April 2002
561
(RS,S or SS,S)-N-Diphenylmethyl-2-[2-(4-isopropyl-2-thioxothiazolidin-
37% total yield) of rac-2 and rac-3 in a ratio of 2 : 98. Pure rac-3 was ob-
3-yl)-2-oxo-ethylsulfinyl]acetamide [(RS,S)-12] or [(SS,S)-12] To a solu- tained by recrystallization of the crude compound in n-hexane–CHCl3. Col-
tion of 11 (208.1 mg, 0.66 mmol) in 1,1,1,3,3,3-hexafluoro-2-propanol (1.6 orless crystals; mp 94—96 °C. 1H-NMR (200 MHz, CDCl3) d: 1.88 (3H, s),
ml) was added 30% H2O2 (0.15 ml, 1.37 mmol), and then the mixture was 3.45 (1H, d, Jϭ16.1 Hz), 3.56 (1H, d, Jϭ16.1 Hz), 3.67 (3H, s), 6.26 (1H, d,
stirred at room temperature under N2 for 3 h. After treating with 10% Jϭ8.1 Hz), 7.28—7.31 (11H, m). IR (KBr) cmϪ1: 1746, 1640, 699. EI-MS
Na2SO3, the resultant solution was evaporated in vacuo to give an oily m/z: 387.1184 (Calcd for C20H21NO5S: 387.1140). Anal. Calcd for
residue. To a solution of the residue in CH2Cl2 (6.6 ml) were successively C20H21NO5S: C, 62.00; H, 5.46; N, 3.62. Found: C, 61.93; H, 5.61; N, 3.56.
added 4(S)-isopropyl-1,3-thiazolidine-2-thione (127.3 mg, 0.79 mmol), EDC·
Entry 3 in Table 1: The Pummerer reaction of (SS)-1 (99% ee, 35 mg,
HCl (191.1 mg, 1.00 mmol), and DMAP (8.2 mg, 0.07 mmol). The entire 0.1 mmol) was similarly carried out using Ac2O (48 ml, 0.5 mmol) and TM-
mixture was stirred at room temperature under N2 for 1 h and then treated SOTf (59 ml, 0.3 mmol) in DMF (1 ml) to give a mixture (33.3 mg, 85% total
with 1 N HCl (10 ml). The acidic solution was extracted with CHCl3 (10 mlϫ
3 times) and the extract was submitted to the usual workup to give a yellow the major product, chiral-3, was determined to be 53% by H-NMR (300
yield) of chiral-2 and chiral-3 in a ratio of 4 : 96. The enantiomeric excess of
1
residue. The residue was chromatographed on a silica gel column with MHz, CDCl3) analysis using a chiral shift reagent, Eu(hfc)3.
AcOEt–n-hexane (1 : 1) to give (RS,S)-12 (70.7 mg, 23%) and (SS,S)-12
Entry 4 in Table 1: The Pummerer reaction of (RS)-1 (85% ee, 50 mg,
(72.3 mg, 23%) as yellow needles (AcOEt), respectively. (RS,S)-12: mp 0.14 mmol) with Ac2O (71 ml, 0.72 mmol) and TMSOTf (81 ml, 0.45 mmol)
133.5—135 °C (dec.). [a]D25 ϩ244.8° (cϭ1.00, CHCl3). 1H-NMR (200 MHz, in the presence of 1,3-dicyclohexylcarbodiimide (120 mg, 0.58 mmol) in
CDCl3) d: 0.96 (3H, d, Jϭ6.8 Hz), 1.04 (3H, d, Jϭ6.8 Hz), 2.04—2.37 (1H, CH2Cl2 (2 ml) gave a mixture (31.9 mg, 57% total yield) of chiral-2 and, chi-
m), 3.03 (1H, d, Jϭ11.5 Hz), 3.53—3.67 (1H, m), 3.56 (1H, d, Jϭ13.9 Hz), ral-3, in a ratio of 4 : 96. The enantiomeric excess of the major product, chi-
1
3.79 (1H, d, Jϭ13.9 Hz), 4.69 (1H, d, Jϭ16.4 Hz), 4.88 (1H, d, Jϭ16.4 Hz), ral-3, was determined to be 29% by H-NMR (300 MHz, CDCl3) analysis
5.03 (1H, t, Jϭ6.6 Hz), 6.26 (1H, d, Jϭ8.3 Hz), 7.23—7.31 (10H, m), 7.6 using a chiral shift reagent, Eu(hfc)3.
(1H, d, Jϭ8.3 Hz). IR (KBr) cmϪ1: 1666, 1244, 1044. FAB-MS m/z:
475.1136 (Calcd for C23H27N2O3S3: 475.1184). Anal. Calcd for C23H26N2O3S3:
Entry 5 in Table 1: To a solution of (RS)-1 (85% ee, 50 mg, 0.14 mmol) in
CH2Cl2 (2 ml) was added lithium bis(trimethylsilyl)amide [(TMS)2NLi] (1 M
C, 58.20; H, 5.52; N, 5.90. Found: C, 58.08; H, 5.53; N, 5.76. (SS,S)-12: mp n-hexane solution 145 ml, 0.14 mmol) at Ϫ40 °C under N2, and then the mix-
143—144.5 °C (dec.). [a]D25 ϩ153.8° (cϭ1.02, CHCl3). 1H-NMR (200 MHz, ture was stirred at Ϫ40 °C under N2 for 30 min. After successive addition of
CDCl3) d: 0.97 (3H, d, Jϭ6.8 Hz), 1.04 (3H, d, Jϭ6.6 Hz), 2.29—2.35 (1H, Ac2O (71 ml, 0.72 mmol) and TMSOTf (81 ml, 0.45 mmol), the entire mix-
m), 3.06 (1H, d, Jϭ11.7 Hz), 3.50—3.63 (1H, m), 3.60 (1H, d, Jϭ13.9 Hz), ture was stirred at Ϫ40 °C for 17 h, followed by treatment with an aqueous
3.84 (1H, d, Jϭ13.9 Hz), 4.60 (1H, d, Jϭ16.4 Hz), 4.91 (1H, d, Jϭ16.4 Hz), solution saturated with NaHCO3. The resultant solution was extracted with
5.10 (1H, t, Jϭ6.6 Hz), 6.29 (1H, d, Jϭ8.3 Hz), 7.26—7.32 (10H, m), 7.68 AcOEt, and the extract was submitted to the typical workup to give an oily
(1H, d, Jϭ8.3 Hz). IR (KBr) cmϪ1: 1674, 1245, 1036. FAB-MS m/z: residue. PTLC purification of the residue, as described above, gave a mix-
475.1162 (Calcd for C23H27N2O3S3: 475.1184). Anal. Calcd for ture (22.0 mg, 39% total yield) of chiral-2 and chiral-3 in a ratio of 8 : 92.
C23H26N2O3S3: C, 58.20; H, 5.52; N, 5.90. Found: C, 58.53; H, 5.55; N, The enantiomeric excess of the major product, chiral-3, was determined to
6.09.
Conversion of (RS,S)-12 to Methyl (؉)-(R)-[(Diphenylmethylcar-
be 63% by HPLC analysis, as described above.
Entry 6 in Table 1: To a solution of (RS)-1 (99% ee, 50 mg, 0.14 mmol) in
bamoyl)methylsulfinyl]acetate [(RS)-1] To a solution of (RS,S)-12 (2.98 g, CH2Cl2 (2 ml) was added (TMS)2NLi (1 M n-hexane solution 145 ml,
6.27 mmol) in MeOH (6.9 ml) was added MeONa (1 M MeOH solution 6.9 0.14 mmol) at Ϫ78 °C under N2. After being stirred at Ϫ78 °C for 1 h, Ac2O
ml, 6.9 mmol). The mixture was stirred at 0 °C under N2 for 40 min and then (71 ml, 0.72 mmol) was added, and then the mixture was stirred at Ϫ78 °C
treated with 1 N HCl (10 ml). The acidic solution was extracted with AcOEt
for 1 h. To the mixture was added TMSOTf (81 ml, 0.45 mmol) at Ϫ78 °C.
(50 mlϫ3 times), and the extract was submitted to the usual workup to give The entire mixture was warmed to Ϫ40 °C, and stirred at Ϫ40 °C for 12 h.
an oily residue. Chromatographic purification of the residue on a silica gel The same treatment of the reaction mixture, as described in entry 5, afforded
column was carried out using AcOEt–n-hexane (1 : 2 to 3 : 1) to give (RS)-1
a mixture (26.4 mg, 47% total yield) of chiral-2 and chiral-3 in a ratio of
(1.85 g, 86%, 99% ee) as a white powder (acetone–n-hexane). The enan- 7 : 93. The enantiomeric excess of the chiral-3 was determined to be 75% by
tiomeric excess (99%) was determined by HPLC using a CHIRALCEL OD 1H-NMR (300 MHz, CDCl3) analysis using a chiral shift reagent, Eu(hfc)3.
column with n-hexane–2-propanol (2 : 1). All spectroscopic data were identi-
cal to those of the (RS)-1 compound, which was prepared by the enzymatic
Acknowledgements This work was in part supported by a Grant-in-Aid
for Scientific Research (B) (2) (No. 12470482) from the Japan Society for
procedure described above. mp 124—126 °C. [a]D22 ϩ8.1° (cϭ1.05, CHCl3).
Conversion of (SS,S)-12 to Methyl (؊)-(S)-[(Diphenylmethylcar- the Promotion of Science.
bamoyl)methylsulfinyl]acetate [(SS)-1] This reaction was carried out sim-
ilarly, according to the conversion of (RS,S)-12 to (RS)-1 by using (SS,S)-12
(3.03 g, 6.83 mmol) and MeONa (1 M MeOH solution 7 ml, 7.0 mmol); (SS)-
1 (2.0 g, 91%, 99% ee) was obtained as a white powder (acetone–n-hexane).
mp 124—124.5 °C. [a]D22 Ϫ8.1° (cϭ1.07, CHCl3). All spectroscopic data of
(SS)-1 were identical to those of (RS)-1.
References and Notes
1) The authors reported the experimental results at the 25th Symposium
on Heteroatom Chemistry, Kyoto, Japan, 1998, symposium paper, pp.
109—112.
2) Otto H.-H., Schirmeister T., Chem. Rev., 97, 133—171 (1997) and ref-
erences cited therein.
Pummerer Reaction of (RS)-1 and (SS)-1 Entry 1 in Table 1: To a solu-
tion of (RS)-1 (85% ee, 139 mg, 0.4 mmol) in CH2Cl2 (10 ml) were added
Ac2O (190 ml, 2.0 mmol) and TMSOTf (232 ml, 1.3 mmol). The mixture
was stirred at Ϫ40 °C under N2 for 24 h and then treated with an aqueous so-
lution saturated with NaHCO3. The resultant solution was extracted with
AcOEt. The extract was submitted to the usual workup to give an oily
residue. The residue was purified by a PTLC method with AcOEt–n-hexane
(1 : 2) to give a mixture (115.4 mg) of rac-2 and rac-3 in a 74% total yield.
The product ratio, rac-2 : rac-3 (93 : 7) was detrmined by a 1H-NMR
(200 MHz, CDCl3) analysis based on the AcO signals (d 2.17 for rac-2 and
d 1.88 for rac-3). The enantiomeric excess of the major product was deter-
mined to be 0% by the HPLC analysis using a CHIRALCEL OD column
with n-hexane–2-propanol (5 : 1). Pure rac-2 was obtained by recrystalliza-
tion of the crude compound in n-hexane–CHCl3. Colorless needles; mp
111—112 °C. 1H-NMR (200 MHz, CDCl3) d: 2.17 (3H, s), 3.39 (1H, d,
Jϭ13.4 Hz), 3.66 (1H, d, Jϭ13.4 Hz), 3.69 (3H, s), 6.24 (1H, d, Jϭ8.3 Hz),
7.26—7.34 (11H, m). IR (KBr) cmϪ1: 1746, 1657, 700. EI-MS m/z:
387.1138 (Calcd for C20H21NO5S: 387.1140). Anal. Calcd for C20H21NO5S:
C, 62.00; H, 5.46; N, 3.62. Found: C, 61.88; H, 5.51; N, 3.51.
3) a) Jonsson E., Tetrahedron Lett., 1967, 3675—3678; b) Numata T.,
Itoh O., Oae S., ibid., 1977, 909—912; c) Wolfe S., Kazmaier P. M.,
Can. J. Chem., 57, 2397—2403 (1979); d) Simada K., Kikuta Y., Ko-
ganebuchi H., Yonezawa F., Aoyagi S., Takikawa Y., Tetrahedron Lett.,
41, 4637—4640 (2000).
4) a) Numata T., Itoh O., Oae S., Tetrahedron Lett., 1979, 1869—1870;
b) Numata T., Itoh O., Yoshimura T., Oae S., Bull. Chem. Soc. Jpn.,
56, 257—265 (1983).
5) a) Kita Y., Shibata N., Kawano N., Fukui S., Fujimori C., Tetrahedron
Lett., 35, 3575—3576 (1994); b) Shibata N., Matsugi M., Kawano N.,
Fukui S., Fujimori C., Gotanda K., Murata K., Kita Y., Tetrahedron:
Asymmetry, 1997, 303—310.
6) Kita Y., Shibata N., Yoshida N., Tetrahedron Lett., 34, 4063—4066
(1993); Kita Y., Shibata N., Yoshida N., Fujita S., J. Chem. Soc.,
Perkin Trans 1, 1994, 3335—3341.
7) Kucsman A., Kapovits I., “Organic Sulfur Chemistry: Theoretical and
Experimental Advances,” ed. by Bernardi F., Csizmadia I. G., Mangini
A., Elsevier, Amsterdum, 1985, pp. 191—245 and references cited
therein.
8) Tamai S., Miyauchi S., Morizane C., Miyagi K., Shimizu H., Kume
M., Sano S., Shiro M., Nagao Y., Chem. Lett., 1994, 2381—2384.
Entry 2 in Table 1: The Pummerer reaction of (RS)-1 (85% ee, 50 mg,
0.14 mmol) was similarly carried out using Ac2O (71 ml, 0.72 mmol) and
TMSOTf (81 ml, 0.45 mmol) in MeCN (2 ml) to give a mixture (20.7 mg,