Simple and efficient method for the oxidation of sulfides to sulfoxides: Application to the preparation of glycosyl sulfoxides

Full text of DOI:10.1021/jo961478h

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J . Org. Chem. 1996, 61, 8347-8349
8347
Sch em e 1
Sim p le a n d Efficien t Meth od for th e
Oxid a tion of Su lfid es to Su lfoxid es:
Ap p lica tion to th e P r ep a r a tion of Glycosyl
Su lfoxid es
Ramesh Kakarla,* Richard G. Dulina,
Nicole T. Hatzenbuhler, Y. W. Hui, and Michael J . Sofia
sulfones has been studied extensively using various
oxidation protocols.9 However, the oxidation of glycosyl
sulfides to sulfoxides has primarily been achieved with
m-CPBA2,10 in CH2Cl2 (Scheme 1). Our investigation of
the large-scale m-CPBA oxidation of phenyl 2,3,4,6-tetra-
O-benzyl-1-thio-â-D-glucopyranoside (1) to provide the
corresponding sulfoxide (2) identified several drawbacks
to this method. The m-CPBA oxidation of glycosyl
sulfides to the corresponding sulfoxides is initiated at -78
°C and allowed to warm slowly to -30 °C. The low
temperature is required to avoid sulfone formation.
However, the reaction does not proceed to completion at
-78 °C and, consequently, warming is needed. In addi-
tion, m-CPBA is only partially soluble in CH2Cl2, and
complete removal of the byproduct m-chlorobenzoic acid
from the reaction mixture was difficult and often incom-
plete. During reaction workup at room temperature,
overoxidation of some sulfoxide product to the undesired
and unreactive sulfone was also problematic. Attempts
to quench the unspent oxidant before workup added
procedural complications to the process and introduced
concerns about sulfoxide to sulfide reduction. These
problems with m-CPBA oxidation of glycosyl sulfides
prompted us to investigate alternate oxidation protocols
that would be simple, mild, and efficient and afford
selective oxidation of glycosyl sulfides to sulfoxides at
room temperature without overoxidation to the corre-
sponding sulfone.
Transcell Technologies, Inc., 2000 Cornwall Road,
Monmouth J unction, New J ersey 08852
Received August 1, 1996
Compounds containing a sulfoxide moiety are useful
synthetic intermediates for the construction of various
chemically and biologically significant molecules.1 The
discovery by Kahne and co-workers2 of the anomeric
glycosyl sulfoxide as a novel glycosyl donor provided a
new and powerful method for chemical glycosylation.
Synthesis of a wide range of glycosides3 and oligosaccha-
rides4 have been reported using the Kahne sulfoxide
glycosylation methodology. Glycosyl sulfoxide donor
technology has been applied not only to solution-phase
glycosylations5 but also to the solid-phase synthesis of
carbohydrates.6 High R or â anomeric stereochemical
control with a variety of glycosyl acceptors has been
reported with this methodology.2 It was also determined
that the stereochemical outcome of the glycosylation is
independent of both the anomeric stereochemistry (R or
â) and the sulfoxide stereochemistry2,7 (R or S) in the
glycosyl donor. Consequently, glycosyl sulfoxide glyco-
sylation chemistry avoids the need for separation of
anomers and allows for the use of a diastereomeric
mixture of glycosyl sulfoxides.
In our efforts to develop glycosylated cholic acid
derivatives as drug transport reagents, it was desirable
to effect large-scale glycosylations using the glycosyl
sulfoxide glycosylation methodology.8 Consequently, ki-
logram quantities of various glycosyl sulfoxides were
required. The oxidation of sulfides to sulfoxides or
Resu lts a n d Discu ssion
We focused our efforts on inexpensive reagent systems
(Table 1) for developing a simplified method for the room
temperature oxidation of sulfides to sulfoxides. We also
chose the glycosyl sulfide 1 as our model substrate. Our
initial attempts to oxidize 1 using urea-H2O211 in AcOH/
THF (Table 1, entry 2) or in AcOH/CH2Cl2/MeOH (Table
1, entry 3) provided the sulfoxide 2 in 60% and 80% yield,
respectively. Replacing AcOH with Ac2O as the promoter
in combination with urea-H2O2 (Table 1, entry 4) gave
2 in 85% yield along with 15% of the sulfone. A recent
report on the oxidation of various aliphatic and aromatic
sulfides by tert-butyl hydroperoxide9g (TBHP) showed
that the reaction was accelerated by adding silica gel
(SiO2) as an adsorbent resulting in the rapid formation
* To whom correspondence should be addressed.
(1) (a) Field, L. Synthesis 1978, 713. (b) Block, E. Reactions of
Organosulfur Compounds; Academic: New York, 1978. (c) Durst, T.
in Comprehensive Organic Chemistry; Barton, D., Ollis, W. D., Eds.;
Pergman: Oxford, U.K., 1979; Vol. 3. (d) Solladie, G. Synthesis 1981,
185. (e) Ikemoto, N.; Schreiber, S. L. J . Am. Chem. Soc. 1990, 112,
9657. (f) Stork, G.; Kim, G. J . Am. Chem. Soc. 1992, 114, 1087. (g)
Berkowitz, D. B.; Schulte, G. K.; Danishefsky, S. J . Am. Chem. Soc.
1992, 114, 4518. (h) Moghaddam, F. M.; Ghaffarzadeh, M. Tetrahedron
Lett. 1996, 37, 1855.
(2) Kahne, D.; Walker, S.; Cheng, Y.; Van Engen, D. J . Am. Chem.
Soc. 1989, 111, 6881.
(3) Sliedregt, L. A.; Van Der Marel, G. A.; Van Boom, J . H.
Tetrahedron Lett. 1994, 35, 4015. (b) Alonso, I.; Khiar, N.; Martin-
Lomas, M. Tetrahedron Lett. 1996, 37, 1477.
(4) (a) Voelter, W.; Wang, Y.; Zhang, H. Tetrahedron Lett. 1995, 36,
1234; (b) Z. Naturforsch. 1995, 50b, 661. (c) Khiar, N.; Martin-Lomas,
M. J . Org. Chem. 1995, 60, 7017.
(5) (a) Yang, D.; Kim, S.-H.; Kahne, D. J . Am. Chem. Soc. 1991,
113, 4715. (b) Cheng, Y.; Ho, D. M.; Gottlieb, C. R.; Kahne, D.; Bruck,
M. A. J . Am. Chem. Soc. 1992, 114, 7319. (c) Kahne, D.; Raghavan, S.
J . Am. Chem. Soc. 1993, 115, 1580. (d) Kim, S.-H.; Augeri, D.; Yang,
D.; Kahne, D. J . Am. Chem. Soc. 1994, 116, 1766.
(9) (a) Patai, S., Rappoport, Z., Eds. The Chemistry of Sulphones,
Sulphoxides and Cyclic Sulphides; J ohn Wiley and Sons: Chichester,
U.K., 1994. (b) Uemura, S. In Comprehensive Organic Synthesis; Ley,
S. V., Ed.; Pergman: Oxford, 1991; Vol. 7, p 757. (c) Fabretti, A.; Ghelfi,
F.; Grandi, R.; Pagnoni, U. M. Synth. Commun. 1994, 24, 2393. (d)
Siedlecka, R.; Skarzewski, J . Synthesis 1994, 401. (e) Desmartean, D.
D.; Petrov, V. A.; Montanari, V.; Pregnolato, M.; Resnati, G. J . Org.
Chem. 1994, 59, 2762. (f) Adam, W.; Mitchell, C. M.; Saha-Moller, C.
R. Tetrahedron 1994, 50, 13121. (g) Breton, G. W.; Fields, J . D.; Kropp,
P. J . Tetrahedron Lett. 1995, 36, 3825. (h) Orito, K.; Hatakeyama, T.;
Takeo, M.; Suginome, H. Synthesis 1995, 1357. (i) Aldea, R.; Alper, H.
J . Org. Chem. 1995, 60, 8365. (j) Procter, D. J .; Thornton-Pett, M.;
Rayner, C. M. Tetrahedron Lett. 1996, 37, 1841. (k) Arterburn, J . B.;
Nelson, S. L. J . Org. Chem. 1996, 61, 2260. (l) Khanna, V.; Maikap,
G. C.; Iqbal, J . Tetrahedron Lett. 1996, 37, 3367.
(6) Yan, L.; Taylor, C. M.; Goodnow, R.; Kahne, D. J . Am. Chem.
Soc. 1994, 116, 6953.
(7) Walker, S. Ph.D. Dissertation, Princeton University, 1991.
(8) (a) Walker, S.; Sofia, M. J .; Kakarla, R.; Kogan, N. A.; Wierichs,
L.; Longley, C. B.; Brucker, K.; Axelrod, H. R.; Midha, S.; Babu, S.;
Kahne, D. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 1585. (b) Longely,
C. B.; Axelrod, H. R.; Midha, S.; Kakarla, R.; Kogan, N. A.; Sofia, M.
J .; Babu, S.; Wierichs, L.; Walker, S. Ann. N.Y. Acad. Sci. U.S.A. 1995,
772, 268. (c) Kakarla, R.; Kogan, N. A.; Dulina, R. G; Hui, Y. W.,
Hatzenbuhler, N. T.; Liu, D.; Chen, A.; Wagler, T.; Sofia, M. J . 211th
ACS National Meeting, New Orleans, 1996; Abstract No. 320 (Div. of
Org. Chem.).
(10) Schmidt, R. R.; Kast, J . Tetrahedron Lett. 1986, 27, 4007.
(11) Balicki, R.; Kaczmarek, L.; Nantki-Namirski, P. Liebigs Ann.
Chem. 1992, 883.
S0022-3263(96)01478-8 CCC: $12.00 © 1996 American Chemical Society

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8348 J . Org. Chem., Vol. 61, No. 23, 1996
Notes
Ta ble 1. Oxid a tion of Su lfid ea (1) to Su lfoxid eb (2) a t Room Tem p er a tu r e w ith Va r iou s Oxid izin g Rea gen ts a n d
Con d ition s
% yieldc
exp no.
reagent (mmol)
m-CPBA (1.1)
urea-H2O2 (1.5)
urea-H2O2 (1.5)/AcOH (2)
urea-H2O2 (1.5)/Ac2O (2)
urea-H2O2 (1.5)/AcOH (2)
(CH3)3CO2H (2)/AcOH (1)
(CH3)3CO2H (2)/AcOH (1)
H2O2 (2)
H2O2 (4.4)/CF3CO2H (1)
H2O2 (4.4)/Ac2O (1)
H2O2 (4.4)/Ac2O (2)
H2O2 (2.2)/AcOH (2)
H2O2 (1.2)/Ac2O (1.1)
solvent (10 mL)
CH2Cl2
AcOH, THF (2:1)
CH2Cl2, MeOH (2:1)
CH2Cl2, MeOH (2:1)
CH2Cl2, MeOH (4:1)
CH2Cl2
CH2Cl2
AcOH, THF (2:1)
THF
acetone
acetone
time(h)
sulfoxide
sulfone
trace
sulfide
1d
2
3
2
72
24
8
96
48
48
120
12
60
24
96
4
95
60
80
85
40
20
30
90
50
90
85
40
95
trace
40
20
trace
15
4
5e
6
60
80
70
10
30
10
10
60
7e
8e
9f
trace
10
trace
5
10
11
12e
13e
CH2Cl2
CH2Cl2
trace
a
b
d
1 mmol of sulfide was used. Mixture of R and S isomers. c Isolated yield. Reaction was done at -78 °C to -30 °C. e 200 mg of silica
gel (230-400 mesh) was used as an adsorbent. f 10% of unknown compound was also isolated and not characterized.
Ta ble 2. Oxid a tion of Su lfid es to Su lfoxid es Usin g H2O2,
Since our initial attempts with urea-H2O2 and TBHP
reagent systems failed to give acceptable yields of pure
a
Ac2O, a n d SiO2 in CH2Cl2
sulfide oxidation product 2, we turned our efforts toward
other H2O2-mediated oxidation protocols. Oxidation of
1 with 30% aqueous H2O2 in AcOH/THF (Table 1, entry
8) after 120 h gave 2 in 90% yield. Addition of TFA
accelerated the H2O2 oxidation of 1 (Table 1, entry 9),
but also resulted in the formation of sulfone (10%) and
an unidentified side product (10%). Addition of Ac2O
(Table 1, entry 10) to H2O2 provided 2 in 90% yield, and
10% of unreacted starting material 1 was recovered.
Increasing the amount of Ac2O (Table 1, entry 11)
accelerated the reaction, but the formation of sulfone was
also observed. The combination of H2O2, AcOH, and SiO2
in CH2Cl2 (Table 1, entry 12) resulted in 40% yield of 2.
However, a considerable acceleration in the reaction rate
was observed when SiO2 was added (Table 1, entry 13)
to the reaction mixture containing 1, H2O2, and Ac2O in
CH2Cl2. Under these conditions, the reaction was com-
plete within 4 h, and the desired sulfoxide (2) was
obtained in 95% yield.
The scope of the H2O2/Ac2O/SiO2-mediated sulfide to
sulfoxide oxidation was surveyed using additional gly-
cosyl, aliphatic, and aromatic sulfides (Table 2). As
shown in Table 2, good yields (82-95%) of sulfoxides 4,
6, 8, 10, 12, 14, 18, and 20 were obtained from the
corresponding sulfides. The benzylidene protecting group
in sulfide 15 is stable under the acidic reaction conditions
and gave 60% yield of sulfoxide 16 along with 35% of
unreacted starting material. Oxidation of 3, 5, and 7
(Table 2) illustrated that this method was effective for
the oxidation of non-carbohydrate substrates with excel-
a
Reaction conditions: sulfide (1 mmol), 30% H2O2 (1.2 mmol),
lent yields. However, the time required to complete the
Ac2O (1.1 mmol), SiO2 (200 mg, 230-400 mesh) in CH2Cl2 (5 mL)
oxidation of aromatic sulfide (7) was longer than the
at rt. Mixture of R and S isomers. c Isolated yield. Contains
trace quantities of sulfone. e 15% starting sulfide was recovered.
f 35% starting sulfide was recovered.
b
d
aliphatic sulfides 3 and 5. In contrast, the time required
for oxidation of compound 11 and 1 was far less than that
required for the oxidation of compounds 9, 13, 17, and
19. This rate difference indicates that the protecting
group at C-2 of the thioglycoside (ether vs ester) greatly
affected the rate of the sulfide oxidation. Clearly, the
more electron rich the sulfur of the thioglycoside the more
easily it is oxidized.
of sulfoxides or sulfones. This prompted us to investigate
the addition of SiO2 to urea-H2O2 and sulfide 1 (Table
1, entry 5), however, resulted in no improvement in the
yield of sulfoxide 2. Furthermore, oxidation of sulfide 1
using the TBHP/AcOH method9g without SiO2 (Table 1,
entry 6) and with SiO2 (Table 2, entry 7) gave sulfoxide
2 in 20% and 30% yield, respectively. On the basis of
these results, evidently both the urea-H2O2 and TBHP
oxidation methods did not meet our criteria for an
effective glycosyl sulfide to sulfoxide oxidation procedure.
We found that only 200 g of SiO2 adsorbent per mole
(632 g) of substrate (1) was needed to oxidize it to the
sulfoxide 2. This large-scale oxidation gave 2 in 90%
isolated yield at 100% purity producing no detectable
amounts of sulfide or sulfone as determined by HPLC.

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Notes
J . Org. Chem., Vol. 61, No. 23, 1996 8349
Ben zyl p h en yl su lfoxid e (8): white solid13 (95% yield); mp
123-125 °C; Rf 0.1 (1:4 EtOAc/hexane); 1H NMR δ 7.46-7.32
(m, 5H), 7.30-7.20 (m, 3H), 7.00-6.80 (m, 2H), 4.03 (ABq, 2H,
J ) 12.6 Hz, ∆ν ) 27.0 Hz); MS (Fab) 239 (M + Na)+. Anal.
Calcd for C13H12OS: C, 72.20; H, 5.60; S, 14.80. Found: C,
72.41; H, 5.62; S, 14.66.
In conclusion, this oxidation method (H2O2/Ac2O/SiO2
in CH2Cl2) represents a simple, inexpensive, and highly
efficient approach for both small- and large-scale prepa-
ration of glycosyl and noncarbohydrate sulfoxides from
their corresponding sulfides. The sulfoxides 2, 4, 6, 8,
10, 12, 18, and 20 were obtained in pure form by simply
filtering the reaction mixture and washing successively
with aqueous NaHSO3, NaHCO3, and brine followed by
solvent removal. This procedure provides a convenient
and efficient alternative to the standard m-CPBA oxida-
tion of glycosyl sulfides, thus avoiding difficult experi-
mental and workup procedures. We are currently ex-
ploiting this method for the scaleup of other glycosyl
sulfoxides, which will be used in our solution and solid
phase generation of combinatorial libraries. We are also
evaluating the use of our newly developed reagent system
(H2O2/Ac2O/SiO2) in a variety of other oxidations and will
report the results in due course.
Eth ylsu lfen yl 2,3,4,6-tetr a -O-a cetyl-r-D-Ma n n op yr a n o-
sid e (10): white solid (95% yield); mp 134-136 °C; Rf 0.2 (1:2,
1
EtOAc/hexane); IR (KBr) 1746 (br) cm-1; H NMR δ 5.82-5.50
(m, 2H), 5.35-5.20 (m, 1H), 4.63 (s, 1H), 4.40-4.02 (m, 3H),
3.10-2.76 (m, 2H), 2.20-1.94 (m, 12H), 1.42-1.32 (m, 3H); MS
(Fab) 431 (M + Na)+. Anal. Calcd for C16H24O9S: C, 47.05; H,
5.93; S, 7.83. Found: C, 47.16; H, 5.97; S, 7.73.
Eth ylsu lfen yl 2,3,4-tr i-O-ben zyl-r,â-L-fu copyr an oside (12):
1
colorless oil (95% yield); Rf 0.2 (1:2 EtOAc/hexane); H NMR δ
7.45-7.10 (m, 15H), 5.28-4.60 (m, 7H), 4.12-3.47 (m, 5H),
3.24-3.00 (m, 1H), 1.50-1.00 (m, 6H); MS (Fab) 517 (M + Na)+.
Anal. Calcd for C29H34O5S: C, 70.42; H, 6.93; S, 6.47. Found:
C, 70.15; H, 6.87; S, 6.30.
P h en ylsu lfen yl 2-deoxy-2-ph th alim ido-3,4,6-tr i-O-acetyl-
â-D-glu cop yr a n osid e (14). Flash column chromatography of
the crude product over silica gel using gradient eluent (25% to
60% EtOAc in hexane) gave 14 as a white solid (82% yield): mp
Exp er im en ta l Section
78-80 °C; Rf 0.3 (2:1 EtOAc/hexane); IR (KBr) 1749, 1720 cm-1
;
1H NMR δ 7.90-7.47 (m, 7H), 7.24-7.06 (m, 2H), 5.85-5.70 (m,
1H), 5.46 & 5.41 (2d, 1H, J ) 8.4 Hz), 5.16 (t, 0.6H, J ) 10.2
Hz), 5.08 (t, 0.4H, J ) 10.2 Hz), 4.90 (t, 0.6H, J ) 10.2 Hz), 4.67
(t, 0.4H, J ) 10.2 Hz), 4.30-4.05 (m, 2H and solvent -OCH2-
CH3 signal), 3.95 (m, 0.6H), 3.65 (m, 0.4H), 2.20-1.80 (m, 9H);
MS (Fab) 566 (M + Na)+. Anal. Calcd for C26H25NO10S: C,
57.45; H, 4.64; N, 2.58; S, 5.89. Found: C, 57.73; H, 4.55; N,
2.53; S, 5.68.
ACS-grade solvents were used for the reactions. Silica gel
60 (230-400 mesh) was used for flash chromatography. TLC
was performed with 0.2 mm coated commercial silica gel plates
(Kieselgel 60F254). Melting points were determined in open
capillary tubes and are uncorrected. Microanalyses were per-
formed by Atlantic Microlab, Inc., Norcross, GA. All 1H NMR
spectra were recorded at 300 MHz in CDCl3. Mass spectra
(FAB) analyses were performed by Mid-Atlantic spectrometry
services, Frederick, MD. Benzyl phenyl sulfide (7), diisopropyl
sulfide (3), and di-n-butyl sulfide (5) were purchased from
Aldrich Chemical Co. Ethyl 2,3,4,6-tetra-O-acetyl-1-thio-R-D-
mannopyranoside (9) and ethyl 2,3,4-tri-O-benzyl-1-thio-R,â-L-
fucopyranoside (11) were purchased from Toronto Research
Chemicals. All other sulfides (1, 13, 15, 17, and 19) were
synthesized according to the modified literature procedures.12
Gen er a l P r oced u r e for Su lfoxid e Syn th esis fr om Su l-
fid es. To a stirred mixture of appropriate sulfide (1 mmol), Ac2O
(1.1 mmol), and silica gel (200 mg, 230-400 mesh) in CH2Cl2 (5
mL) was added aqueous 30% H2O2 solution (1.2 mmol). After
being stirred at rt between 2 and 24 h (reaction progress is
monitored by TLC), the reaction mixture was filtered through a
fine frit (sintered) funnel and the filtrate washed with saturated
aqueous NaHSO3 (50 mL), NaHCO3 (50 mL), and brine (50 mL).
The organic layer was separated, dried (anhydrous Na2SO4), and
concentrated to furnish a mixture of R and S sulfoxides.
P h en ylsu lfen yl 2,3,4,6-tetr a -O-ben zyl-â-D-glu cop yr a n o-
sid e (2): white solid (95% yield); mp 120-122 °C; Rf 0.3 (1:3
P h en ylsu lfen yl 2-Deoxy-2-a zid o-4,6-O-ben zylid en e-r-D-
glu cop yr a n osid e (16). Flash column chromatography of the
crude product over silica gel using gradient eluent (25%-40%
EtOAc in hexane) gave 16 as white solid (60% yield): mp 151-
153 °C; Rf 0.3 (2:3 EtOAc/hexane). IR (KBr) 3364, 2114 cm-1
;
1H NMR δ 7.76-7.35 (m, 10H), 5.51 (s, 1H), 4.69 (d, 1H, J ) 5.7
Hz), 4.60 (td, 1H, J ) 9.0, 3.3 Hz), 4.16-4.00 (m, 2H), 3.98-
3.88 (m, 1H), 3.64-3.50 (m, 2H), 3.43 (brs, 1H); MS (Fab) 424
(M + Na)+. Anal. Calcd for C19H19N3O5S: C, 56.84; H, 4.77;
N, 10.47; S, 7.97. Found: C, 56.54; H, 4.89; N, 10.31; S, 7.87.
P h en ylsu lfen yl 2,3,4,6-tetr a -O-a cetyl-â-D-glu cop yr a n o-
sid e (18): white solid (95% yield); mp 54-56 °C; Rf 0.2 (1:1
1
EtOAc/hexane); IR (KBr) 1755, 1746 cm-1; H NMR δ 7.65 (m,
2H), 7.54 (m, 3H), 5.38-5.18 (m, 2H), 5.04-4.92 (m, 1H), 4.46
(d, 0.6H, J ) 9.6 Hz), 4.28 (d, 0.4H, J ) 9.6 Hz), 4.20-4.00 (m,
2H), 3.76 & 3.60 (m, 1H), 2.10-1.90 (m, 12H); MS (Fab) 479 (M
+ Na)+. Anal. Calcd for C20H24O10S: C, 52.62; H, 5.30; S, 7.01.
Found: C, 52.43; H, 5.29; S, 6.98.
P h en ylsu lfen yl 2,3,4,6-tetr a -O-p iva loyl-â-D-glu cop yr a n -
osid e (20): white solid (95% yield); mp 63-65 °C; Rf 0.5 (1:3
1
EtOAc/hexane); H NMR δ 7.72-7.14 (m, 25H), 5.04-4.45 (m,
8H), 4.27 (ABq, 1H, J AB ) 12.0 Hz, ∆ν ) 28.1 Hz), 4.14 (d, 0.5H,
J ) 9.9 Hz), 3.98 (d, 0.5H, J ) 9.9 Hz), 3.83-3.72 (m, 2H), 3.62-
3.42 (m, 2H), 3.40-3.28 (m,1H); MS (Fab) 671 (M + Na)+. Anal.
Calcd for C40H40O6S: C, 74.04; H, 6.22; S, 4.93. Found: C, 73.96;
H, 6.30; S, 4.83.
1
EtOAc/hexane); IR (KBr) 1744 (br) cm-1; H NMR δ 7.69-7.43
(m, 5H), 5.35 (t, 1H, J ) 9.0 Hz), 5.06 & 5.01 (2t, 1H, J ) 9.0
Hz), 4.88 (t, 1H, J ) 9.0 Hz), 4.52 (d, 0.65H, J ) 9.9 Hz), 4.26
(d, 0.35H, J ) 9.9 Hz), 4.22-4.11 (m, 1H), 3.99 and 3.89 (m,
1H), 3.74 and 3.60 (m, 1H), 1.25-1.05 (m, 36H); MS (Fab) 647
(M + Na)+. Anal. Calcd for C32H48O10S: C, 61.51; H, 7.75; S,
5.12. Found: C, 61.53; H, 7.79; S, 5.04.
Diisop r op yl su lfoxid e (4): colorless oil13 (95% yield); Rf 0.1
(1:9 EtOAc/hexane); 1H NMR δ 2.81-2.63 (m, 2H), 1.25-1.19
(m, 12H); MS (Fab) 157 (M + Na)+. Anal. Calcd for C6H14OS:
C, 53.70; H, 10.52; S, 23.85. Found: C, 53.67; H, 10.46; S, 23.51.
Di-n -bu tyl su lfoxid e (6): colorless oil13 (95% yield); Rf 0.1
(1:4 EtOAc/hexane); 1H NMR δ 2.67-2.48 (m, 4H), 1.80-1.68
(m, 4H), 1.58-1.38 (m, 4H), 0.95 (t, 6H, J ) 7.2 Hz); MS (Fab)
185 (M + Na)+. Anal. Calcd for C8H18OS: C, 59.22; H, 11.19;
S, 19.72. Found: C, 58.99; H, 11.16; S, 19.34.
Ack n ow led gm en t. We thank Dr. Natan A. Kogan,
Dr. Nigel Allanson, and Ms. Anna Chen of Transcell
Technologies, Inc., for the generous supply of compounds
13, 15, 17, and 19.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
compounds 2, 8, 10, 12, 14, 16, 18, and 20 (8 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
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