Organic Syntheses, CV 9, 207
[Benzene, [(2,3-dibromo-1-propenyl)sulfonyl]-, Furan, 2-methyl-4-[(phenylsulfonyl)methyl]-, and 2-Cyclopenten-1-one, 2-methyl-3-[(phenylsulfonyl)methyl]-]
Submitted by Scott H. Watterson, Zhijie Ni, Shaun S. Murphree, and Albert Padwa
1.
Checked by Huguette Vanlierde, Amy Dekoker, and Leon Ghosez.
1. Procedure
A.
1-(Phenylsulfonyl)-1,2-propadiene. In a
1-L, three-necked, round-bottomed flask equipped with a
magnetic stirring bar,
100-mL addition funnel, and a septum fitted with a
nitrogen inlet, are placed
10.5 mL (0.18 mol) of propargyl alcohol (Note
1),
30.1 mL (0.22 mol) of triethylamine, and
700 mL of dichloromethane. The flask is cooled with an
ice-water bath and
26.0 g (0.18 mol) of phenylsulfenyl chloride (Note 2) in 50 mL of dichloromethane is added under a
nitrogen atmosphere from the addition funnel. After the solution is warmed to room temperature and stirred for 3 hr, the mixture is washed with water (2 × 200-mL) and then concentrated under reduced pressure. The resulting residue (ca. 37 g) is dissolved in
100 mL of acetic acid in a
500-mL, round-bottomed flask fitted with a magnetic stirring bar, an addition funnel, and a
thermometer. The solution is heated to 95°C and then
40 mL of hydrogen peroxide (30–35%) (Note
3) is slowly added over a 20-min period maintaining the internal temperature in the flask below 95°C. The mixture is heated for an additional 10 hr, maintaining the external temperature at 95°C (Note
4). After being cooled to 25°C, the mixture is poured into 200 mL of water, and extracted with
dichloromethane (3 × 100 mL). The organic layer is washed with water (2 × 100 mL) followed by saturated
sodium bicarbonate solution (100 mL), dried over
magnesium sulfate, and filtered. The filtrate is concentrated to give
28.1 g (
68%) of
1-(phenylsulfonyl)-1,2-propadiene as an oil, which is used in the next step (Note
5), (Note
6).
2. Notes
4. For the next 30–60 min the internal temperature should not be allowed to exceed 95°C.
5. The submitters were able to obtain most of this product as a crystalline solid that could be recrystallized from
ether at −20°C, mp
44–45°C [lit.
2 mp
44–45°C]. It has the following spectral properties:
1H NMR (300 MHz, CDCl
3) δ: 5.40 (d, 2 H, J = 6.3), 6.21 (t, 1 H, J = 6.3), 7.47–7.87 (m, 5 H);
13C NMR (75 MHz, CDCl
3) δ: 84.0, 100.7, 127.3, 129.0, 133.4, 140.9, 209.2.
6. The checkers were not able to purify the crude oil. As a result their overall yield of final product was 40%. The submitters obtained a 71% overall yield using the crystalline material.
7. This product contains a mixture of E- and Z-isomers in a 7:3 ratio, which could be separated by flash chromatography on silica gel eluting with
hexane:
ethyl acetate (4:1). The spectral properties of both isomers are as follows: E-isomer: mp
62–63°C (recrystallized from
ether);
1H NMR (300 MHz, CDCl
3) δ: 4.96 (s, 2 H), 6.78 (s, 1 H), 7.50–8.15 (m, 5 H);
13C NMR (75 MHz, CDCl
3) δ: 29.8, 127.8, 129.6, 133.7, 134.4, 137.6, 139.6; Anal. Calcd for C
9H
8Br
2O
2S: C, 31.79; H, 2.37. Found: C, 31.86; H, 2.36. Z-Isomer (oil);
1H NMR (300 MHz, CDCl
3) δ: 4.20 (s, 2 H), 7.31 (s, 1 H), 7.50–7.95 (m, 5 H);
13C NMR (75 MHz, CDCl
3) δ: 35.7, 127.9, 128.5, 129.1, 133.8, 134.0, 139.4.
8. Both isomers gave similar yields. If the crystalline E-isomer was used, it took about 30 min for the solid to dissolve.
9. This solution was prepared from
sodium and
methanol and could be stored in a
plastic bottle over a period up to several months without any effect on the reaction.
10. The product has the following spectral properties; mp
91–92°C; 1H NMR (300 MHz, CDCl
3) δ: 2.22 (s, 3 H), 4.10 (s, 2 H), 5.91 (s, 1 H), 7.01 (s, 1 H), 7.50–7.95 (m, 5 H);
13C NMR (75 MHz, CDCl
3) δ: 12.9, 53.0, 106.9, 112.5, 127.9, 128.3, 133.1, 137.3, 140.3, 152.6. Anal. Calcd for C
12H
12O
3S: C, 61.00; H, 5.12. Found: C, 60.91; H, 5.12.
11. The product has the following spectral properties; mp
166–167°C; 1H NMR (300 MHz, CDCl
3) δ: 1.26 (s, 3 H), 2.45 (m, 2 H), 2.73 (m, 2 H), 4.15 (s, 2 H), 7.40–7.95 (m, 5 H);
13C NMR (75 MHz, CDCl
3) δ: 7.2, 29.4, 33.7, 57.9, 127.5, 128.9, 133.7, 137.7, 142.4, 155.8, 207.8. Anal. Calcd. for C
13H
14O
3S: C, 62.38, H, 5.64. Found: C, 62.14, H, 5.47.
Waste Disposal Information
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
Many methods have been devised for the formation of multicyclic furans
3 and cyclopentenones
4 because of their importance in organic synthesis. The procedure described here provides a simple and general approach for the construction of
2-methyl-4-[(phenylsulfonyl)methyl]furan and
2-methyl-3-[(phenylsulfonyl)methyl]-2-cyclopenten-1-one using
2,3-dibromo-1-(phenylsulfonyl)-1,2-propene (DBP) as the key reagent.
5 Addition of
bromine to
1-(phenylsulfonyl)-1,2-propadiene proceeds smoothly at 25°C and can be controlled so that the reaction may be terminated after 1 equiv of
bromine is consumed. The resulting dibromide is a stable, crystalline solid, requiring no special precautions to prevent decomposition.
6 This dibromosulfone can be viewed as a multielectrophilic reagent with great potential as a nucleophilic acceptor for sequential addition. Functionalized allylic reagents that contain both a leaving group and a π-activating substituent have been used extensively in organic synthesis.
7,8,9,10 These substituted 1-propenes have been referred to as multicoupling reagents.
8 Because of the molecular weight and stability of the phenylsulfonyl group, the carbon backbone of DBP is very small, without the drawback of volatility or thermal lability seen in other synthetic intermediates with the same
carbon skeleton. The synthetic potential of DBP is demonstrated here by taking advantage of two properties of the molecule: 1) the ability of the phenylsulfonyl group to activate the double bond toward Michael addition with soft dicarbonyl anions and 2) the facility with which both bromides can be displaced.
Treatment of 1,3-dicarbonyl compounds with DBP in a methoxide/methanol system affords 2-alkyl-4-[(phenylsulfonyl)methyl]furans, where reaction proceeds by initial addition-elimination on the vinyl sulfone moiety. In contrast, silyl enol ethers in the presence of
silver tetrafluoroborate resulted in products derived from S
N2 displacement at the allylic site.
11 Anions derived from 1,3-dicarbonyls substituted at the C-2 position are found to induce a complete reversal in the mode of ring closure.
12 The major products obtained are 3-[(phenylsulfonyl)methyl]-substituted cyclopentenones. The internal displacement reaction leading to the furan ring apparently encounters an unfavorable A
1,3-interaction in the transition state when a substituent group is present at the 2-position of the dicarbonyl compound. This steric interaction is not present in the transition state leading to the cyclopentenone ring.
Since DBP can react with a variety of β-dicarbonyl anions, a wide assortment of furans and cyclopentenones is available. In addition to its ease of removal,
13 the pendant sulfone also offers a convenient and versatile site for further elaboration (via alkylation
14 or Julia coupling
15). This strategy toward furans and cyclopentenones can clearly be applied to more complex targets.
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
brine
Benzene, [(2,3-dibromo-1-propenyl)sulfonyl]-, Furan, 2-methyl-4-[(phenylsulfonyl)methyl]-, and 2-Cyclopenten-1-one, 2-methyl-3-[(phenylsulfonyl)methyl]-
2,3-dibromo-1-(phenylsulfonyl)-1,2-propene (DBP)
acetic acid (64-19-7)
ethyl acetate (141-78-6)
methanol (67-56-1)
ether (60-29-7)
ammonium chloride (12125-02-9)
sodium bicarbonate (144-55-8)
bromine (7726-95-6)
sodium thiosulfate (7772-98-7)
nitrogen (7727-37-9)
sodium methoxide (124-41-4)
carbon (7782-42-5)
sodium (13966-32-0)
hydrogen peroxide (7722-84-1)
dichloromethane (75-09-2)
magnesium sulfate (7487-88-9)
2,4-pentanedione (123-54-6)
hexane (110-54-3)
triethylamine (121-44-8)
calcium hydride (7789-78-8)
propargyl alcohol (107-19-7)
Phenylsulfenyl chloride (931-59-9)
3-methyl-2,4-pentanedione (815-57-6)
silver tetrafluoroborate (14104-20-2)
2,3-Dibromo-1-(phenylsulfonyl)-1-propene (132604-65-0)
2-METHYL-4-[(PHENYL-SULFONYL)METHYL]FURAN,
2-Methyl-4-[(phenylsulfonyl)methyl]furan (128496-98-0)
2-METHYL-3-[(PHENYLSULFONYL)METHYL]-2-CYCLOPENTEN-1-ONE
1-(Phenylsulfonyl)-1,2-propadiene (2525-42-0)
magnesium-iodine
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