1,3-Benzodithiol-1-ium Tetrafluoroborate1

[57842-27-0]  · C7H5BF4S2  · 1,3-Benzodithiol-1-ium Tetrafluoroborate  · (MW 240.07)

(formyl2 and methyl cation3 equivalent; nucleoside hydroxyl protection group;4 1,1-dipole equivalent11)

Physical Data: mp 150-150.5 °C (dec).

Solubility: sol MeCN and DMF (slowly reacts); insol ether.

Form Supplied in: light brown powder.

Preparative Method: treatment of 2-(3-methylbutoxy)-1,3-benzodithiole2 with Tetrafluoroboric Acid in Acetic Anhydride at 0 °C.

Purification: recrystallized from acetic acid or acetonitrile/ether.

Handling, Storage, and Precautions: can be stored in the absence of moisture and light; no toxicity data is currently available; 1,3-benzodithiol-1-ium perchlorate [32283-21-9] is also known,2 but poses a risk of explosion.

Acyl Cation Equivalent.

Benzodithiolium ions react with a wide range of carbon nucleophiles to afford masked aldehyde and ketone products.2 Electron-rich arenes (eq 1)5 and active methylene compounds6 are useful nucleophiles and 2-substituted benzodithiolium ions lead to good yields of 1-deuteroaldehydes upon reaction with LiAlD4 and subsequent hydrolysis.7

Ketone products are available by a reaction sequence involving Grignard reagent addition to the parent cation followed by regeneration of the 2-substituted 1,3-benzodithiolium ion via Triphenylmethyl Perchlorate mediated hydride abstraction. A second Grignard reagent addition and dithiole hydrolysis completes the sequence (eq 2).8 Chloramine-T in conjunction with Mercury(II) Chloride is a superior method for benzodithiole hydrolysis.7,8a Reductive cleavage of the benzodithiole unit can be achieved by treatment with Sodium-Ammonia.8

Methyl Cation Equivalent.

Mild N-methylation of guanosine has been achieved employing 1,3-benzodithiol-1-ium tetrafluoroborate as a masked methyl group. Treatment of the O-silylated guanosine derivative (2) with (1a) provided high yields of (3), which on exposure to Tri-n-butylstannane provided the N-methyl compound (4) (eq 3).3 This process can be repeated to afford the corresponding N,N-dimethyl derivative. A related O-methylation sequence is not as effective.3,9

Nucleoside Hydroxyl Group Protection.

The benzodithiole group has been used as a selective protecting group for the 5-hydroxyl group of thymidine (eq 4).4 No competitive reactions with base residues were noted with any of the nucleosides studied. The benzodithiole protection can be cleaved to reveal the free hydroxyl group with 2% aqueous TFA.

1,1-Dipole Equivalents.

The parent 1,3-benzodithiole species can be rendered nucleophilic by deprotonation at the 2-position with strong base. A useful reagent for expressing this nucleophilic character is readily available 2-diethoxyphosphinyl-1,3-benzodithiole.10 Reaction of the 2-lithiated species (5) with aldehydes affords excellent yields of ketene dithioacetals suitable for accessing the corresponding substituted benzodithiolium cations for subsequent carbon-carbon bond formation (eq 5).11

See also 2-(3-Methylbutoxy)-1,3-benzodithiolane.

1. (a) Nakayama, J. Sulfur Rep. 1985, 4, 159. (b) Lozac'h, N.; Stavaux, M. in Advances in Heterocyclic Chemistry; Katritzky, A. R.; Boulton, A. J.; Eds.; Academic Press: New York, 1980; Vol. 27, p 151.
2. (a) Nakayama, J.; Fujiwara, K.; Hoshino, M. BCJ 1976, 49, 3567. (b) Nakayama, J. S 1975, 38.
3. Sekine, M.; Satoh, T. JOC 1991, 56, 1224.
4. Sekine, M.; Hata, T. JACS 1983, 105, 2044.
5. Nakayama, J. S 1975, 170.
6. (a) Nakayama, J. JCS(P1) 1976, 540. (b) Scherowsky, G.; Weiland, J. LA 1974, 403.
7. Degani, I.; Fochi, R. S 1976, 759.
8. (a) Degani, I.; Fochi, R. JCS(P1) 1976, 1886. (b) Degani, I.; Fochi, R. S 1976, 471.
9. Sekine, M.; Nakanishi, T. JOC 1990, 55, 924.
10. Akiba, K.; Ishikawa, K.; Inamoto, N. BCJ 1978, 51, 2674.
11. (a) Rigby, J. H.; Kotnis, A.; Kramer, J. JOC 1990, 55, 5078. (b) Rigby, J. H.; Kotnis, A. S. TL 1987, 28, 4943.

James H. Rigby

Wayne State University, Detroit, MI, USA

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