an APT
sequence, separating methylene and quaternary carbons ) e
(even), from methyl and methine ) o (odd). Melting points are
uncorrected. HPLC analysis was performed using a HP 1100
series HPLC system with a Zorbax RX-Sil column (4.6 mm ID
× 25 cm) eluting with 20% ethyl acetate in hexane. All
compounds were purified as specified, and gave spectroscopic
data consistent with being g95% the assigned structure.
Analytical TLC was carried out on precoated 0.2 mm thick
Merck 60 F254 silica plates. Flash chromatography was carried
out using Merck Silica Gel 60 (230-400 mesh).
All reagents and starting materials were obtained from
commercial suppliers (Acros, Aldrich, Fluka, and Lancaster)
and were used without purification except where indicated.
Dichloromethane was dried over and freshly distilled from
calcium hydride. All reactions were carried out under an inert
atmosphere of nitrogen using oven-dried or flame-dried glass-
ware unless specified to the contrary.
Gen er a l Cycliza tion P r oced u r e. The acyl selenide, alkyl
bromide, or vinyl bromide (0.3 mmol, azeotroped with anhy-
drous benzene) were dissolved in anhydrous benzene (see note
1) and cooled with stirring to 5 °C protected from moisture by
a drying tube packed with Drierite. Triethylborane (0.6 mL,
0.6 mmol, 2.0 equiv of a 1 M solution in hexane) was added
via syringe, followed by the addition of tris(trimethylsilyl)-
silane (190.8 µL, 0.6 mmol, 2.0 equiv). The mixture then was
allowed warmed to room temperature and stirred under the
atmosphere of dry air (TLC control). The solvent was then
removed in vacuo to afford a crude oil. Purification by flash
chromatography on silica gel (eluting with 10-20% ethyl
acetate/hexane) furnished the cyclic ethers 2/3 as colorless oils.
Additional insight into the low diastereocontrol was
also gleaned from high level ab initio calculations (MP2/
6-311G**) on the acyl radical (CH3CO.).21 These calcula-
tions indicate that the acyl radical is an sp2-hybridized
species with a barrier to inversion of 29 kcal/mol.
Conversely, the corresponding alkyl and vinyl radicals
have significantly lower barriers to inversion, 1 and 2.9
kcal/mol, respectively.3 It is therefore plausible that acyl
radicals commit to bond formation significantly earlier
than the corresponding alkyl and vinyl radicals. This
trend is also apparent in the 5- and 7-exo radical
cyclizations summarized in Table 1 (entries 1/2 and 9/10).
Tetr a h yd r ooxep in e Con str u ction . The synthesis of
2,7-disubstituted tetrahydrooxepines 2/3f,g was also
investigated. Treatment of the acyl selenides 1f,g with
tris(trimethylsilyl)silane17 and triethylborane, in the
presence of air, at room temperature afforded the 2,7-
disubstituted tetrahydrooxepines 2/3f,g in 34-63% yield,
and with excellent diastereoselectivity (Table 1, entries
9-10). Interestingly, in the acyl radical cyclization the
predominant byproduct was the aldehyde, formed from
the direct reduction of the acyl radical intermediate. This
provides another illustration of the effectiveness of the
low-temperature reaction conditions for suppression of
decarbonylation in demanding cyclization reactions of
this nature.5b The vinylogous sulfonates, however, appear
to be less efficient radical acceptors compared to the
vinylogous carbonate from the relative efficiency of the
cyclization reactions.
Note 1: The concentrations of the various ring sizes were
0.2, 0.1, and 0.05 M for five-, six-, and seven-membered rings,
respectively.
(2S*,5S*)-[(5-Met h yloxola n -2-yl)m et h yl]su lfon ylb en -
zen e (2a ). IR (CHCl3) 3024 (m), 2974 (m), 2930 (m), 2875 (m)
cm-1; 1H NMR (400 MHz, CDCl3) δ 7.92-7.89 (m, 2H), 7.64-
7.60 (m, 1), 7.55-7.51 (m, 2H), 4.22 (pentet, J ) 6.5 Hz, 1H),
3.92-3.84 (m, 1H), 3.42 (dd, A of ABX, J AB ) 14.1, J AX ) 5.8
Hz, 1H), 3.20 (dd, B of ABX, J AB ) 14.1, J BX ) 6.6 Hz, 1H),
2.14-2.05 (m, 1H), 1.99-1.91 (m, 1H), 1.77-1.69 (m, 1H),
1.45-1.36 (m, 1H), 1.07 (d, J ) 6.1 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 139.94 (e), 133.62 (o), 129.07 (o), 128.13 (o),
(22) The LUMO of a vinyl sulfone and a vinyl ether are known to
have larger coefficients at the â- and R-carbons, respectively, thus
reinforcing each other in R-alkoxy vinyl sulfone. See: (a) Sims, J .;
Houk, K. N. J . Am. Chem. Soc. 1973, 95, 5798. (b) Fleming, I. Frontier
Orbitals and Organic Chemical Reactions; J ohn Wiley and Sons: New
York, 1977; p 186.
(21) Guerra, M. J . Chem. Soc., Perkin Trans. 2 1996, 779.

Stereoselective Synthesis of Cyclic Ethers
J . Org. Chem., Vol. 65, No. 15, 2000 4527
75.83 (o), 72.86 (o), 61.80 (e), 32.37 (e), 31.49 (e), 21.10 (o);
HRMS (FAB, M+Na+) calcd for C12H16O3NaS 263.0718, found
263.0726.
140.30 (e), 133.64 (o), 129.18 (o), 127.85 (o), 82.11 (o), 80.61
(o), 58.26 (e), 42.04 (e), 38.46 (e), 22.20 (e), 22.16 (o); HRMS
(EI, M+) calcd for C14H19O4S 283.1004, found 283.1017.
(2S*,6R*)-6-P h en yl-2-[(p h en ylsu lfon yl)m et h yl]-4,5,6-
tr ih yd r o-2H-p yr a n -3-on e (12). IR (CHCl3) 3067 (m), 3028
(s), 2933 (m), 2857 (w), 1732 (vs), 1686 (m) cm-1; 1H NMR (400
MHz, CDCl3) δ 7.82-7.80 (m, 2H), 7.45 (t, J ) 7.5 Hz, 1H),
7.31 (t, J ) 7.8 Hz, 2H), 7.26-7.04 (m, 3H), 7.04-7.01 (m, 2H),
4.78 (dd, J ) 11.1, 2.4 Hz, 1H), 4.67 (dd, J ) 8.7, 2.4 Hz, 1H),
3.88 (dd, A of ABX, J AB ) 15.2, J AX ) 2.5 Hz, 1H), 3.47 (dd, A
of ABX, J AB ) 15.2, J AX ) 8.7 Hz, 1H), 2.70-2.66 (m, 2H),
2.35-2.29 (m, 1H), 2.17-2.06 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 203.60 (e), 140.19 (e), 139.72 (e), 133.36 (o), 128.88
(o), 128.26 (o), 128.01 (o), 127.84 (o), 125.59 (o), 78.57 (o), 78.53
(o), 56.24 (e), 37.94 (e), 34.13 (e); HRMS (FAB, M + Na+) calcd
for C18H18O4NaS 353.0824, found 353.0826.
(2S*,5S*)-5-Met h yl-2-[(p h en ylsu lfon yl)m et h yl]-2,4,5-
tr ih yd r ofu r a n -3-on e (2b). mp 143-144 °C; IR (CDCl3) 3018
(s), 2981 (w), 2932 (w), 1764 (s) cm-1 1H NMR (400 MHz,
;
CDCl3) δ 7.94-7.92 (m, 2H), 7.66-7.52 (m, 3H), 4.28-4.20 (m,
1H), 4.18 (dd, J ) 7.9, 2.6 Hz, 1H), 3.57 (dd, A of ABX, J AB
14.8, J AX ) 2.7 Hz, 1H), 3.34 (dd, B of ABX, J AB ) 14.8, J BX
)
)
8.0 Hz, 1H), 2.58 (dd, A of ABX, J AB ) 18.0, J AX ) 7.7 Hz,
1H), 2.14 (dd, B of ABX, J AB ) 18.0, J BX ) 10.3 Hz, 1H), 1.36
(d, J ) 6.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 212.70 (e),
139.86 (e), 133.83 (o), 129.11 (o), 128.17 (o), 76.26 (o), 72.86
(o), 57.37 (e), 43.22 (e), 20.65 (o); HRMS (EI, M+) calcd for
C
12H14O4S 254.0613, found 254.0602.
(2S*,6S*)-[(6-Meth ylp er h yd r o-2H-p yr a n -2-yl)m eth yl]-
su lfon ylben zen e (2c). mp 62-63 °C; IR (CHCl3) 3071 (w),
(1R/S)-1-(2S*,5S*)-[(5-Meth yloxolan -2-yl)bu t-3-en yl]su l-
fon ylben zen e (8). The alkyl bromide 1a (95.7 mg, 0.30 mmol,
azeotroped with anhydrous benzene) was dissolved in anhy-
drous benzene (3.0 mL) and cooled with stirring to 5 °C
protected from moisture by a drying tube packed with Drierite.
Triethylborane (360 µL, 0.36 mmol, 1.2 equiv of a 1 M solution
in hexane) was added via syringe, followed by the addition of
allyltributyltin (287.7 µL, 0.90 mmol, 3.0 equiv). The reaction
mixture was then warmed to room temperature and stirred
under the atmosphere of dry air for ca. 2 h (TLC control; 3:7
ethyl acetate/hexane). The solvent was then removed in vacuo
to afford a crude oil. Purification by flash chromatography on
silica gel (eluting with 5-10% ethyl acetate/hexane) furnished
the cyclic ether 8 (75.8 mg, 91%) as a colorless oil: IR (CHCl3)
1
3025 (m), 2976 (m), 2939 (m), 2848 (m) cm-1; H NMR (400
MHz, CDCl3) δ 7.92-7.89 (m, 2H), 7.63-7.58 (m, 1H), 7.53-
7.49 (m, 2H), 3.87 (dddd, J ) 11.5, 8.2, 3.2, 2.2 Hz, 1H), 3.36
(dd, A of ABX, J AB ) 14.6, J AX ) 8.2 Hz, 1H), 3.29-3.24 (tq, J
) 6.2, 2.0 Hz, 1H), 3.12 (dd, B of ABX, J AB ) 14.6, J BX ) 3.3
Hz, 1H), 1.81-1.75 (m, 1H), 1.64-1.58 (m, 1H), 1.55-1.43 (m,
2H), 1.26-1.16 (m, 1H), 1.09-0.98 (m, 1H), 0.82 (d, J ) 6.2
Hz, 3H); 13C NMR (100, MHz, CDCl3) δ 140.51 (e), 133.34 (o),
128.79 (o), 128.26 (o), 73.96 (o), 72.45 (o), 62.24 (e), 32.38 (e),
30.83 (e), 23.25 (e), 21.44 (o); HRMS (CI, M + NH4+) calcd for
C
13H22NO3S 272.1320, found 272.1334.
(2S*,6S*)-[(6-Meth yl-3-m eth ylen e-4,5,6-tr ih yd r o-2H-p y-
r a n -2-yl)m eth yl]su lfon ylben zen e (2d ). mp 73-74 °C; IR
(CHCl3) 3071 (w), 3026 (m), 2976 (m), 2918 (m), 2848 (m), 1655
3070 (m), 3029 (m); 2972 (s), 2930 (s), 2875 (s), 1641 (m) cm-1
;
(w) cm-1
;
1H NMR (400 MHz, CDCl3) δ 7.92-7.89 (m, 2H),
1H NMR (400 MHz, CDCl3) δ 7.87-7.84 (m, 2H), 7.61-7.46
(m, 3H), 5.84-5.69 (m, 1H), 5.02-4.92 (m, 2H), 4.32-4.27 (m,
0.6H), 4.19-4.14 (m, 0.4H), 3.90-3.76 (m, 1H), 3.32 (q, J )
5.7 Hz, 0.4H), 3.16 (dt, J ) 5.7, 4.8 Hz, 0.6H), 2.69-2.43 (m,
2H), 2.05-1.76 (m, 3H), 1.39-1.28 (m, 1H), 1.08 (d, J ) 6.1,
1.8H), 0.97 (d, J ) 6.0, 1.2H); 13C NMR (100 MHz, C6D6) δ
141.69 (e), 140.22 (e), 135.95 (o), 135.90 (o), 133.49 (o), 133.26
(o), 129.84 (o), 129.50 (o), 129.47 (o), 129.07 (o), 129.03 (o),
128.99 (o), 117.36 (e), 117.30 (e), 77.07 (o), 76.57 (o), 75.64 (o),
75.50 (o), 69.28 (o), 68.18 (o), 33.21 (e), 32.99 (e), 30.97 (e),
30.87 (e), 29.97 (e), 28.33 (e), 21.21 (o), 20.97 (o); HRMS (CI,
M+) calcd for C15H24NO3S 298.1477, found 298.1466.
7.61-7.56 (m, 1H), 7.52-7.48 (m, 2H), 4.78 (d, J ) 1.8 Hz,
1H), 4.62 (s, 1H), 4.32 (dd, J ) 8.1, 3.6 Hz, 1H), 3.54-3.42 (m,
3H), 2.34 (ddd, A of ABXY, J AB ) 13.8, J AX ) 4.7, J AY ) 2.5
Hz, 1H), 2.26-2.18 (m, 1H), 1.63 (dp, J ) 13.1, 2.4 Hz, 1H),
1.27-1.17 (m, 1H), 0.77 (d, J ) 6.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 144.12 (e), 140.70 (e), 133.28 (o), 128.71 (o),
128.31 (o), 107.46 (e), 73.87 (o), 73.47 (o), 58.62 (e), 35.05 (e),
33.17 (e), 20.82 (o); HRMS (EI, M + H+) calcd for C14H19O3S
267.1055, found 267.1058.
(2S*,6S*)-6-Met h yl-2-[(p h en ylsu lfon yl)m et h yl]-4,5,6-
tr ih yd r o-2H-p yr a n -3-on e (2e). mp 89-91 °C; IR (CHCl3)
3022 (s), 2980 (w), 2934 (w), 2858 (w), 1729 (s) cm-1; 1H NMR
(CDCl3) δ 7.91-7.89 (m, 2H), 7.64-7.60 (m, 1H), 7.54-7.51
(m, 2H), 4.43 (dd, J ) 8.7, 2.3 Hz, 1H), 3.83 (ddq, J ) 12.4,
6.2, 2.5 Hz, 1H), 3.81 (dd, J ) 15.1, 2.3 Hz, 1H), 3.30 (dd, J )
15.1, 8.7 Hz, 1H), 2.54 (ddd, A of ABXY, J AB ) 16.0, J AX ) 6.0,
P r oced u r e for P r ep a r in g th e E- a n d Z-Vin ylogou s
Su lfon a tes 10a a n d 10b. The secondary alcohol 9 (221.7 mg,
0.79 mmol) dissolved in anhydrous THF (7.0 mL) and cooled
with stirring to 0 °C. Lithium hexamethyldisilyl azide (1.00
mL, 1.00 mmol, 1.0 M solution in THF) was added dropwise
and the reaction stirred for ca. 30 min and then warmed to
room temperature where it was stirred for an additional 30
min. The reaction mixture was then cooled to 0 °C, and E-bis-
(phenylsulfonyl)-1,2-ethylene 5a (313.9 mg, 1.02 mmol, 1.3
equiv) added portionwise keeping the internal temperature e5
°C. The reaction mixture was then allowed to warm to room
temperature where it was stirred for ca. 3 h (TLC control; 3:7
ethyl acetate/hexane). The reaction mixture was then parti-
tioned between saturated aqueous NaHCO3 solution and
diethyl ether, the organic layers were combined, washed with
saturated aqueous NaCl solution, dried (Na2SO4), and filtered,
and the solvent removed in vacuo to afford a crude yellow oil.
Purification by flash chromatography on silica gel (eluting with
10-20% ethyl acetate/hexane) furnished the E-vinylogous
sulfonate 10a (345.8 mg, 98%) as a yellow oil. The Z-vinylogous
sulfonate 10b was prepared in an analogous manner using
the Z-bis(phenylsulfonyl)-1,2-ethylene 5b in 89% yield.
(1E)-2-[1-P h en yl-4-(ter t-bu tyld im eth ylsilyloxy)bu toxy]-
vin ylsu lfon ylben zen e (10a ). mp 48-49 °C; IR (CHCl3) 3071
(w), 3028 (m), 3019 (m), 2956 (m), 2930 (m), 2884 (m), 2857
(m) 1627 (s), 1608 (s) cm-1; 1H NMR (400 MHz, CDCl3) δ 7.73-
7.70 (m, 2H), 7.54-7.49 (m, 2H), 7.46-7.41 (m, 2H), 7.35-
7.27 (m, 3H), 7.21-7.19 (m, 2H), 5.66 (d, J ) 12.0 Hz, 1H),
4.90-4.87 (m, 1H), 3.58 (dt, J ) 6.2, 1.4 Hz, 2H), 2.04-1.94
(m, 1H), 1.90-1.82 (m, 1H), 1.62-1.42 (m, 2H), 0.84 (s, 9H),
-0.01 (6H, s); 13C NMR (100 MHz, CDCl3) δ 160.18 (o), 142.51
(e), 139.31 (e), 132.57 (o), 128.98 (o), 128.84 (o), 128.50 (o),
J AY ) 3.1 Hz, 1H), 2.46 (ddd, B of ABXY, J AB ) 16.0, J BX
)
12.2, J BY ) 6.7 Hz, 1H), 2.03 (ddt, J ) 13.7, 6.5, 2.9 Hz, 1H),
1.82-1.72 (m, 1H), 1.00 (d, J ) 6.1 Hz, 3H); 13C NMR (CDCl3)
δ 204.20 (e), 140.29 (e), 133.55 (o), 128.93 (o), 128.14 (o), 77.67
(o), 73.12 (o), 56.11 (e), 37.47 (e), 33.69 (e), 20.53 (o); HRMS
(EI, M + H+) calcd for C13H17O4S 269.0848, found 269.0854.
(2S*,7S*)-[(7-Met h yloxep a n -2-yl)m et h yl]su lfon ylben -
zen e (2f). mp 45-47 °C; IR (CHCl3) 3019 (s), 2933 (s), 2858
(m) cm-1 1H NMR (400 MHz, CDCl3) δ 7.93-7.89 (m, 2H),
;
7.63-7.59 (m, 1H), 7.55-7.51 (m, 2H), 4.12-4.06 (m, 1H),
3.57-3.49 (m, 1H), 3.48 (dd, A of ABX, J AB ) 14.7, J AX ) 8.9
Hz, 1H), 3.10 (dd, B of ABX, J AB ) 14.7, J BX ) 2.8 Hz, 1H),
1.78-1.35 (m, 8H), 0.74 (d, J ) 6.3 Hz, 3H); 13C NMR (100,
MHz, CDCl3) δ 140.67 (e), 133.31 (o), 129.03 (o), 127.75 (o),
75.90 (o), 73.33 (o), 62.61 (e), 37.52 (e), 36.08 (e), 26.11 (e),
23.35 (e), 22.03 (o); HRMS (EI, M+) calcd for C14H20O3S
268.1133, found 268.1131.
(2S*,7S*)-7-Meth yl-2-[(p h en ylsu lfon yl)m eth yl]oxep a n -
3-on e (2 g). mp 112-113 °C; IR (CHCl3) 3033 (w), 2974 (w),
2934 (m), 2869 (w), 1714 (s) cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.93-7.90 (m, 2H), 7.65-7.61 (m, 1H), 7.57-7.52 (m, 2H),
4.42 (dd, J ) 9.4, 2.2 Hz, 1H), 3.61 (dd, A of ABX, J AB ) 14.7,
J AX ) 2.2 Hz, 1H), 3.59-3.51 (m, 1H), 3.38 (dd, B of ABX, J AB
) 14.8, J BX ) 9.4 Hz, 1H), 2.75 (ddd, A of ABXY, J AB ) 14.8,
J AX ) 12.3, J AY ) 2.5 Hz, 1H), 2.52-2.47 (ddt, J ) 14.8 Hz,
6.5, 1.4 Hz, 1H), 1.95-1.1.82 (m, 2H), 1.65-1.47 (m, 2H), 1.01
(d, J ) 6.2 Hz, 3H); 13C NMR (400 MHz, CDCl3) δ 212.17 (e),

4528 J . Org. Chem., Vol. 65, No. 15, 2000
Evans and Manangan
126.68 (o), 126.16 (o), 108.00 (o), 85.84 (o), 62.44 (e), 33.91 (e),
28.38 (e), 25.91 (o), 18.28 (e), -5.36 (o); HRMS (FAB, M + Na+)
calcd for C24H34O4NaSiS 469.1845, found 469.1827.
allowed to stir for ca. 20 min. The reaction mixture was then
concentrated in vacuo and further dried under high vacuum
for ca. 1 h. Phenylselenyl bromide (173.4 mg, 0.72 mmol, 2.0
equiv) was dissolved in anhydrous tetrahydrofuran (2.8 mL),
and the purple mixture was cooled with stirring to 0 °C.
Tributylphosphine (181.1 µL, 0.7 mmol, 2 equiv) was then
added slowly via syringe affording a canary yellow-colored
solution. The mixture was allowed to warm to room temper-
ature and stirred for 20 min, the triethylammonium salt was
added in anhydrous tetrahydrofuran (2.0 mL), and the reaction
mixture stirred at room temperature for ca. 19 h (TLC control;
5% AcOH in ethyl acetate). The reaction mixture was then
partitioned between saturated NaHCO3 and diethyl ether, and
the organic layers were combined, dried (Na2SO4), filtered, and
concentrated in vacuo to afford a crude oil. Purification by flash
chromatography on silica gel (eluting with 5 and then 30%
ethyl acetate/hexane) furnished the acyl selenide 11a (140 mg,
82%) as a pale yellow oil. The Z-isomer 11b was prepared in
an analogous fashion in 84% yield as a pale yellow oil.
4-[(1E)-2-(P h en ylsu lfon yl)vin yloxy]-4-p h en yl-1-p h e-
n ylselen obu ta n -1-on e (11a ). IR (CHCl3) 3070 (w), 3029 (m),
3012 (m), 2935 (w), 1716 (s), 1628 (s), 1609 (s) cm-1; 1H NMR
(400 MHz, CDCl3) δ 7.74-7.71 (m, 2H), 7.54-7.50 (m, 1H),
7.47-7.28 (m, 11H), 7.20-7.17 (m, 2H), 5.69 (d, J ) 12.1 Hz,
1H), 4.95 (dd, J ) 7.9, 5.4 Hz, 1H), 2.84-2.68 (m, 2H), 2.29-
2.03 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 199.47 (e), 159.49
(o), 142.11 (e), 138.10 (e), 135.65 (o), 132.62 (o), 129.33 (o),
128.90 (o), 128.94 (o), 126.75 (o), 126.61 (o), 125.92 (o), 125.86
(e), 108.59 (o), 83.66 (o), 42.76 (e), 32.35 (e); HRMS (EI, M+)
calcd for C24H23O4S78Se 485.0490, found 485.0504.
4-[(1Z)-2-(P h en ylsu lfon yl)vin yloxy]-4-p h en yl-1-p h e-
n ylselen obu ta n -1-on e (11b). IR (CHCl3) 3070 (m), 3027 (m);
3016 (m); 1715 (s); 1628 (s) 1609 (s) cm-1; 1H NMR (400 MHz,
CDCl3) δ 8.04-8.01 (m, 2H), δ 7.66-7.61 (m, 1H), 7.58-7.53
(m, 2H), 7.50-7.45 (m, 2H), 7.41-7.34 (m, 3H), 7.30-7.25 (m,
3H), 7.23-6.96 (m, 2H), 6.39 (d, J ) 6.4 Hz, 1H), 5.58 (d, J )
6.4 Hz, 1H), 4.85 (dd, J ) 8.0, 5.2 Hz, 1H), 2.78-2.63 (m, 2H),
2.17-2.03 (m, 2H); 13C NMR (400 MHz, CDCl3) δ 199.75 (e),
154.38 (o), 142.70 (e), 138.69 (e), 135.76 (o), 133.00 (o), 129.45
(o), 129.10 (o), 128.93 (o), 128.82 (o), 127.77 (o), 127.72 (o),
126.03 (e), 126.00 (o), 108.99 (o), 85.68 (o), 42.73 (e), 32.57 (e);
HRMS (EI, M+) calcd for C24H23O4S78Se 485.0490, found
485.0504.
(1Z)-2-[1-P h en yl-4-(ter t-bu tyld im eth ylsilyloxy)bu toxy]-
vin ylsu lfon ylben zen e (10b). mp 51-52 °C; IR (CHCl3) 3081
(m), 3067 (m), 3027 (m), 2955 (s), 2930 (s), 2858 (s), 1626 (vs)
cm-1; 1H NMR (400 MHz, CDCl3) δ 8.03-8.00 (m, 2H), 7.62-
7.57 (m, 1H), 7.53-7.48 (m, 2H), 7.27-7.23 (m, 3H), 6.99-
6.95 (m, 2H), 6.42 (d, J ) 6.5 Hz, 1H), 5.53 (d, J ) 6.4 Hz,
1H), 4.78 (dd, J ) 7.8, 5.7 Hz, 1H), 3.61-3.51 (m, 2H), 1.96-
1.75 (m, 2H), 1.55-1.34 (m, 2H), 0.86 (s, 9H), 0.01 (s, 6H); 13
C
NMR (100 MHz, CDCl3) δ 154.89 (o), 142.74 (e), 139.72 (e),
132.75 (o), 128.69 (o), 128.56 (o), 128.43 (o), 127.83 (o), 126.13
(o), 108.22 (o), 87.77 (o), 62.44 (e), 34.02 (e), 28.29 (e), 25.92
(o), 18.28 (e), -5.36 (o); HRMS (FAB, M + Na+) calcd for
C
24H34O4NaSiS 469.1845, found 469.1832.
Gen er a l J on es Oxid a tion P r oced u r e. The tert-butyldi-
methylsilyl ether 10a (188.7 mg, 0.42 mmol) was dissolved in
acetone (4.2 mL) and cooled with stirring to -10 °C. J ones
reagent (0.84 mL, 1.68 mmol, 2 M aqueous solution) was added
dropwise, and the reaction mixture was allowed to warm to
ambient temperature and stirred for ca. 16 h (TLC control;
7:3 ethyl acetate/hexane). Propan-2-ol (1.0 mL) was added
dropwise to destroy excess J ones reagent, the reaction mixture
was filtered through Celite and concentrated in vacuo to afford
the crude acid. The crude acid was partitioned between
saturated aqueous NaHCO3 solution and diethyl ether. The
aqueous layer was then cooled to 0 °C, carefully acidified with
an aqueous 1 N HCl solution, and extracted with ethyl acetate.
The organic layers were combined, washed with a saturated
NaCl solution, dried (Na2SO4), and filtered, and the solvent
was removed in vacuo to afford the carboxylic acid (127.9 mg,
87%) as a yellow oil. The Z-isomer 10b was treated in an
analogous manner to afford the carboxylic acid in 84% yield,
as a pale yellow oil.
4-[(1E)-2-(P h en ylsu lfon yl)vin yloxy]-4-p h en ylb u t a n o-
ic a cid . IR (CHCl3) 3600-2300 (bs), 3018 (s), 2927 (s), 2854
(m), 1772 (s), 1723 (s), 1688 (m) cm-1 1H NMR (400 MHz,
;
CDCl3) δ 7.73-7.70 (m, 2H), 7.54-7.41 (m, 4H), 7.36-7.28 (m,
3H), 7.22-7.20 (m, 2H), 5.70 (d, J ) 12.2 Hz, 1H), 4.97 (dd, J
) 7.7, 5.4 Hz, 1H), 2.49-2.34 (m, 2H), 2.28-2.07 (m, 2H); 13
C
NMR (100 MHz, CDCl3) δ 177.84 (e), 159.68 (o), 142.25 (e),
138.31 (e), 132.69 (o), 129.02 (o), 128.84 (o), 126.71 (o), 126.07
(o), 108.67 (o), 84.13 (o), 32.06 (e), 29.47 (e); HRMS (FAB, M
+ Na+) calcd for C18H18O5NaS 369.0773, found 369.0784.
4-[(1Z)-2-(P h en ylsu lfon yl)vin yloxy]-4-p h en ylb u t a n o-
ic a cid . IR (CHCl3) 3500-2300 (bs), 3026 (s), 2927 (m), 1713
(s), 1629 (s) cm-1; 1H NMR (400 MHz, CDCl3) δ 8.02-8.00 (m,
2H), 7.64-7.60 (m, 1H), 7.55-7.51 (m, 2H), 7.28-7.25 (m, 3H),
6.98-6.96 (m, 2H), 6.41 (d, J ) 6.5 Hz, 1H), 5.57 (d, J ) 6.5
Hz, 1H), 4.87 (dd, J ) 8.4, 4.7 Hz, 1H), 2.45-2.30 (m, 2H),
2.19-1.99 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 177.44 (e),
154.49 (o), 142.62 (e), 138.80 (e), 132.97 (o), 128.88 (o), 128.79
(o), 128.73 (o), 127.73 (o), 126.01 (o), 108.85 (o), 86.12 (o), 32.26
(e), 29.46 (e); HRMS (FAB, M + Na+) calcd for C18H18O5NaS
369.0773, found 369.0764.
Ack n ow led gm en t. We thank the National Insti-
tutes of Health (GM54623) for generous financial sup-
port. We also thank Zeneca Pharmaceuticals for an
Excellence in Research Award, Eli Lilly for a Young
Faculty Grantee Award, Glaxo Wellcome for a Chem-
istry Scholar Award, and the Camille and Henry Drey-
fus Foundation for a Camille Dreyfus Teacher-Scholar
Award (P.A.E.). The Development and Promotion of
Science and Technology Talents Project (DPST)-
Thailand is thanked for a Graduate Fellowship (T.M.).
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
Gen er a l P r oced u r e for Acyl Selen id e F or m a tion . The
carboxylic acid from 10a (121.8 mg, 0.35 mmol) was dissolved
in anhydrous dichloromethane (0.35 mL) and cooled with
stirring to 0 °C. Triethylamine (58.8 µL, 0.42 mmol, 1.2 equiv)
was added in anhydrous dichloromethane (0.7 mL) and the
mixture allowed to warm to room temperature where it was
cedures and spectra data for the preparation of compounds
1
1a -g, in addition to the H NMR spectra for compounds 1a -
g, 2a -g, 8, 10a /b, 11a /b, and 12. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O991970B