Removal of thiazolidinethione auxiliaries with benzyl alcohol mediated by DMAP

Article abstract of DOI:10.1021/jo049204e

In the presence of DMAP, a range of N-acylthiazaolidinethiones carrying different substituents were smoothly converted into the corresponding benzyl esters.

Full text of DOI:10.1021/jo049204e

systematic investigation on the conversion of N-acylthi-
azolidinethiones to the corresponding benzyl esters.
Our main results are outlined in Table 1. All the runs
were carried4 out in CH2Cl2 with DMAP5,6 (4-(dimethyl-
amino)pyridine) as the catalyst. From these data it
appears that the removal of the thiazolidinethione aux-
iliaries is affected mostly by the size of the substituent
at the R-carbon. For those substrates carrying a methyl
group at the R-carbon, the yields were generally high
(entries 1-4, 7, 12, and 13).
Rem ova l of Th ia zolid in eth ion e Au xilia r ies
w ith Ben zyl Alcoh ol Med ia ted by DMAP
Yikang Wu,* Ya-Ping Sun, Yong-Qing Yang, Qi Hu, and
Qi Zhang
State Key Laboratory of Bioorganic & Natural Products
Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Road,
Shanghai 200032, China
A larger substituent at the R-carbon has a negative
effect on the reaction (entries 5, 6, 8, and 9). Similarly,
“branching” of the linear chain also reduced the yield of
the benzyl ester, even if the “branching point” was two
CH2 groups away from the R-carbon (entry 10). If the
branching occurred at a position very close to the
R-carbon, the cleavage of the auxiliary was completely
shut off (entry 17).
yikangwu@mail.sioc.ac.cn
Received May 11, 2004
Abstr a ct: In the presence of DMAP, a range of N-acylthi-
azaolidinethiones carrying different substituents were
smoothly converted into the corresponding benzyl esters.
When the R-substituent is larger than a methyl group,
a delicate effect of changing the substituent on the
auxiliary may also manifest itself (entries 8 and 9). The
less satisfactory result with 13′ compared with that of
13 probably reflected that the Bn group in 13 blocked
the entry of the attacking BnOH more effectively than
the rigid Ph group in 13′.
The effect of the â-substituent did not seem to be as
prominent as that of the R-substituent. However, drasti-
cally increased steric crowding at the carbon â- to the
acyl carbonyl group still may have a discernible influence
on the cleavage reaction. (entry 6 vs 11).
The cleavage of 23 was exceptionally difficult (yielding
benzyl isovalerate along with other unidentified side-
products). However, it was possible to enlarge the rate
difference between the desired cleavage and the side-
reaction(s) and thus improve the yield of 24 through
careful “tuning” of the experimental conditions (entry 14).
It is interesting to note that if the acyl group on the
â-hydroxyl group was removed (i.e., 25) essentially no
desired benzyl ester was formed (entry 15). Some uni-
dentified side-products (of relative high polarity and
showing strong fluorescence under 254 nm UV light)
were generated instead. With an allyl group to replace
the TES (entry 16), the situation was improved slightly.
The effect of the quantity of DMAP utilized in the
reaction is not always straightforward. For most sub-
strates examined in this work only a catalytic amount of
DMAP was sufficient. Slight variation7 in the amount of
the added DMAP only led to changes in the reaction rate,
but not the yield. However, a so far unexplainable
Chiral 4-monosubstituted thiazolidinethiones derived
from inexpensive/readily available amino acids are use-
ful1 auxiliaries in asymmetric synthesis. Compared with
their oxazolidinone and oxazolidinethione counterparts,
removal of the these auxiliaries from the N-acylthiazo-
lidinthiones after completion of the chiral induction is
generally easier.1a,b Such a feature has great merits in
the synthesis of complicated “fragile” molecules contain-
ing many different functionalities.
However, removal of the 4-monosubstituted thiazoli-
dinethione auxiliaries is not always as trouble-free as one
might deduce from the examples1a,b,f,h,i in the literature.
With increasing the steric crowding around the N-acyl
group, removal of the auxiliary becomes increasingly
difficult. The cleavage2 can be even further complicated
when the N-acylthiazolidinethione contains a â-hydroxyl
group. An additional factor that still further reduces the
number of potential choices is that the sulfur-containing
auxiliaries are readily oxidized and thus destroyed under
Evans’ H2O2/LiOH3 conditions. Thus, it appears that new
mild/efficient methods for converting N-acylthiazolidine-
thiones to corresponding esters or carboxylic acids are
still in great need. Here in this Note we report the first
(1) See, e.g.: (a) Crmmins, M. T.; King, B. W.; Tabet, E. A.;
Chaudhary, K. J . Org. Chem. 2001, 66, 894-902. (b) Crimmins, M.
T.; Chaudhary, K. Org. Lett. 2000, 2, 775-778. (c) Evans, D. A.;
Downey, C. W.; Shaw, J . T.; Tedrow, J . S. Org. Lett. 2002, 4, 1127-
1130. (d) Wu, Y.-K.; Shen, X.; Tang, C.-J .; Chen, Z.-L.; Hu, Q.; Shi, W.
J . Org. Chem. 2002, 6, 3802-3810. (e) Wu, Y.-K.; Shen, X.; Yang, Y.-
Q.; Hu, Q.; Huang, J .-H. Tetrahedron Lett. 2004, 45, 199-202. (f) Cosp,
A.; Romea, P.; Talavera, P.; Urpi, F.; Vilarrasa, J .; Font-Bardia, M.;
Solans, X. Org. Lett. 2001, 3, 615-618. (g) Hart, D. J .; Patterson, S.;
Unch, J . P.; Synlett 2003, 1334-1338. (h) Cosp, A.; Larrosa, I.; Vilasis,
I.; Romea, P.; Urpi, F.; Vilarrasa, J . Synlett 2003, 1109-1112. (i)
Larrosa, I.; Romea, P.; Urpi, F.; Balsells, D.; Vilarrasa, J .; Font-Bardia,
M.; Solans, X. Org. Lett. 2002, 4, 4651-4654. (j) Ambhaikar, N. B.;
Snyder, J . P.; Liotta, D. C. J . Am. Chem. Soc. 2003, 125, 3690-3691.
(k) Crimmins, M. T.; McDougall, P. J . Org. Lett. 2003, 5, 591-594. (l)
Efremov, I.; Paqutte, L. A. J . Am. Chem. Soc. 2000, 122, 9324-9325.
(m) Zhang, Y.-C.; Phillips, A. J .; Sammakia, T. Org. Lett. 2004, 6,
23-25.
(4) Because most of the runs were performed in the winter, the
ambient temperature was low and varied considerably. The results
appeared to be similar at 20 °C (entry 1).
(5) Su, D.-W.; Wang, Y.-C.; Yan, T.-H. Tetrahedron Lett. 1999, 40,
4197-4198.
(6) Yan’s procedure (ref 5) has been recently applied to the removal
of 4-isopropyl-thiazolidinethione by the Romea-Urpi group (see refs
1f, 1h, and 1i, where the conversion of the acyl-thiazolidinethiones to
methyl/ethyl esters was only very briefly mentioned).
(7) For some substrates, stoichiometric amounts of DMAP must be
utilized in order to obtained the desired benzyl esters in synthetically
useful yields (entries 12-14). Using significantly smaller amounts of
DMAP in these cases resulted in very sluggish cleavage and extensive
side-reactions.
(2) In this paper, cleavage refers only to those conversions of
auxiliary acyl compounds into the corresponding esters or carboxylic
acids. Reductive cleavage is not included.
(3) Evans, D. A.; Britton, T. C.; Ellman, J . A. Tetrahedron Lett. 1987,
28, 6141-6144.
10.1021/jo049204e CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/10/2004
J . Org. Chem. 2004, 69, 6141-6144
6141

TABLE 1. Con ver sion of Va r iou s
N-Acylth ia zolid in eth ion es to Cor r esp on d in g Ben zyl
Ester s
exception was also observed. When we treated 13 with
0.2 equiv of DMAP (instead of 0.1 equiv as in entry 8),
the benzyl ester 14 was formed in only 26% yield. Most
of the 13 was converted to other unidentified side-
products.
It should be noted that in those successful runs, the
free auxiliary could be recovered in high yields. From
entry 1, for instance, (R)-4-benzyl-thiazolidinethione was
recovered essentially quantitatively.
For the purpose of comparison, we also briefly exam-
ined a few other catalysts/conditions: K2CO3/MeOH,
which worked very well8 (affording corresponding methyl
esters) for some other N-acylthiazolidinethiones that did
not contain a â-hydroxyl group, led to extensive formation
of side-products within 1 h. Imidazole/MeOH1a,b was inert
on those hindered substrates. 2,6-Lutidine/BnOH was
also completely inactive in such cleavage reactions. DBU
behaved similar to DMAP. However, the reactions were
not as clean as those using DMAP. With water to replace
the benzyl alcohol, it was possible to cleave9 the nonhin-
dered N-acylthiazolidinethiones in good yields as exem-
plified by entry 18. However, the reaction completely
failed for those hindered substrates.
Exp er im en ta l Section
All the substrates were prepared by TiCl4-mediated asym-
metric aldolization as reported by Crimmins1a,b and co-workers.
The TBS or TES protection of the â-hydroxyl group in the
Crimmins aldols was realized by treatment with TBSCl or
TESCl in the presence of 2,6-lutidine. Acylation of the â-hydroxyl
group (23) was achieved with the corresponding acid chloride
in pyridine under the standard acylation conditions. All 1H NMR
spectra were recorded in CDCl3 (with Me4Si as the internal
reference) on NMR spectrometers operating at 300 MHz.
Gen er a l P r oced u r e. A solution (ca. 0.2 M for the substrate)
of the substrate, BnOH, and DMAP in CH2Cl2 was stirred at
the ambient temperature. The reaction was monitored by TLC.
When the reaction was complete, the mixture was diluted with
ether, washed with 1 N HCl, water, and brine, and dried over
anhydrous Na2SO4. The crude residue after removal of the
solvents was chromatographed on silica gel (eluting with a
mixture of EtOAc/hexanes of proper ratio) to afford the pure
product.
Da ta for Com p ou n d 1. A colorless oil: [R]20 +119.8 (c 5.0,
D
CHCl3). 1H NMR δ 7.38-7.26 (m, 5H), 5.35 (ddd, J ) 4.2, 6.7,
10.6 Hz, 1H), 4.48 (dq, J ) 2.9, 6.9 Hz, 1H), 3.96-3.90 (m,
1H), 3.40 (dd, J ) 7.3 Hz, 1H), 3.22 (dd, J ) 4.0, 13.2 Hz, 1H),
3.04 (dd, J ) 10.6, 13.3 Hz, 1H), 2.91 (d, J ) 11.5 Hz, 1H), 2.67
(d, J ) 3.3 Hz, 1H), 1.59-1.28 (m, 8H), 1.25 (d, J ) 6.9 Hz, 3H),
0.89 (t, J ) 6.8 Hz, 3H). FT-IR (film) 3447, 1694, 1455, 1164,
702 cm-1. EI-MS m/z (%) 365 (M+, 2.1), 332 (20.1), 314 (3.7),
276 (15.8), 20 (100), 118 (87.5), 91 (58.2). EI-HRMS cald for
C
19H28NO2S2 (M+ + 1) 366.1556; found 366.1584.
Da ta for Com p ou n d 1′. A colorless oil: [R]27D +162.1 (c 0.50,
CHCl3). 1H NMR δ 5.18 (ddd, J ) 1.3, 6.6, 7.7 Hz, 1H), 4.47 (dq,
J ) 2.7, 7.1 Hz, 1H), 3.92-3.88 (m, 1H), 3.51 (dd, J ) 7.9, 11.9
Hz, 1H), 3.04 (dd, J ) 1.3, 12.0 Hz, 1H), 2.96 (d, J ) 2.6 Hz,
1H), 2.34 (dt, J ) 20.5, 6.7 Hz, 1H), 1.52-1.20 (m, 8H), 1.26 (d,
J ) 6.6 Hz, 3H), 1.06 (d, J ) 6.8 Hz, 3H), 0.97 (d, J ) 6.7 Hz,
3H), 0.88 (t, J ) 6.5 Hz, 3H). FT-IR (film) 3446, 1694, 1466,
1160 cm-1. ESI-MS m/z 318 ([M + 1]+). ESI-HRMS calcd for
a
Similar result (94%) was also obtained at 20 °C, with the
C
15H27NO2S2Na ([M + Na]+) 340.1375; found 340.1390.
b
auxiliary quantitatively recovered. Another 0.1 equiv of DMAP
was added after 9 h. c About 23% unreacted 17 was recovered.
Several unidentified compounds were obtained. e Along with
d
(8) See, e.g.: (a) Yamada, S.; Misono, T.; Ichikawa, M.; Morita, C.
Tetrahedron 2001, 57, 8939-8950. (b) Nagao, Y.; Hagiwara, Y.; Tohjo,
T.; Hasegawa, Y.; Ochiai, M. J . Org. Chem. 1988, 53, 5983-5986.
(9) Similar results were obtained using THF as the solvent. It is
interesting to note that the reaction in CH2Cl2 seemed to be faster,
although water is not soluble in this solvent.
several so far unidentified, more polar side-products (with strong
fluorescence under 254 nm UV light), which were almost insepa-
g
rable from each other. f Most of the 29 remained unreacted. In
this run, 2.0 equiv of water was utilized in place of the BnOH.
6142 J . Org. Chem., Vol. 69, No. 18, 2004

Da ta for Com p ou n d 2. A colorless oil: [R]19 +11.1 (c 0.4,
5.6 Hz, 1H), 5.26 (br d, J ) 17 Hz, 1H), 5.17 (br d, J ) 10.7 Hz,
1H), 5.15 (s, 2H), 3.96-3.94 (m, 2H), 3.81-3.77 (m, 1H), 3.41 (t,
J ) 5.8 Hz, 2H), 2.48 (dt, J ) 10.4, 4.5 Hz, 1H), 2.43 (d, J )
4.3 Hz, 1H, OH), 1.69-1.23 (m, 16H), 0.86 (t, J ) 5.6 Hz, 3H).
FT-IR (film) 3445, 1732, 1456, 1157, 1107, 698 cm-1. EI-MS m/z
(%) 317 (M+ - 59, 0.6), 263 (2.3), 211 (6.2), 143 (18.0), 91 (100).
ESI-HRMS calcd for C23H36O4Na ([M + Na]+) 399.2506; found
399.2520.
Da ta for Com p ou n d 11. A colorless oil: [R]25D +70.0 (c 0.45,
CHCl3). 1H NMR δ 7.37-7.26 (m, 5H), 5.34 (ddd, J ) 3.6, 6.5,
10.5 Hz, 1H), 4.50 (s, 2H), 4.50-4.43 (m, 1H), 3.95-3.92 (m, 1H),
3.48 (t, J ) 6.3 Hz, 2H), 3.39 (dd, J ) 7.2, 11.4 Hz, 1H), 3.21
(dd, J ) 13.4, 3.6 Hz, 1H), 3.04 (dd, J ) 10.2, 12.8 Hz, 1H),
2.86 (d, J ) 6.7 Hz, 1H), 2.76-2.72 (br s, 1H, OH), 1.65-1.38
(m, 6H), 1.24 (d, J ) 7.0 Hz, 3H). FT-IR (film) 3445, 1694,
1602, 1495, 1164, 742, 700 cm-1. ESI-MS m/z 480.30 ([M + Na]+).
EI-HRMS cald for C25H31NO3S2Na ([M + Na]+) 480.1638; found
480.1665.
Da ta for Com p ou n d 12. A colorless oil: [R]25D -2.08 (c 0.45,
CHCl3). 1H NMR δ 7.39-7.26 (m, 5H), 5.15 (s, 2H), 4.51 (s, 2H),
3.93-3.89 (m, 1H), 3.49 (t, J ) 6.2 Hz, 1H), 2.97 (br d, J ) 4.1
Hz, 1H, OH), 2.58 (dq, J ) 4.1, 7.3 Hz, 1H), 1.79-1.48 (m, 6H),
1.21 (d, J ) 6.9 Hz, 3H). FT-IR (film) 3450, 1731, 1601, 1497,
1455, 1101, 737, 698 cm-1. ESI-MS m/z 357.20 ([M + 1]+), 379.25
([M + Na]+). ESI-HRMS calcd for C22H28O4Na ([M + Na]+)
379.1880; found 379.1898.
Da ta for Com p ou n d 13. A colorless oil: [R]24D +61.0 (c 0.35,
CHCl3). 1H NMR δ 7.42-7.27 (m, 5H), 6.27 (br d, J ) 8.2 Hz,
1H), 5.02 (dt, J ) 8.7, 4.3 Hz, 1H), 3.95-3.88 (m, 1H), 3.92 (dd,
J ) 8.3, 11.2 Hz, 1H), 3.05 (dd, J ) 1.6, 11.2 Hz, 1H), 2.23 (br
d, J ) 3.6 Hz, 1H, OH), 1.82-1.05 (m, 58H), 0.86 (t, J ) 6.7 Hz,
6H). FT-IR (film) 3447, 1700, 1465, 1155, 697 cm-1. EI-MS m/z
(%) 507 (M+ - 195, 3.1), 488 (4.7), 462 (8.8), 195 (100), 135 (86.4).
ESI-HRMS calcd for C43H75NO2S2Na ([M + Na]+) 724.5131;
found 724.5148.
D
CHCl3). 1H NMR δ 7.38-7.26 (m, 5H), 5.14 (s, 2H), 3.93-3.89
(m, 1H), 2.58 (dq, J ) 3.5, 7.1 Hz, 1H), 2.46 (d, J ) 4.7,
1H, OH), 1.48-1.27 (m, 8H), 1.20 (d, J ) 7.1 Hz, 3H), 0.88
(t, J ) 6.8 Hz, 3H). FT-IR (film) 3449, 1731, 1456, 1171, 698
cm-1. ESI-MS m/z 265.25 ([M + 1]+). ESI-HRMS calcd for
C
16H24O3Na ([M + Na]+) 287.1618; found 287.1628.
Da ta for Com p ou n d 3. A colorless oil: [R]25D +129.4 (c 0.65,
CHCl3). 1H NMR δ 7.38-7.26 (m, 5H), 5.28 (ddt, J ) 10.0, 16.8,
6.9 Hz, 1H), 5.36 (ddd, J ) 3.5, 6.9, 10.5 Hz, 1H), 5.05 (br d, J
) 16.8 Hz, 1H), 4.98 (br d, J ) 10.1 Hz, 1H), 4.47 (dq, J ) 3.3,
6.8 Hz, 1H), 3.95 (br dt, J ) 11.5, 3.1 Hz, 1H), 3.40 (dd, J ) 7.2,
10.5 Hz, 1H), 3.21 (dd, J ) 3.7, 13.2 Hz, 1H), 3.04 (dd, J ) 10.7,
13.3 Hz, 1H), 2.90 (d, J ) 11.5 Hz, 1H), 2.76 (d, J ) 3.3 Hz, 1H),
2.29-2.07 (m, 2H), 1.67-1.62 (m, 1H), 1.27-1.21 (m, 1H), 1.22
(d, J ) 6.5 Hz, 3H). FT-IR (film) 3530, 1691, 1265, 910 cm-1
.
EI-MS m/z (%) 349 (M+ + 1, 3.3), 331 (2.2), 316 (23.8), 210 (100),
118 (62.3), 91 (42.7). ESI-HRMS calcd for C18H23NO2S2Na ([M
+ Na]+) 372.1062; found 372.1088.
Da ta for Com p ou n d 4. A colorless oil: [R]24 +3.83 (c 1.4,
D
CHCl3). 1H NMR δ 7.41-7.34 (m, 5H), 5.82 (ddt, J ) 10.5, 17.4,
6.5 Hz, 1H), 5.16 (s, 2H), 5.16-4.97 (m, 2H), 3.98 (dt, J ) 3.8,
9.1 Hz, 1H), 2.60 (dq, J ) 3.8, 7.2 Hz, 1H), 2.49 (br s, 1H, OH),
2.35-2.05 (m, 2H), 1.61-1.44 (m, 2H), 1.22 (d, J ) 7.1 Hz, 3H).
FT-IR (film) 3495, 1732, 1640, 1456, 1173 cm-1. ESI-MS m/z
249.1 ([M + 1]+). ESI-HRMS calcd for C15H20O3Na ([M + Na]+)
271.1305; found 271.1318.
Da ta for Com p ou n d 5. A colorless oil: [R]27D +116.1 (c 0.75,
CHCl3). 1H NMR δ 7.57-7.26 (m, 5H), 6.64 (d, J ) 15.7 Hz, 1H),
6.20 (dd, J ) 5.8, 15.6 Hz, 1H), 5.23 (ddd, J ) 3.4, 6.3, 10.3 Hz,
1H), 4.80-4.56 (m, 2H), 3.23 (dd, J ) 3.4, 10.3 Hz, 1H), 3.19
(dd, J ) 6.6, 11.3 Hz, 1H), 3.03 (dd, J ) 10.9, 13.5 Hz, 1H),
2.82 (d, J ) 11.5 Hz, 1H), 2.67 (br s, 1H, OH), 1.32 (d, J ) 6.3
Hz, 3H). FT-IR (film) 3445, 1698, 1601, 1495, 1342, 1137 cm-1
.
EI-MS m/z (%) 364 (M+ - 33, 15.7), 265 (10.2), 210 (42.7), 160
Da ta for Com p ou n d 13′. A colorless oil: [R]27D +39.0 (c 0.95,
CHCl3). 1H NMR δ 7.37-7.26 (m, 5H), 5.39 (ddd, J ) 3.4, 6.6,
10.6 Hz, 1H), 5.00 (dt, J ) 9.7, 4.0 Hz, 1H), 3.92-3.81 (m, 1H),
3.36 (dd, J ) 7.2, 11.8 Hz, 1H), 3.23 (dd, J ) 3.6, 13.0 Hz, 1H),
3.05 (dd, J ) 10.9, 13.2 Hz, 1H), 2.86 (d, J ) 11.1 Hz, 1H),
2.15 (br s, 1H, OH), 1.95-1.80 (m, 1H), 1.80-1.00 (m, 57H),
0.88 (t, J ) 6.5 Hz, 6H). FT-IR (film) 3505, 1702, 1466, 1190,
703 cm-1. ESI-MS m/z 716.8 ([M + 1]+). ESI-HRMS calcd for
(33.2), 131 (36.2), 118 (93.6), 91 (100). ESI-HRMS calcd for
C
22H23NO2S2Na ([M + Na]+) 420.1062; found 420.1094.
Da ta for Com p ou n d 6. A colorless oil: [R]27 +4.75 (c 0.30,
D
CHCl3). 1H NMR δ 7.60-7.26 (m, 5H), 6.64 (d, J ) 16.0 Hz, 1H),
6.17 (dd, J ) 6.2, 16.1 Hz, 1H), 5.16 (s, 2H), 4.60-4.58 (m, 1H),
2.76 (dq, J ) 4.7, 7.1 Hz, 1H), 2.69 (br s, 1H, OH), 1.20 (d, J )
6.7 Hz, 3H). FT-IR (film) 3462, 1731, 1600, 1496, 1455, 1137,
749, 695 cm-1. EI-MS m/z (%) 296 (M+, 0.5), 205 (16.7), 187 (5.4),
180 (10.8), 133 (35.1), 131 (34.9), 115 (12.7), 91 (100). ESI-HRMS
calcd for C19H20O3Na ([M + Na]+) 319.1305; found 319.1333.
Da ta for Com p ou n d 7. A colorless oil: [R]24D +115.3 (c 0.20,
C
44H77NO2S2Na ([M + Na]+) 738.5288; found 738.5266.
Da ta for Com p ou n d 14. A white crystal: mp 70-71 °C.
[R]18D -5.01 (c 0.65, CHCl3). 1H NMR δ 7.38-7.25 (m, 5H), 5.15
(s, 2H), 3.72-3.85 (m, 1H), 2.47 (dt, J ) 10.2, 4.7 Hz, 1H),
2.33 (br d, J ) 4.5 Hz, 1H, OH), 1.69-1.19 (m, 58H), 0.88 (d, J
) 6.6 Hz, 3H). FT-IR (film) 3444, 1727, 1469, 1456, 1157, 698
cm-1. ESI-MS m/z 637.70 ([M + Na]+). ESI-HRMS calcd for
1
CHCl3). H NMR δ 7.42-7.27 (m, 5H), 6.26 (d, J ) 8.4 Hz, 1H),
5.76 (ddt, J ) 17.6, 10.0, 6.7 Hz, 1H), 5.07-4.99 (m, 1H), 4.96
(br d, J ) 17.0 Hz, 1H), 4.92 (br d, J ) 10.1 Hz, 1H), 4.06 (t, J
) 6.4 Hz, 2H), 3.97-3.90 (m, 2H), 3.07 (dd, J ) 1.5, 11.4 Hz,
1H), 2.55 (br quint, J ) 7.5 Hz, 1H), 2.45-2.36 (m, 2H), 1.19
(s, 9H). FT-IR (film) 3490, 1723, 1641, 1480, 1137, 698
cm-1. ESI-MS m/z 464.2 ([M + Na]+). ESI-HRMS calcd for
C
41H74O3Na ([M + Na]+) 637.5530; found 637.5552.
Da ta for Com p ou n d 15. A colorless oil: [R]27D +66.1 (c 1.95,
1
CHCl3). H NMR δ 7.38-7.25 (m, 10H), 5.34 (ddd, J ) 4.2, 7.0,
10.7 Hz, 1H), 4.91 (dt, J ) 8.0, 4.0 Hz, 1H), 4.50 (s, 2H), 3.96-
3.87 (m, 1H), 3.48 (t, J ) 6.3 Hz, 2H), 3.43-3.22 (m, 6H), 3.06
(dd, J ) 10.6, 12.9 Hz, 1H), 2.52 (d, J ) 11.7 Hz, 1H), 2.25 (br
d, J ) 3.5 Hz, 1H, OH), 2.20-1.80 (m, 4H), 1.78 (s, 3H), 1.86-
1.42 (m, 6H). FT-IR (film) 3442, 1694, 1602, 1495, 1162, 700
cm-1. EI-MS m/z (%) 556 (M+ - 33, 1.0), 480 (0.9), 209 (20.0),
119 (68.5), 91 (100). ESI-HRMS calcd for C30H39NO3S4Na ([M
+ Na]+) 612.1710; found 612.1704.
C
24H33NO4S2Na ([M + Na]+) 486.1743; found 486.1766.
Da ta for Com p ou n d 8. A colorless oil: [R]27 +7.69 (c 0.50,
D
CHCl3). 1H NMR δ 7.38-7.33 (m, 5H), 5.78 (ddt, J ) 17.3, 10.1,
7.0 Hz, 1H), 5.14 (s, 2H), 5.06 (br d, J ) 17.0 Hz, 1H), 5.00 (br
d, J ) 10.0 Hz, 1H), 4.03 (t, J ) 6.5 Hz, 2H), 3.89-3.80 (m, 1H),
2.60 (dt, J ) 5.3, 8.7 Hz, 1H), 2.46-2.34 (m, 2H), 1.17 (s, 9H).
FT-IR (film) 3514, 1727, 1642, 1480, 1158, 698 cm-1. ESI-MS
m/z 377.2 ([M + H]+). ESI-HRMS calcd for C22H32O5Na ([M +
Na]+) 399.2142; found 399.2152.
Da ta for Com p ou n d 16. A colorless oil: [R]24 +1.81 (c 1.4,
D
Da ta for Com p ou n d 9. A colorless oil: [R]27 -99.2 (c 0.85,
CHCl3). 1H NMR δ 7.41-7.28 (m, 10H), 5.18 (s, 2H), 452 (s, 2H),
3.92-3.83 (m, 1H), 3.48 (t, J ) 6.0 Hz, 2H), 3.39-3.24 (m, 4H),
2.51-2.47 (m, 1H), 2.11-1.13 (m, 10H), 1.73 (s, 3H). FT-IR
(film) 3448, 1727, 1465, 1365, 1101, 735, 697 cm-1. ESI-MS m/z
489.3 ([M + 1]+), 511.2 ([M + Na]+). ESI-HRMS calcd for
D
CHCl3). 1H NMR δ 7.41-7.26 (m, 5H), 6.26 (dd, J ) 1.2, 8.1 Hz,
1H), 5.92 (ddt, J ) 17.1, 10.5, 5.7 Hz, 1H), 5.28 (br d, J ) 17
Hz, 1H), 5.17 (br d, J ) 10.5 Hz, 1H), 5.02 (dt, J ) 9.1, 4.0 Hz,
1H), 3.98-3.88 (m, 4H), 3.44 (t, J ) 6.2 Hz, 2H), 3.05 (dd, J )
1.7, 11.4 Hz, 1H), 2.31 (br s, 1H, OH), 1.89-1.38 (m, 8H), 1.25-
1.08 (m, 8H), 0.85 (t, J ) 6.8 Hz, 3H). FT-IR (film) 3440, 1699,
1600, 1496, 1158, 698 cm-1. EI-MS m/z (%) 430 (M+ - 33, 4.1),
404 (8.7), 234 (8.5), 209 (17.0), 196 (48.1), 41 (100). ESI-HRMS
calcd for C25H37NO3S2Na ([M + Na]+) 486.2107; found 486.2129.
Da ta for Com p ou n d 10. A colorless oil: [R]25D -48.9 (c 1.00,
CHCl3). 1H NMR δ 7.42-7.25 (m, 5H), 5.91 (ddt, J ) 17.3, 10.3,
C
27H36O4S2Na ([M + Na]+) 511.1947; found 511.1939.
Da ta for Com p ou n d 17. A colorless oil: [R]25D -94.0 (c 1.00,
1
CHCl3). H NMR δ 7.41-7.26 (m, 5H), 6.26 (d, J ) 8.5 Hz, 1H),
5.03 (dt, J ) 8.7, 4.5 Hz, 1H), 4.36-4.22 (m, 1H), 3.94 (dd, J )
10.2, 8.9 Hz, 1H), 3.52 (br s, 1H), 3.05 (d, J ) 11.2 Hz, 1H),
3.07-2.92 (m, 2H), 2.78-2.73 (m, 2H), 2.40 (dd, J ) 9.2, 15.1
Hz, 1H), 2.04-1.80 (m, 5H), 1.75-1.18 (m, 15H), 0.91 (t, J )
J . Org. Chem, Vol. 69, No. 18, 2004 6143

6.8 Hz, 3H), 0.85 (t, J ) 6.7 Hz, 3H). FT-IR (film) 3444, 1699,
1602, 1495, 1158, 756, 698 cm-1. EI-MS m/z (%) 537 (M+ - 16,
5.2), 430 (5.7), 358 (10.5), 287 (23.8), 195 (42.5), 189 (100), 135
(51.1). EI-HRMS cald for C28H43NO2S4Na ([M + Na]+) 576.2069;
found 576.2035.
1164, 746 cm-1. ESI-MS m/z 501.3 ([M + Na]+), 479.2 ([M +
1]+). ESI-HRMS calcd for C27H46O5SiNa ([M + Na]+) 501.3007;
found 501.3030.
Da ta for Com p ou n d 25. A colorless oil: [R]29D -166.7 (c 1.03,
1
CHCl3). H NMR δ 7.42-7.25 (m, 5H), 6.28 (d, J ) 7.8 Hz, 1H),
Da ta for Com p ou n d 18. A colorless oil: [R]24D -18.9 (c 0.35,
CHCl3). 1H NMR δ 7.39-7.26 (m, 5H), 5.16 (s, 2H), 4.09 (br t, J
) 7.2 Hz, 1H), 3.76 (d, J ) 2.9 Hz, 1H, OH), 3.01-2.82 (m, 2H),
2.80-2.68 (m, 2H), 2.54 (q, J ) 7.0 Hz, 1H), 2.35 (dd, J ) 9.4,
15.1 Hz, 1), 2.05-1.68 (m, 6H), 1.60-1.18 (m, 14H), 0.89 (t, J )
7.5 Hz, 3H), 0.85 (t, J ) 7.4 Hz, 3H). FT-IR (film) 3431, 1731,
1456, 1158, 697 cm-1. EI-MS m/z 467.3 ([M + 1]+). EI-HRMS
cald for C26H42O3S2Na ([M + Na]+) 489.2468; found 489.2462.
Da ta for Com p ou n d 19. A colorless oil: [R]25D +76.7 (c 0.40,
CHCl3). 1H NMR δ 7.33-7.22 (m, 5H), 5.14 (ddd, J ) 3.9, 6.7,
10.4 Hz, 1H), 4.52 (dt, J ) 12.1, 6.6 Hz, 1H), 3.96 (dd, J ) 5.2,
10.6 Hz, 1H), 3.35-3.23 (m, 2H), 2.99 (dd, J ) 10.9, 13.1 Hz,
1H), 2.84 (d, J ) 11.1 Hz, 1H), 1.52-1.15 (m, 8H), 1.09 (d, J )
6.8 Hz, 3H), 0.83 (s, 9H), 0.83 (t, J ) 7.3 Hz, 3H), 0.00 (s, 6H).
FT-IR (film) 1699, 1456, 1163, 836, 775, 702 cm-1. ESI-MS m/z
480.2 ([M + 1]+). ESI-HRMS calcd for C25H41NO2S2SiNa ([M +
Na]+) 502.2240; found 502.2254.
5.03 (dt, J ) 7.7, 5.7 Hz, 1H), 3.92 (dd, J ) 8.3, 11.2 Hz, 1H),
3.83 (br quint, J ) 6.0 Hz, 1H), 3.74 (br ddd, J ) 5.4, 5.4, 2.9
Hz, 1H), 3.06 (dd, J ) 1.8, 11.2 Hz, 1H), 2.60 (d, J ) 2.5 Hz, 1H,
OH), 1.83-1.72 (m, 2H), 1.21-1.16 (m, 4H), 1.18 (d, J ) 5.9 Hz,
3H), 0.97 (t, J ) 7.9 Hz, 9H), 0.77 (t, J ) 6.7 Hz, 3H), 0.62 (br
q, J ) 8.0 Hz, 6H). FT-IR (film) 3519, 1698, 1456, 1162, 744,
697 cm-1. ESI-MS m/z: 482.4 ([M + 1]+). ESI-HRMS calcd for
C24H39NO3S2SiNa ([M + Na]+) 504.2033; found 504.2019.
Da ta for Com p ou n d 27. A colorless oil: [R]19D -123.7 (c 1.07,
CHCl3). 1H NMR δ 7.41-7.27 (m, 5H), 6.28 (br d, J ) 7.7 Hz,
1H), 5.91 (ddt, J ) 10.7, 17.3, 5.0 Hz, 1H), 5.30 (dd, J ) 17.3,
1.7 Hz, 1H), 5.19 (dd, J ) 1.8, 10.6 Hz, 1H), 5.13 (q, J ) 6.3 Hz,
1H), 4.08 (br dd, J ) 12.7, 5.3 Hz, 1H), 3.97-3.84 (m, 3H), 3.45
(quint, J ) 6.2 Hz, 1H), 3.04 (dd, J ) 11.2, 1.6 Hz, 1H), 2.40 (br
d, J ) 3.7 Hz, 1H, OH), 1.21 (d, J ) 5.9 Hz, 3H), 1.20-1.13 (m,
4H), 0.77 (t, J ) 6.5 Hz, 3H). FT-IR (film) 3469, 1694, 1495,
1455, 1152, 1045, 698 cm-1. ESI-MS m/z: 430 ([M + Na]+). ESI-
HRMS calcd for C21H29NO3NaS2Na ([M + Na]+) 430.1481; found
430.1480.
Da ta for Com p ou n d 28. A colorless oil: [R]27D +2.65 (c 0.35,
CHCl3). 1H NMR δ 7.38-7.26 (m, 5H), 5.85 (ddt, J ) 17.8, 11.2,
5.8 Hz, 1H), 5.24 (br d, J ) 17.4 Hz, 1H), 5.14 (br d, J ) 11 Hz,
1H), 5.13 (s, 2H), 3.98 (qt, J ) 1.7, 6.0 Hz, 1H), 3.90-3.83 (m,
2H), 3.31 (dt, J ) 11.0, 6.3 Hz, 1H), 2.57 (ddd, J ) 3.7, 7.3, 10.4
Hz, 1H), 2.46 (d, J ) 2.5 Hz, 1H), 1.83-1.60 (m, 4H), 1.14 (d, J
) 5.7 Hz, 3H), 0.85 (t, J ) 7.0 Hz, 3H). FT-IR (film) 3440, 1732,
1456, 1249, 697 cm-1. EI-MS m/z (%) 263 (M+ - 57, 0.1), 235
(9.0), 91 (100). ESI-HRMS calcd for C19H28O4Na ([M + Na]+)
343.1880; found 343.1894.
Da ta for Com p ou n d 20. A colorless oil: [R]27D +9.83 (c 0.35,
CHCl3). 1H NMR δ 7.34-7.29 (m, 5H), 5.11 (d, J ) 12.5 Hz, 1H),
5.03 (d, J ) 12.5 Hz, 1H), 3.98 (dd, J ) 5.5, 11.2 Hz, 1H), 3.35-
3.23 (m, 2H), 2.56 (dq, J ) 2.1, 7.2 Hz, 1H), 1.46-1.21 (m, 7H),
1.16 (d, J ) 7.4 Hz, 3H), 0.95-0.70 (m, 1H), 0.84 (s, 9H), 0.00
(s, 6H). FT-IR (film) 1733, 1462, 1255, 836, 775, 697 cm-1. ESI-
MS m/z 379.3 ([M + 1]+). ESI-HRMS calcd for C22H38O3SiNa
([M + Na]+) 401.2482; found 401.2499.
Da ta for Com p ou n d 21. A colorless oil: [R]27D +103.3 (c 0.50,
CHCl3). 1H NMR δ 4.99 (t, J ) 6.6 Hz, 1H), 4.51 (dt, J ) 13.1,
6.6 Hz, 1H), 3.99 (dd, J ) 5.3, 10.8 Hz, 1H), 3.45 (dd, J ) 7.9,
11.6 Hz, 1H), 3.04 (d, J ) 11.3 Hz, 1H), 2.41 (dt, J ) 20.4, 6.7
Hz, 1H), 1.49-1.25 (m, 8H), 1.22 (d, J ) 6.6 Hz, 3H), 1.07 (d, J
) 6.8 Hz, 3H), 0.97 (d, J ) 8.0 Hz, 3H), 0.96 (t, J ) 8.0 Hz, 9H),
0.59 (q, J ) 7.6 Hz, 6H). FT-IR (film) 1694, 1465, 740 cm-1. ESI-
MS m/z 432.2 ([M + 1]+). MALDI-HRMS calcd for C21H41NO2S2-
Si ([M + 1]+) 432.2421; found 432.2429.
Da ta for Com p ou n d 29. A colorless oil: [R]24D -94.7 (c 0.60,
CHCl3). 1H NMR δ 7.38-7.26 (m, 5H), 6.31 (br d, J ) 8.4 Hz,
2H), 5.23 (dd, J ) 5.5, 8.7 Hz, 1H), 4.03-3.98 (m, 1H), 3.91 (dd,
J ) 8.4, 11.2 Hz, 1H), 2.16-2.09 (br m, 2H), 1.60-1.19 (m, 8H),
1.06 (d, J ) 6.6 Hz, 9H), 0.96-0.82 (m, 6H). FT-IR (film) 3508,
1736, 1694, 1605, 1160, 698 cm-1. ESI-MS m/z (%) 379.2 (M+,
0.5), 361 (0.5), 346 (7.1), 320 (11.2), 292 (16.3), 275 (26.9), 263
(42.8), 248 (55.9), 196 (84.4), 180 (100). ESI-HRMS calcd for
C20H29NO2S2Na ([M + Na]+) 402.1532; found 402.1548.
Da ta for Com p ou n d 31. A colorless oil: [R]23D +8.13 (c 0.55,
Da ta for Com p ou n d 22. A colorless oil: [R]27D +7.32 (c 0.20,
CHCl3). 1H NMR δ 7.36-7.24 (m, 5H), 5.13 (d, J ) 12.5 Hz, 2H),
5.10 (d, J ) 12.5 Hz, 1H), 4.01 (dd, J ) 5.5, 10.9 Hz, 1H), 2.58
(br quint, J ) 6.1 Hz, 1H), 1.45-1.24 (m, 8H), 1.15 (d, J ) 7.0
Hz, 3H), 0.93 (t, J ) 8.0 Hz, 9H), 0.57 (q, J ) 8.0 Hz, 6H). FT-
IR (film) 1736, 1457, 742 cm-1. ESI-MS m/z 379.2 ([M + 1]+).
ESI-HRMS calcd for C22H38O3SiNa ([M + Na]+) 401.2482; found
401.2500.
1
CHCl3). H NMR δ 6.20-5.40 (very br lump, 1H), 3.97 (m, 1H),
2.61 (dq, J ) 7.1, 3.2 Hz, 1H), 1.49-1.31 (m, 8H), 1.20 (d, J )
7.1 Hz, 3H), 0.89 (t, J ) 6.4 Hz, 3H). FT-IR (film) 3445, 1736,
1460, 1379, 1181 cm-1. ESI-MS m/z 197.1 ([M + Na]+), 192.1-
([M + NH4]+). EI-HRMS calcd for C9H18O3 (M+) 174.1256; found
174.1243.
Da ta for Com p ou n d 23. A colorless oil: [R]18D -197.8 (c 1.35,
1
CHCl3). H NMR δ 7.38-7.27 (m, 5H), 5.94 (d, J ) 7.5 Hz, 1H),
5.42 (dt, J ) 10.5, 2.5 Hz, 1H), 5.05 (dd, J ) 7.7, 3.1 Hz, 1H),
4.10 (dd, J ) 10.9, 7.3 Hz, 1H), 3.95 (dq, J ) 5.8, 11.8 Hz, 1H),
3.02 (dd, J ) 0.8, 11.0 Hz, 1H), 2.19 (d, J ) 5.9 Hz, 2H), 2.03-
2.15 (m, 1H), 1.90-1.75 (m, 1H), 1.60-1.45 (m, 1H), 1.40-1.10
(m, 4H), 1.16 (d, J ) 6.0 Hz, 3H), 1.04-0.92 (m, 9H), 0.64 (br q,
Ack n ow led gm en t. This work has been supported
by the National Natural Science Foundation of China
(20025207, 20272071, 20372075, 20321202), the Chinese
Academy of Sciences (“Knowledge Innovation” Project,
KGCX2-SW-209), and the Major State Basic Research
Development Program (G2000077502).
J ) 8.0 Hz, 6H). FT-IR (film) 1733, 1703, 1455, 1163, 744 cm-1
.
ESI-MS m/z 588 ([M + Na]+). Anal. Calcd for C29H47NO4S2Si:
C, 61.55; H, 8.37; N, 2.48. Found: C, 61.72; H, 8.48; N, 2.35.
Da ta for Com p ou n d 24. A colorless oil: [R]30D +14.5 (c 1.37,
CHCl3). 1H NMR δ 7.41-7.24 (m, 5H), 5.14 (dd, J ) 5.2, 7.3 Hz,
1H), 5.14 (d, J ) 12.5 Hz, 1H), 5.08 (d, J ) 12.5 Hz, 1H), 3.78
(br quint, J ) 5.5 Hz, 1H), 2.68 (ddd, J ) 14.3, 8.3, 3.7 Hz, 1H),
2.19 (d, J ) 5.8 Hz, 2H), 2.03-2.13 (m, 1H), 1.72-1.40 (m, 2H),
1.10 (d, J ) 6.0 Hz, 3H), 0.95 (d, J ) 6.5 Hz, 6H), 0.91 (t, J )
7.9 Hz, 9H), 0.54 (q, J ) 7.9 Hz, 6H). FT-IR (film) 1740, 1453,
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
all new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O049204E
6144 J . Org. Chem., Vol. 69, No. 18, 2004