Checked by Scott Jeffrey and James D. White.
1. Procedure
B.
Acryloyl-2-oxazolidinone (Note 7). A
flame-dried, 1-L, one-necked, round-bottomed flask, equipped with a magnetic stirring bar, is charged with
8.71 g (100 mmol) of 2-oxazolidinone (Note
2), flushed with
argon (Note
8), and then
500 mL of tetrahydrofuran (Note
9) is introduced. The mixture is stirred to dissolve solids, cooled to 0°C, and
33.3 mL (100 mmol) of 3 M methylmagnesium bromide in
ether (Note
2) is slowly added. After the solution is stirred for 10 min at 0°C,
11.6 mL (115 mmol) of 3-bromopropionyl chloride (Note
10) is added dropwise. The cooling bath is removed and the mixture is allowed to warm to ambient temperature over 30 min. The mixture is diluted with
600 mL of peroxide-free ether (Note
11) and washed with saturated aqueous
ammonium chloride. The organic phase is dried over
magnesium sulfate and filtered. To the filtrate, stirred at ambient temperature, is added
69 mL (500 mmol) of triethylamine (Note
1). A colorless precipitate forms immediately and the resulting slurry is stirred at ambient temperature for 3 hr, then poured into a
1:1 mixture of saturated aqueous ammonium chloride and 1 N aqueous hydrochloric acid. The aqueous layer is extracted with
200 mL of peroxide-free ether (Note
11), and the combined organic phases are dried over
magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is subjected to flash chromatography
4 on
150 g of silica gel (Note
5) (
35% ethyl acetate-hexane, v/v) to give
5.81 g (
41%) of
acryloyl-2-oxazolidinone as colorless crystals, mp
82–83°C (Note
12).
C.
Diels-Alder reaction. All reagents and glassware are dried rigorously. A flame-dried,
250-mL, three-necked, round-bottomed flask, equipped with a magnetic stirring bar and a
reflux condenser, is charged with
1.31 g (2.75 mmol) of bistriflamide of (1S,2S)-1,2-diphenylethylenediamine (dried at 80°C and 1 mm) and placed under dry
argon (Note
8).
1,2-Dichloroethane (20 mL) (Note
13) is added, the mixture is heated to 80°C with stirring to effect solution, cooled to ambient temperature, and treated dropwise with
1.37 mL (2.74 mmol) of 2 M trimethylaluminum in
toluene (Note
2). After the evolution of gases ceases, the homogeneous mixture is heated to 80°C (
oil bath) for 3 hr. The heating bath is removed, the mixture is cooled to ambient temperature, the reflux condenser is replaced by a
glass stopper, and the solvent is removed under reduced pressure (
oil pump) that is maintained for an additional 30 min. The resulting solid is dissolved in
10 mL of dry methylene chloride (Note
3) and overlayered with
50 mL of dry heptane. Colorless crystals are deposited after 20 hr. The supernatant liquid is drawn off by syringe and the residual solid is dissolved in
50 mL of methylene chloride (Note
3). The solution is cooled to −78°C and a solution of
7.76 g (55 mmol) of acryloyl-2-oxazolidinone in
50 mL of methylene chloride (Note
3) is introduced through a cannula. The mixture is stirred for 5 min at −78°C and then
5.7 mL (71 mmol) of neat, cold (−78°C) cyclopentadiene (Note
14) is slowly introduced through a cannula (Note
15) along the cooled sides of the flask. Stirring is continued for another 15 min. The mixture is poured into
1 N aqueous hydrochloric acid, the phases are separated, and the aqueous phase is washed with
25 mL of methylene chloride. The combined organic phases are washed successively with aqueous
sodium bicarbonate and
brine, dried over anhydrous
sodium sulfate, and filtered. The filtrate is concentrated under reduced pressure and the residue is subjected to flash chromatography
4 on
150 g of silica gel (Note
5) (
hexane-
ethyl acetate 2:1, v/v) to give
10.1 g (
89%) of the cycloadduct as colorless crystals, mp
68–69°C (Note
16) and (Note
17).
2. Notes
4.
Trifluoromethanesulfonic anhydride was purchased from the Aldrich Chemical Company, Inc., and used as received. It can also be prepared from the acid according to the
Organic Syntheses procedure.
5
5. Kieselgel 60 (230–400 mesh) was purchased from EM Science, an affiliate of E. Merck, Darmstadt.
6. The product has the following properties:
[α]D −6.6° (CHCl
3,
c 1.4);
1H NMR (CDCl
3) δ: 4.81 (s, 2 H), 6.80 (bs, 2 H), 7.25 (6 H), 7.0 (4 H);
13C NMR (CDCl
3) δ: 63.7, 127.0, 129.1 (2 C), 135.1.
7. This procedure is essentially the same as that described in the literature.
6
8. This procedure involves three consecutive evacuations of the flask and fillings with dry
argon.
12. The product has the following properties: R
f = 3.1 (
35% ethyl acetate in hexane, v/v); IR cm
−1: 1785, 1675, 1419, 1396, 1321, 1258, 1220, 1024, 1008, 982, 752;
1H NMR (CDCl
3) δ: 4.09 (t, 2 H, J = 8.0), 4.45 (t, 2 H, J = 8.0), 5.90 (dd, 1 H, J = 10.4, 1.6), 6.56 (dd, 1 H, J = 17.1, 1.6), 7.49 (dd, 1 H, J = 17.1, 10.4);
13C NMR (CDCl
3) δ: 42.6, 62.1, 127.0, 131.6, 153.6, 165.0.
15. Because of the high rate of the cycloaddition reaction it is very important that the
cyclopentadiene solution enter the reaction flask and mix with the acrylate solution at as low a temperature as possible. For this reason it is beneficial to use a short cannula and to introduce the
cyclopentadiene solution onto the wall of the flask that is deeply immersed in a solid CO
2 bath.
16. The product has the following properties:
[α]D −152.0° (CHCl
3,
c 1.5; ee 89%), (lit.
7 [α]D −65° (CHCl
3,
c 1.5; ee 38%); R
f = 0.23 (
hexane-
ethyl acetate 2:1, v/v); IR cm
−1: 2975, 1775, 1696, 1386, 1337, 1279, 1253, 1226, 1111, 1039, 761, 704;
1H NMR (CDCl
3) δ: 1.39–1.50 (m, 3 H), 1.95 (ddd, 1 H, J = 12.6, 9.3, 3.7), 2.93 (m, 1 H), 3.30 (m, 1 H), 3.91–4.00 (m, 3 H), 4.35–4.41 (m, 2 H), 5.87 (dd, 1 H, J = 5.5, 2.8), 6.24 (dd, 1 H, J = 5.5, 3.1);
13C NMR (CDCl
3) δ: 29.5, 42.9 (2 C), 43.2, 46.4, 50.2, 61.9, 131.6, 138.1, 153.4, 174.7.
17. The endo-exo selectivity of the cycloaddition reaction is higher than 50:1, since no signals corresponding to the exo product are observed in the 500 MHz
1H NMR spectrum of the crude or chromatographed product. The optical purity is 89% ee based on comparison with an authentic sample and the literature data.
8 The optical purity is confirmed by a 500 MHz
1H NMR spectrum of the corresponding Mosher ester prepared in two steps: 1.
Lithium aluminum hydride (LiAlH4) reduction in
tetrahydrofuran at room temperature; 2. esterification of the resulting primary alcohol with
(R)-(+)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride9 in the presence of
triethylamine and
DMAP in
methylene chloride at room temperature.
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
This procedure describes the preparation and application of an effective chiral catalyst for the enantioselective Diels-Alder reaction.
25 The catalyst is derived from optically active
1,2-diphenylethylenediamine, the preparation of which (either antipode) is described (
p. 387). The aluminum-based Lewis acid also catalyzes the cycloaddition of crotonoyl oxazolidinones with
cyclopentadiene,
25 and acryloyl derivatives with
benzyloxymethylenecyclopentadiene. The latter reaction leads to optically pure intermediates for synthesis of prostaglandins.
25
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