Organic Syntheses, Vol. 76, 37
Checked by William Moser and Amos B. Smith, III.
1. Procedure
2. Notes
1.
1,3-Dithiane was stored in a
desiccator over self-indicating
silica gel.
3.
Sodium hexamethyldisilazide [
sodium bis(trimethylsilyl)amide] was purchased from the Aldrich Chemical Company, Inc., in 100- or 800-mL bottles as a 1 M solution in
tetrahydrofuran. Glassware used for moisture sensitive reactions was dried at 180°C and allowed to cool in a desiccator over self-indicating silica gel. Reactions were carried out under a slight positive static pressure of
argon.
4.
Butyllithium was purchased from the Aldrich Chemical Company, Inc., in 800-mL bottles as a 2.5 M solution in hexanes; the molarity was determined by titration against a solution of
diphenylacetic acid.
5. Commercially available reagents were used as supplied unless otherwise stated.
7.
Petroleum ether (40-60°C) was distilled prior to use.
8. The analytical data for
2-(2,2-dimethylpropanoyl)-1,3-dithiane are as follows: Found: C, 52.73; H, 7.87. C
9H
16OS
2 requires C, 52.90; H, 7.89%; IR (Nujol) cm
−1: 2900, 1673;
1H NMR (400 MHz, CDCl
3) δ: 1.24 (s, 9 H), 1.95-2.09 (m, 1 H), 2.13-2.23 (m, 1 H), 2.56 (ddd, 2 H, J = 2.4, 7.0, 12.5), 3.43 (dt, 2 H, J = 2.4, 12.5), 4.51 (s, 1 H); m/z (El) 204.06445 (M
+); C
9H
16OS
2 requires 204.06425.
9. For the preparation of
(+)-[(8,8-dimethoxycamphoryl)sulfonyl]oxaziridine see: Chen, B.-C.; Murphy, C. K.; Kumar, A.; Reddy, R. T.; Clark, C.; Zhou, P.; Lewis, B. M.; Gala, D.; Mergelsberg, I.; Scherer, D.; Buckley, J.; DiBenedetto, D.; Davis, F. A.
Org. Synth., Coll. Vol. IX 1998, 212. A somewhat modified procedure
3 is as follows:
(+)-[(8,8-Dimethoxycamphoryl)sulfonyl]oxaziridine.
Aliquat 336® (tri-n-octyl-methylammonium chloride) (5.0 mL, 10.9 mmol) is added to a stirred solution of
50.0 g (183 mmol) of (+)-[(8,8-dimethoxycamphoryl)sulfonyl]imine in
250 mL of dichloromethane at 0°C. A solution of
50.0 g (362 mmol) of potassium carbonate in 100 mL water is added and the biphasic reaction mixture is stirred for 5 min. A commercial solution
(30% w/v) of hydrogen peroxide (83.0 mL, 732 mmol) is added dropwise over 30 min. The reaction is then allowed to warm to room temperature and stirred for about 6-7 hr (Note
15). The organic layer is separated and the aqueous phase extracted three times, each with
100 mL of dichloromethane. Residual
hydrogen peroxide in the aqueous phase is carefully destroyed by the addition of
saturated aqueous sodium sulfite. The combined organic extracts are rapidly washed with an aqueous solution of
5.0 g of sodium sulfite in 100 mL water and
100 mL of saturated brine and dried over
anhydrous magnesium sulfate. Removal of the solvent under reduced pressure, at a bath temperature not exceeding 40°C, gives a white solid consisting of
(+)-[(8,8-dimethoxycamphoryl)sulfonyl]oxaziridine contaminated with
(+)-[(8,8-dimethoxycamphoryl)sulfonyl]imine. Recrystallization from
absolute ethanol furnishes
51.3 g (
97%) of
(+)-[(8,8-dimethoxycamphoryl)sulfonyl]oxaziridine, mp
188-190°C (Note
16).
11. The analytical data for
anti- and syn-1S-(2,2-dimethylpropanoyl)-1,3-dithiane 1-oxides are as follows: Found: C, 48.91; H, 7.35. C
9H
16O
2S
2 requires C, 49.06; H, 7.32; IR (Nujol) cm
−1: 2900, 1706, 1030;
1H NMR (400 MHz, CDCl
3) δ for anti-: 1.26 (s, 9 H), 2.04-2.15 (m, 1 H), 2.45-2.70 (m, 2 H), 2.75-2.90 (m, 2 H), 3.44-3.56 (m, 1 H), 4.72 (s, 1 H); for syn-: 1.24 (s, 9 H), 2.22-2.35 (m, 1 H), 2.45-2.55 (m, 2 H), 3.00-3.15 (m, 2 H), 3.97 (dt, 1 H, J = 3.5, 13.8), 4.98 (s, 1 H); m/z (EI) 220.05931 (M
+); C
9H
16OS
2 requires 220.059187; ee (anti) = 87%, ee (syn) = 88% from
1H NMR studies (Note
17).
12.
Ethanol was used as supplied without further purification.
13. The analytical data for
1S-(−)-1,3-dithiane 1-oxide are as follows: Found: C, 35.18; H, 5.93. C
4H
8OS
2 requires C, 35.27; H, 5.89; IR (Nujol) cm
−1: 2927, 1047;
1H NMR (400 MHz, CDCl
3) δ: 2.10-2.35 (m, 1 H), 2.45-2.77 (m, 4 H), 3.35 (ddd, 1 H, J = 3.0, 6.0, 9.5), 3.66 (d, 1 H, J = 12.7), 4.03 (d, 1 H, J = 12.7); m/z (EI) 136.00151 (M
+); C
4H
8OS
2 requires 136.00166; ee = 87% from
1H NMR studies (Note
17).
14. The checkers obtained the product in about
54% yield and found flash chromatography to be more effective in its purification. This was accomplished using a
16-cm × 5-cm column of silica gel and CHCl3/MeOH (96:4) as the eluant. With collection of ca. 50-mL fractions, the product was observed in fractions 12-21. Visualization of the product was accomplished by TLC (product R
f = 0.4 in CHCl
3/MeOH 96:4,
anisaldehyde stain).
15. The checkers noted that complete oxidation typically required ca. 6-7 hr and recommend checking the progress of the reaction in the following way: a 1-mL aliquot is removed from the organic layer, diluted with 2 mL of
methylene chloride, and analyzed by TLC eluting with
methylene chloride (I
2 visualization); imine R
f = 0.34,
oxaziridine R
f = 0.51
16. The analytical data for
(+)-[(8,8-dimethoxycamphoryl)sulfonyl]oxaziridine are as follows: Found: C, 49.77; H, 6.62; N, 4.88. C
12H
19NO
5S requires C, 49.83; H, 6.57; N, 4.84; IR (CH
2Cl
2 film) cm
−1: 1367, 1345, 1165;
1H NMR (400 MHz, CDCl
3) δ: 1.06 (s, 3 H), 1.32 (s, 3 H), 1.75-2.30 (m, 5 H), 3.08 (d, 1 H, J = 12.0), 3.29 (d, 1 H, J = 12.0), 3.27 (s, 3 H), 3.34 (s, 3 H, CH
3);
13C NMR (100 MHz, CDCl
3) δ: 20.5, 21.6, 28.1, 29.3, 45.1, 47.4, 52.9, 50.5, 50.8, 54.6, 97.6, 102.8; m/z (CI) 290.10619 (MH
+); C
12H
20NO
5S requires 290.10622;
[α]20D +91° (CHCl
3,
c 3.00) (Note
17).
17. Optical rotations were measured on Optical Activity AA-1000 or polAAr 2001 polarimeters operating at 589 nm, corresponding to the
sodium D line. Enantiomeric excesses were determined by
1H NMR chiral shift reagent studies using 10 equiv of
(R)-(−)- or (S)-(+)-2,2,2-trifluoro-1-(9-anthryl)ethanol (Pirkle reagent).
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
Non-racemic chiral sulfoxides have become important as sources of chirality for asymmetric carbon-carbon bond formation.
4 For example, we have developed 1,3-dithiane 1-oxide (DiTOX) units as effective moieties for stereocontrol of a range of carbonyl group reactions, including enolate alkylation and amination, Mannich reaction, reduction, and heterocycloaddition.
5 While we have been able to prepare several 2-monosubstituted
6 and 2,2-disubstituted-1,3-dithiane 1-oxides
7 in high enantiomeric excesses (ee) on scales of a few grams, we had difficulty until recently in preparing the parent compound,
1,3-dithiane 1-oxide, with very high ee in quantities of more than ca. 5 g.
8 Enantiomerically pure
1,3-dithiane 1-oxide has previously been prepared via adducts with
(+)-camphor,
9 and, by ourselves, using modified Sharpless oxidation techniques.
8,10,11
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
1S-(−)-1,3-Dithiane 1-oxide: 1,3-Dithiane, 1-oxide, (S)- (10); (63865-78-1)
2-(2,2-Dimethylpropanoyl)-1,3-dithiane: 1-Propanone, 1-(1,3-dithian-2-yl)-2,2-dimethyl- (10); (73119-31-0)
1,3-Dithiane: m-Dithiane (8); 1,3-Dithiane (9); (505-23-7)
Sodium hexamethyldisilazide (NHMDS): Aldrich: Sodium bis(trimethylsilyl)amide: Disilazane, 1,1,1,3,3,3-hexamethyl-, sodium salt (8); Silanamine, 1,1,1-trimethyl-N-(trimethylsilyl)-, sodium salt (9); (1070-89-9)
Butyllithium: Lithium, butyl- (8,9); (109-72-8)
Ethyl 2,2-dimethylpropanoate: Aldrich: See: Ethyl trimethylacetate: Propanoic acid, 2,2-dimethyl-, ethyl ester (9); (3938-95-2)
anti-1S-(2,2-Dimethylpropanoyl)-1,3-dithiane 1-oxide: 1-Propanone, 2,2-dimethyl-1-(1-oxido-1,3-dithian-2-yl)-, (1S-trans)- (13); (160496-17-3)
(+)-[(8,8-Dimethoxycamphoryl)sulfonyl]oxaziridine: 4H-4a,7-Methanooxazirino[3,2-i][2,1]benzisothiazole, tetrahydro-8,8-dimethoxy-9,9-dimethyl-, 3,3-dioxide, [2R-(2α,4aα,7α, 8aR)]- (12); (131863-82-6)
Aliquat 336: Methyltri-n-octylammonium chloride: Ammonium, methyltrioctyl-, chloride (8); 1-Octanaminium, N-methyl-N,N-dioctyl-, chloride (9); (5137-55-3)
Hydrogen peroxide (8,9); (7722-84-1)
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