Bis(methylthio)(trimethylsilyl)methane

[37891-79-5]  · C6H16S2Si  · Bis(methylthio)(trimethylsilyl)methane  · (MW 180.40)

(reagent used for synthesis of bis(methylthio)ketene acetals from aldehydes and ketones;1 acyl anion synthon for conjugate additions to enones and enoates;2 useful for one-carbon homologations3)

Physical Data: bp 67-70 °C/10 mmHg.

Solubility: insol H2O; sol organic solvents.

Preparative Methods: prepared from lithiobis(methylthio)methane by silylation with chlorotrimethylsilane (eq 1).1 Both bis(methylthio)methane and Chlorotrimethylsilane are commercially available.

Handling, Storage, and Precautions: use in a fume hood.

Lithiobis(methylthio)(trimethylsilyl)methane.

The anion is generated by treatment of the title compound with n-Butyllithium in THF at -60 °C (eq 2). This species is well-behaved at low temperature. Useful reactions of this anion are discussed in the following sections.

Thioketene Acetals.

The lithio reagent readily converts aldehydes and ketones into the corresponding bis(methylthio)ketene acetals via a Peterson alkenation sequence.1 Aromatic aldehydes give excellent yields under these conditions (eq 3), and certain enolizable ketones such as acetophenone and cyclohexanone also react accordingly (eq 4). Alternative methods for preparing these acetals include a Horner-Wittig process that uses phosphonate derivatives4 and an alkylative process involving CS2 and MeI.5 Relative to these alternatives, the title reagent offers advantages of ease of reagent preparation and control of regioselectivity. The phosphonate reagents are more nucleophilic, however, and avoid competitive deprotonation.

Reaction of the lithio species with a-oxo ketones and aldehydes allows the formation of b,b-disubstituted enones, useful intermediates for the preparation of unsaturated 1,5-diketones (eq 5).6

Acyl Anion Conjugate Additions.

The lithio reagent readily undergoes 1,4-addition to unsaturated substrates (eq 6), in direct contrast to the corresponding RL031-, which is a poor Michael donor.2 The initial Michael adducts can also be alkylated to provide highly functionalized products. Very good levels of diastereoselectivity have been observed in the 1,4-addition and enolate alkylations of cyclic enoates (eq 7)7 and acyclic enones (eq 8).8

Other effective Michael donors of this type include lithiobis(phenylthio)(trimethylsilyl)methane,9 lithio(methoxy)(phenylthio)(trimethylsilyl)methane,10 and lithio(methylthio)(methylsulfoxido)methane.11 The isolated yields with lithiobis(phenylthio)(trimethylsilyl)methane are generally superior to those with the title reagent, but the latter compound is more readily available and easier to handle than those listed above.

One-Carbon Homologations.3

The bis(methylthio)ketene acetals are useful synthetic intermediates because they are readily converted into S-methyl thioesters (eq 9)12 or the corresponding carboxylic acids and esters.13a

This acetal methodology was used for a 1,3-carbonyl transposition in a synthesis of (±)-myodesmone (eq 10),13b and for a one-carbon homologation en route to vitamin B12 (eq 11).14

A particularly useful transformation is the fluoride-induced removal of the trimethylsilyl group to provide a mixed O,S-acetal that is easily converted into the corresponding aldehyde (eq 12).10


1. Seebach, D.; Kolb, M.; Gröbel, B.-T. CB 1973, 106, 2277.
2. Seebach, D.; Bürstinghaus, R. AG(E) 1975, 14, 57.
3. Martin, S. F. S 1979, 633.
4. (a) Mikolajczyk, M.; Grzejszczak, S.; Zatorski, A. TL 1976, 17, 2731. (b) Kruse, C. G.; Broekhof, N. L. J. M.; Wijsman, A.; van der Gen, A. TL 1977, 18, 885.
5. Potts, K. T.; Cipullo, M. J.; Ralli, P.; Theodoridis, G. JOC 1982, 47, 3027.
6. Potts, K. T.; Cipullo, M. J.; Ralli, P.; Theodoridis, G. JACS 1981, 103, 3584.
7. Tomioka, K.; Kawasaki, H.; Yasuda, K.; Koga, K. JACS 1988, 110, 3597.
8. Kawasaki, H.; Tomioka, K.; Koga, K. TL 1985, 26, 3031.
9. Myers, M. R.; Cohen, T. JOC 1989, 54, 1290.
10. Otera, J.; Niibo, Y.; Nozaki, H. JOC 1989, 54, 5003.
11. Ogura, K.; Yamashita, M.; Tsuchihashi, G.-I. TL 1978, 19, 1303.
12. Seebach, D.; Bürstinghaus, R. S 1975, 461.
13. (a) Myrboh, B.; Ila, H.; Junjappa, H. JOC 1983, 48, 5327. (b) Dieter, R. K.; Lin, Y. J.; Dieter, J. W. JOC 1984, 49, 3183.
14. Stevens, R. V.; Chang, J. H.; Lapalme, R.; Schow, S.; Schlageter, M. G.; Shapiro, R.; Weller, H. N. JACS 1983, 105, 7719.

John W. Benbow

Lehigh University, Bethlehem, PA, USA



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