2-(S)-[(4-Methylphenyl)sulfinyl]-2-cyclopenten-1-one (Ar = Tol), 2-(S)-[(4-Methoxyphenyl)sulfinyl]-2-cyclopenten-1-one (Ar = p-anisyl), 2-(S)-(1-Naphthylsulfinyl)-2-cyclopenten-1-one (Ar = 1-naphthyl), 2-(S)-[(2,4,6-Trimethylphenyl)sulfinyl]-2-cyclopenten-1-one (Ar = 2,4,6-trimethylphenyl), 2-(S)-[(2,4,6-Triisopropylphenyl)sulfinyl]-2-cyclopenten-1-one (Ar = 2,4,6-triisopropylphenyl)

[79681-26-8], [93366-59-7], [82136-10-5], [178670-85-4], [151951-76-7]  · C12H12O2S, C12H12O3S, C15H12O2S, C14H16O2S, C20H28O2S  · (MW 220.29), (MW 236.29), (MW 256.32), (MW 248.34), (MW 332.49)

(useful intermediates in the synthesis of chiral cyclic compounds)

Physical Data: Ar = Tol,1 mp 125-126 °C; [a]D25 + 148° (c 0.11, CHCl3). Ar = p-anisyl,2 mp 120.5-121.5 °C; [a]D25 + 141° (c 1.45, acetone). Ar = 1-naphthyl,3 mp 96.5-97.0 °C; [a]D25 + 291.5° (c 1.30, acetone). Ar = 2,4,6-trimethylphenyl,4 mp 131.6-132.0 °C; [a]D20 + 354.5° (c 0.416, CHCl3). Ar = 2,4,6-triisopropylphenyl,4 mp 139.5-140.4 °C; [a]D17 + 229.2° (c 0.216, CHCl3).

Analysis of Reagent Purity: Ar = Tol, IR (CCl4) cm-1: 1715, 1H NMR (CDCl3) d 2.2-2.5 (m, 2H), 2.30 (s, 3H), 2.6-2.8 (m, 2H) 7.19 and 7.58 (2d, 4H), 8.03 (t, 1H).

Preparative Methods: prepared from 2-bromo-2-cyclopenten-1-one in three steps (1),1 involving a key reaction of the vinyllithium and (S)-menthyl p-toluenesulfinate which proceeds with complete inversion at sulfur.5

Handling, Storage, and Precautions: 2-(S)-[(4-methylphenyl)sulfinyl]-2-cyclopenten-1-one can be stored in vials in a desiccator at 0 °C for more than 1 year without decomposition. It became discolored after several weeks when exposed to the atmosphere at room temperature.

Michael Additions

The title compound 2-(S)-[(4-methylphenyl)sulfinyl]-2-cyclopenten-1-one (1) gives the conjugate addition products with excellent stereoselectivity (2).6 1 is either treated directly with Grignard reagents or first treated with ZnBr2 and subsequently with Grignard reagents to give, after reductive removal of the sulfinyl group, (R)-3-substituted cyclopentanones in excellent enantiomeric purity (1).3,7 The (R)-3-substituted cyclopentanones are formed through a chelated intermediate 2. On the other hand, the conjugate addition with MeMgI or R2Mg occurs from the diastereotopic face opposite to the bulky p-tolyl group in conformation 3 having the sulfoxide and carbonyl dipoles oriented in opposite directions, to give (S)-3-substituted cyclopentanones (1).8 Replacing the p-tolyl to the p-anisyl group, which would stabilize the chelate more effectively, causes a noticeable increase in diastereoselectivity (1).2,9 The reaction of the cyclopentenone having the bulky 1-naphthylsulfinyl group with Me2CuLi gives the (S)-product in 57% ee (1).7a

The conjugate addition with a naphthyl group affords the addition product. Methylation, reductive cleavage of the sulfinyl group, and alkylation give the optically pure steroid intermediate (3).3

Reagent 1 also undergoes asymmetric Michael additions with enolate ions.10 Michael additions with disubstituted lithium enolates proceed with almost complete p-facial diastereoselectivity. Starting with these Michael additions, (-)-methyl jasmonate11 (4) and (-)-estrone methyl ether12 (5) can be obtained in high enantiomeric purities.

The TiCl4-catalyzed reaction of 1 with crotylsilanes proceeds with high diastereoselectivity to give the (3S)-products (6).13 Reaction of 2-(phenylsulfinyl)-2-cyclopenten-1-one with LiOO-t-Bu gives the epoxide with low diastereoselectivity.14

Diels-Alder Reactions

Reagent 1 is useful as an efficient chiral dienophile in asymmetric Diels-Alder reactions. Reaction of 1 with cyclopentadiene in the presence of a Lewis acid occurs with high stereoselectivity.15 Reaction with 6-methoxy-1-vinyl-3,4-dihydronaphthalene in the presence of EtAlCl2 proceeds with complete regioselectivity and endo selectivity (7).16 This stereochemical result can be explained in terms of a chelated conformer which directs the stereochemistry of approach of the dienophile.

Treatment of 2-(phenylsulfinyl)-2-cyclopenten-1-one with phthalic anhydride in the presence of NaH gives the [4 + 2] cycloaddition product (8).17

Reaction with Alkyl Radicals

The addition of alkyl radicals to 1 affords the products in good yields but with low stereoselectivity (9). In order to shield one diastereotopic face effectively toward the attack of alkyl radicals, the cyclopentenone should have a sterically bulkier aryl group on the sulfur, i.e. the sulfoxides having an ortho-substituted aryl group show high diastereoselection. Thus, 2-(S)-[(2,4,6-triisopropylphenyl)sulfinyl]-2-cyclopenten-1-one (4) and 2-(S)-[(2,4,6-trimethylphenyl)sulfinyl]-2-cyclopenten-1-one (5) give (R)-3-alkylated cyclopentanones with extremely high diastereoselectivities in reactions with alkyl radicals such as a t-butyl, isopropyl, or cyclohexyl radical, and even with the less bulky ethyl radical (2).4,18 The reaction of 5 with a tert-butyl radical in the presence of EtAlCl2 or TiCl2(O-i-Pr)2 completely reverses the face selection, giving only the (3S)-3-tert-butylcyclopentanone (2). The change in the product distribution is apparently due to the conformation fixed by chelation with a Lewis acid between the carbonyl and sulfinyl oxygens. However, ZnBr2, which is an efficient chelating Lewis acid in the Michael additions, causes only a small change or none in the product ratio in these radical reactions.

The photo-induced reaction of 2-sulfinylcyclopentenones in alcohols in the presence of Ph2CO gives addition products (10). Reagent 1 shows low stereoselectivity, whereas complete diastereoselection can be achieved in the reaction of 4 and 5 (3).19


1. Hulce, M.; Mallomo, J. P.; Frye, L. L.; Kogan, T. P.; Posner, G. H., Org. Synth., Coll. Vol. 1990, 7, 495.
2. Posner, G. H.; Frye, L. L.; Hulce, M., Tetrahedron 1984, 40, 1401.
3. Posner, G. H.; Mallamo, J. P.; Hulce, M.; Frye, L. L., J. Am. Chem. Soc. 1982, 104, 4180.
4. Mase, N.; Watanabe, Y.; Ueno, Y.; Toru, T., J. Org. Chem. 1997, 62, 7794.
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6. Posner, G. H., Acc. Chem. Res. 1987, 20, 72.
7. (a) Posner, G. H.; Mallamo, J. P.; Miura, K., J. Am. Chem. Soc. 1981, 103, 2886. (b) Posner, G. H.; Hulce, M.; Mallamo, J. P.; Drexler, S. A.; Clardy, J., J. Org. Chem. 1981, 46, 5244. (c) Posner, G. H., In Asymmetric Synthesis; Morrison, J. D., Ed.: Academic: New York, 1983, Vol. 2, p 239.
8. Posner, G. H.; Hulce, M., Tetrahedron Lett. 1984, 25, 379.
9. Posner, G. H.; Frye, L. L., Isr. J. Chem. 1984, 24, 88.
10. (a) Posner, G. H.; Wayne, H., J. Chem. Soc., Chem. Commun. 1985, 1786. (b) Posner, G. H.; Weitzberg, M.; Hamill, T. G.; Asirvatham, E., Tetrahedron 1986, 42, 2919. (c) Posner, G. H.; Weitzberg, M.; Jew, S. S., Synth. Commun. 1987, 17, 611.
11. (a) Posner, G. H.; Asirvatham, E., J. Org. Chem. 1985, 50, 2589. (b) Posner, G. H.; Asirvatham, E.; Ali, S. F., J. Chem. Soc., Chem. Commun. 1985, 542.
12. Posner, G. H.; Switzer, C., J. Am. Chem. Soc. 1986, 108, 1239.
13. Pan, L. R.; Tokoroyama, T., Tetrahedron Lett. 1992, 33, 1469.
14. Fernandez de la Pradilla, R.; Castro, S.; Manzano, P.; Martin-Ortega, M.; Priego, J.; Viso, A.; Rodriguez, A.; Fonseca, I., J. Org. Chem. 1998, 63, 4954.
15. Alonso, I.; Carretero, J. C.; Garcia Ruano, J. L., Tetrahedron Lett. 1989, 30, 3853.
16. Alonso, I.; Carretero, J. C.; Garcia Ruano, J. L.; Martin Cabrejas, L. M., Tetrahedron Lett. 1994, 35, 9461.
17. Fujioka, H.; Akai, S.; Kita, Y., J. Org. Chem. 2000, 65, 89.
18. (a) Toru, T.; Watanabe, Y.; Tsusaka, M.; Ueno, Y., J. Am. Chem. Soc. 1993, 113, 19464. (b) Toru, T.; Watanabe, Y.; Mase, N.; Tsusaka, M.; Hayakawa, T.; Ueno, Y., Pure Appl. Chem. 1996, 68, 711.
19. Mase, N.; Watanabe, Y.; Toru, T., Bull. Chem. Soc. Jpn. 1998, 71, 2957.

Takeshi Toru

Nagoya Institute of Technology, Nagoya, Japan



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