1,3-Dithiane1

[505-23-7]  · C4H8S2  · 1,3-Dithiane  · (MW 120.26)

(functional group equivalent; umpolung; C-C bond formation)

Physical Data: mp 53-54 °C; fp 90 °C; bp 207-208 °C/760 mmHg, 60-62 °C/12 mmHg.

Solubility: very sol C6H6, ether, CHCl3, THF; slightly sol H2O.

Form Supplied in: slightly yellow needles; hygroscopic.

Analysis of Reagent Purity: mp, as well as by visual inspection; freshly sublimed reagent is snow white.

Purification: sublimes 45-48 °C (bath temp)/0.1-0.5 mmHg; recryst MeOH (0.5 g mL-1).

Handling, Storage, and Precautions: IPR-MUS LD50: 1500 mg/kg; RTECS No. J05070000. May be harmful by inhalation, ingestion, or skin absorption; may cause irritation; exposure can cause nausea, headache, and vomiting; toxicological properties have not been thoroughly investigated. Stench! Use in a well ventilated fume hood.

Synthesis of 1,3-Dithianes.

The standard procedure to prepare 1,3-dithianes involves the Lewis-acid catalyzed derivatization of aldehydes or acetals with 1,3-Propanedithiol1c,2-4 or with a derivative of the dithiol with an oxophile.5,6 The use of ketones,3 acids,7 or methyl ethers8 as starting material has been reported. As an alternative, the thioacetal formation can be initiated by a Brønsted acid, e.g. the clay montmorillonite KSF.9 Also, the reaction of 1,3-propanedithiol with gem-diiodoalkanes catalyzed by Ph2PCH2PPh2/Pt2+ gives access to 1,3-dithianes,10 as does a double Michael addition reaction sequence on 2-ynone derivatives.11

1,3-Dithianes as Functional Group Equivalents.

R2CO.

The use of the 1,3-dithiane functionality as a protecting group for a ketone or aldehyde (1) has been recognized for some time (Scheme 1).3,4 The good stability of this dithioacetal and its compatibility with a wide variety of reagents are an advantage in this respect. There is a plethora of conditions reported in the literature for unmasking the carbonyl function,1,4,12-14 spanning from oxidative,15 alkylative,16 and photochemical17 to metal-catalyzed procedures.18

R2CH2.

Reduction of 1,3-dithianes to the corresponding alkane (2) is a well-established transformation.14b

R2CF2.

gem-Difluoro compounds (3) can be prepared from ketones and aldehydes via the corresponding 1,3-dithiane in good yield.19 In combination with the potential of 1,3-dithianes for reactivity umpolung, this sequence represents an interesting access to the CF22- synthon.

1,3-Dithianes in Carbon-Carbon Bond Formation.

In addition to the exploitation of its metallated derivative as a versatile reagent for C-C bond formation (see 2-Lithio-1,3-dithiane), 1,3-dithianes have been used in transition metal-catalyzed alkenations to give (4) and gem-dialkylations to yield (5).20 Amino pyridines and anilines can be ortho-formylated on treatment with 1,3-dithiane in the presence of pivaloyl chloride (Trimethylacetyl Chloride) and then base to give (6).21,22 Another option in this category is to use the reagent's cationic counterpart (7), which reacts with enol ethers to give 1,3- or 1,5-dicarbonyl arrangements (see 2-Chloro-1,3-dithiane).23

1,3-Dithianes in Reactivity Umpolung.

The singular most important aspect in 1,3-dithiane chemistry is its use as a carbonyl equivalent which provides umpolung of the normal pattern of reactivity, e.g. acyl anion (8) chemistry.1,24 A comprehensive view of this facet of the 1,3-dithiane reagent is covered under 2-Lithio-1,3-dithiane.

Related Reagents.

Bis(phenylthio)methane; Methoxy(phenylthio)methane.


1. (a) Breslow, D. S.; Skolnik, H. The Chemistry of Heterocyclic Compounds; Interscience: New York, 1966; vol. 21/2, p 979. (b) Fieser, L. F.; Fieser, M. FF 1969, 2, 182; 1972, 3, 135; 1974, 4, 216, 241; 1975, 5, 287, 660; 1977, 6, 119, 248, 677; 1979, 7, 142; 1980, 8, 217, 346; 1981, 9, 48, 308, 309; 1982, 10, 81, 231; 1984, 11, 227, 238, 285, 335; 1986, 12, 573; 1989, 14, 157; 1992, 16, 161. (c) Cook, M. J. In Comprehensive Heterocyclic Chemistry; Katritzky, A.; Rees, C. W., Eds.; Pergamon: Oxford, 1984; vol. 3, p 989. (d) Seebach, D. S 1969, 17. (e) Lever, O. W., Jr. T 1976, 32, 1943. (f) Groebel, B.-T.; Seebach, D. S 1977, 357. (g) ApSimon, J.; Holmes, A. H 1977, 6, 731.
2. Corey, E. J.; Seebach, D. OS 1970, 50, 72.
3. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; Wiley: New York, 1991; p 201.
4. Kunz, H.; Waldmann, H. COS 1991, 6, 679.
5. Sato, T.; Yoshida, E.; Kobayashi, T.; Otera, J.; Nozaki, H. TL 1988, 29, 3971.
6. Soderquist, J. A.; Miranda, E. I. TL 1986, 27, 6305.
7. Kim, S.; Kim, S. S.; Lim, S. T.; Shim, S. C. JOC 1987, 52, 2114.
8. Olah, G. A.; Welch, J. JACS 1978, 100, 5396.
9. Labiad, B.; Villemin, D. SC 1989, 19, 31.
10. Page, P. C. B.; Klair, S. S.; Brown, M. P.; Smith, C. S.; Maginn, S. J.; Mulley, S. T 1992, 48, 5933.
11. Ranu, B. C.; Bhar, S.; Chakraborti, R. JOC 1992, 57, 7349.
12. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; Wiley: New York, 1991; p 203.
13. Boulton, A. J.; McKillop, A. In Comprehensive Heterocyclic Chemistry; Katritzky, A.; Rees, C. W., Eds.; Pergamon: Oxford 1984; Vol. 2, p 63.
14. (a) Larock, C. R. Comprehensive Organic Transformations; VCH: New York, 1989; pp 34, 721.
15. Kiselyov, A. S.; Strekowski, L.; Semenov, V. V. T 1993, 49, 2151.
16. Takano, S.; Hatakeyama, S.; Ogasawara, K. CC 1977, 68.
17. Epling, G. A.; Wang, Q. SL 1992, 335; TL 1992, 33, 5909.
18. Lipshutz, B. H.; Moretti, R.; Crow, R. TL 1989, 30, 15.
19. Sondej, S. C.; Katzenellenbogen, J. A. JOC 1986, 51, 3508.
20. Luh, T.-Y. ACR 1991, 24, 257.
21. Gassmann, P. G.; Huang, C. T. CC 1974, 685.
22. Gassman, P. G.; Drewes, H. R. JACS 1974, 96, 3002.
23. Paterson, I.; Price, L. G. TL 1981, 22, 2829, 2833.
24. Page, P. C. B.; van Niel, M. B.; Prodger, J. C. T 1989, 45, 7643.

Michael Kolb

Marion Merrell Dow, Cincinnati, OH, USA



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