Organic Syntheses, Vol. 75, 139
Checked by Robert E. Koehler, Steven Wolff, and David L. Coffen.
1. Procedure
(5S)-(5-O-tert-Butyldimethylsiloxymethyl)furan-2(5H)-one(Note
1). An oven-dried,
500-mL, round-bottomed flask is charged with
35.5 g (0.27 mol) of 2,3-O-isopropylidene-D-glyceraldehyde (Note
2) and
250 mL of methanol. The flask is cooled in an
ice bath during the portionwise addition of
96 g (0.28 mol) of methyl (triphenylphosphoranylidene)acetate (Note
3), and the resultant mixture is stirred for 1 hr at 0°C. The solvent is removed on a
rotary evaporator and the residue is refluxed for 30 min with a mixture of
ether:petroleum ether (3:7, 100 mL). The process is repeated three times, the combined extracts are filtered, and the filtrate is concentrated to yield a colorless oil. The oil is purified by silica chromatography [
1 kg of silica,
8.5-cm × 43-cm column eluting with
ethyl acetate:petroleum ether (3:7)] to yield
39.5 g (
78%) of
methyl (4S)-4,5-O-isopropylidenepent-(2Z)-enoate, and
4.8 g (
10%) of the corresponding trans-isomer, both as colorless oils (Note
4), (Note
5).
A solution of
39.0 g (0.21 mol) of the cis-alkene in
100 mL of methanol is treated with concd
sulfuric acid (ca. 0.8 mL of 30%), and the mixture is stirred for 2 hr at room temperature. Evaporation of the solvent and purification of the residue by silica chromatography (
1 kg of silica, 8.5-cm × 43-cm column with
ethyl acetate as eluant) yield
22.3 g (
93%) of
(S)-5-hydroxymethylfuran-2(5H)-one as a white crystalline solid, mp
40-41°C and
[α]D20 −150.8° (water,
c 2.1) (Note
6).
A solution of 22.0 g of the alcohol (0.19 mol) and
17.6 g (0.26 mol) of imidazole in dichloromethane (Note 7) (100 mL) is cooled in an ice bath, and
36.2 g (0.24 mol) of tert-butyldimethylsilyl chloride (Note
8) is added in one portion. The mixture is stirred for 15 min at 0°C and for a further 20 min at room temperature. Water (200 mL) is then added, and the organic layer is separated. The aqueous layer is extracted with
dichloromethane (3 × 50 mL), and the combined organic extracts are dried over
sodium sulfate prior to evaporation of the solvent. Purification of the residue by silica chromatography [
1 kg of silica, 8.5-cm × 43-cm column eluting with
ethyl acetate:
petroleum ether (3:7)] yields
45 g (ca.
100%) of
(5S)-(5-O-tert-butyldimethylsiloxymethyl)furan-2(5H)-one as a colorless solid, mp
31°C and
[α]D20 −146° (in
chloroform,
c 0.2) (Note
9).
(4R,5S)-4-Hydroxymethyl-(5-O-tert-butyldimethylsiloxymethyl)furan-2(5H)-one. A
1-L Pyrex vessel is charged with
29.5 g (0.13 mol) of (5S)-(5-O-tert-butyldimethylsiloxymethyl)furan-2(5H)-one,
23.7 g (0.13 mol) of benzophenone (Note
10) and
800 mL of methanol. The vessel is placed in a water-cooled, immersion-irradiation apparatus (Note
11), and the solution is degassed for 1 hr in a stream of
nitrogen. It is then irradiated using
two 125-watt, 350-nm lamps; the reaction is complete after 48 hr (Note
12). The solvent is evaporated and the residue is purified by silica chromatography [
1 kg of silica, 8.5-cm × 43-cm column with a gradient elution from
ethyl acetate:
petroleum ether (1:1) to neat
ethyl acetate]. This yields
18.5 g (
55%) of the title compound,
18.3 g (
77%) of recovered
benzophenone,
3.6 g of
benzpinacol, and
1.56 g (
3%) of the photoadduct
(4R,5S)-4-diphenylhydroxymethyl-5-tert-butyldimethylsiloxymethylfuran-2(5H)-one. The title photoadduct is an oil with
[α]D20 +3.2° (in
chloroform,
c 2.0) (Note
13).
2. Notes
1.
(5S )-(5-O-tert-Butyldimethylsiloxymethyl)furan-2(5H)-one has been prepared by a number of groups.
2 They report mp of
31-32°C and
31°C, and
[α]D20 of −141° and −139°.
3. This compound was purchased from Aldrich Chemical Company, Inc.
4. The submitters report that they currently use
two 500-g columns run consecutively. After the first column is used, it is washed with
methanol, all traces of solvent flushed through with compressed air, reequilibrated with eluant, then those fractions (from the first column) that contain a mixture of cis- and trans-alkenes are rechromatographed.
5. The cis-alkene has the following spectral features: IR (thin film) cm
−1: 1725, 1650, 1210, 1065;
1H NMR (220 MHz, CDCl
3) δ: 1.40 and 1.46 (2 s, 6 H, 2 × Me), 3.65 (dd, 1 H, J
gem 8.5, J
4,5 7, 5-H), 3.75 (s, 3 H, OMe), 4.40 (dd, 1 H, J
4,5 7, 5-H), 5.52 (m, 1 H, 4-H), 5.88 (dd, 1 H, J
2,3 11.5, J
2,4 1.5, 2-H), 6.39 (dd, 1 H, J
2,3 11.5, J
3,4 6.5, 3-H).
6.
(S)-5-Hydroxymethylfuran-2(5H)-one has the following spectral data: IR (KBr disc) cm
−1: 3420, 1790, 1605, 1170, 1115, 1080, 1060, 865;
1H NMR (200 MHz, CDCl
3) δ: 3.70-4.06 (m, 3 H, 5-H and OH), 5.19 (m, 1 H, 4-H), 6.20 (dd, 1 H, J
2,3 5.5, J
2,4 2, 2-H), 7.56 (dd, 1 H, J
2,3 5.5, J
3,4 1.5, 3-H). This compound is available from Aldrich Chemical Company, Inc., and has been prepared by a number of other groups.
3 They report mp ranging from
39° to 42°C, and
[α]D20 values from −140° to −154.5°.
9. Spectral data for the silyl ether are as follows: IR (nujol mull) cm
−1: 1747, 1605, 1473, 1331, 1135, 1016, 888;
1H NMR (250 MHz, CDCl
3) δ: 0.02 (s, 3 H, Me), 0.03 (s, 3 H, Me), 0.83 (s, 9 H, tert-Bu), 3.76 (dd, 1 H, J
gem 10.8, J
4,5 5, 5-H), 3.86 (dd, 1 H, J
4,5 5-H), 5.04 (m, 1 H, 4-H), 6.11 (dd, 1 H, J
2,3 5.7 J
2,4 1.95, 2-H), 7.49 (dd, 1 H, J
2,3 5.7, J
3,4 1.4, 3-H).
10. Use of less than one equivalent of
benzophenone increases the photolysis time.
11. The checkers employed a Hanovia
450W medium-pressure mercury arc lamp with an uranium glass filter, a
Pyrex immersion well, and a
1-L irradiation vessel (all available from Ace Glass).
12. Use of
larger wattage lamps decreases the photolysis time.
13. Spectral data for the photoadduct are as follows: IR cm
−1: 3430, 1760, 1470, 1410, 1380, 1258, 1121, 1020, 940, 875, 838, 778;
1H NMR (400 MHz, CDCl
3) δ: 0.04 (s, 3 H, Me), 0.05 (s, 3 H, Me), 0.86 (s, 9 H, tert-Bu), 2.29 (dd, 1 H, J
gem 17, J
3,4 4.6, 3-H), 2.63 (m, 2 H, 4-H and OH), 2.69 (dd, 1 H, J
3,4 9.4, 3-H), 3.60 (dd, 1 H, J
gem 10.5, J
4,7 6.6, 7-H), 3.66 (dd, 1 H, J
4,7 5.2, 7-H), 3.72 (dd, 1 H, J
gem 11.2, J
5,6 2.9, 6-H), 3.83 (dd, 1 H, J
5,6 3.7, 6-H), 4.39 (dt, 1 H, J
5,6 3.7, J
4,5 3.2, 5-H).
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
The reaction appears to be general and the additions are regiospecific and stereoselective. The product from the reaction with
2-propanol has been used for the synthesis of
cis-chrysanthemic acid,
8 and the product with
methanol has been used for the construction of novel
2',3'-dideoxy-3'-hydroxymethylnucleosides.
9 In addition,
ethane-1,2-diol provides the expected photoadduct as a 1:1 mixture of the two possible diastereoisomers, and these can be easily separated as their acetonides, to provide compounds with three contiguous chiral centers emanating from furan-ones with only one chiral center.
9 More recently, we have shown that photoinduced-additions also occur with cyclic amines
10 and these reactions provide access to the skeletons of the pyrrolizidine and indolizidine alkaloids in a concise and stereochemically efficient fashion.
These photoinduced reactions proceed in fair to good yields (50-80%) and tolerate a variety of protecting groups at C-6, e.g., acetate, benzoate, methyl, and benzyl.
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