Org. Synth. 1998, 75, 139
DOI: 10.15227/orgsyn.075.0139
PHOTOINDUCED-ADDITION OF METHANOL TO (5S)-(5-O-tert-BUTYLDIMETHYLSILOXYMETHYL)FURAN-2(5H)-ONE: (4R,5S)-4-HYDROXYMETHYL-(5-O-tert-BUTYLDIMETHYLSILOXYMETHYL)FURAN-2(5H)-ONE
[
2(5H)-Furanone, 5-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-, (S)- and D-erythro-Pentonic acid, 2,3-dideoxy-5-O-[(1,1-dimethylethyl)dimethylsilyl]-3-(hydroxymethyl)-, γ-lactone
]
Submitted by John Mann and Alexander C. Weymouth-Wilson
1
.
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]
D
20 −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]
D
20 −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]
D
20 +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]
D
20 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]
D
20 values from −140° to −154.5°.
7.
Dichloromethane was dried over
phosphorus pentoxide
.
8.
tert-Butyldimethylsilyl chloride was purchased from Aldrich Chemical Company, Inc.
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)
.
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
3. Discussion
The photoinduced-addition of alcohols to cycloalkenones has been investigated by Fraser-Reid and co-workers,
4 by Paquette,
5 and was used as the key step in the synthesis of the prostaglandin endoperoxide analogue
(15S)-hydroxy-9α,11α-epoxymethanoprosta-(5Z,13E)-dienoic acid,
6 and for the recent synthesis of
2',3'-dideoxy-3'-hydroxymethyl-5'-carbanucleosides.
7 No work (other than our own) has been reported on the photoinduced-addition of alcohols to 5-substituted furan-2(5H)-ones.
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.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
(5S)-(5-O-tert-Butyldimethylsiloxymethyl)furan-2(5H)-one:
2(5H)-Furanone, 5-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-, (S)- (11); (105122-15-4)
(4R,5S)-4-Hydroxymethyl-(5-O-tert-butyldimethylsiloxymethyl)furan-2(5H)-one:
D-erythro-Pentonic acid, 2,3-dideoxy-5-O-[(1,1-dimethylethyl)dimethylsilyl]-3-hydroxymethyl)-, γ-lactone (13); (164848-06-0)
L-(S)-Glyceraldehyde acetonide:
1,3-Dioxolane-4-carboxaldehyde, 2,2-dimethyl-, L- (8);
1,3-Dioxolane-4-carboxaldehyde, (S)- (9); (22323-80-4)
Methyl (triphenylphosphoranylidene)acetate:
Acetic acid, (triphenylphosphoranylidene), methyl ester (8);
Propanoic acid, 2-(triphenylphosphoranylidene)-, methyl ester (9); (2605-67-6)
Methyl (4S)-4,5-O-isopropylidenepent-(2Z)-enoate:
2-Propenoic acid, 3-(2,2-dimethyl-1,3-dioxolan-4-yl)-, methyl ester, [S-(Z)]- (11); (81703-94-8)
(S)-5-Hydroxymethylfuran-2(5H)-one:
2(5H)-Furanone, 5-(hydroxymethyl)-, (S)- (10); (78508-96-0)
tert-Butyldimethylsilyl chloride:
Silane, chloro(1,1-dimethylethyl)dimethyl- (9);
(18162-48-6)
Benzophenone (8);
Methanone, diphenyl- (9); (119-61-9)
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