3-(2-Benzyloxyacetyl)thiazolidine-2-thione1

[92486-00-5]  · C12H13NO2S2  · 3-(2-Benzyloxyacetyl)thiazolidine-2-thione  · (MW 267.36)

(synthon for a-benzyloxy carboxylic esters, amides, or aldehydes;2,3 enolate precursor for the diastereo- and enantioselective aldol reactions4)

Physical Data: mp 81.0-82.0 °C.

Form Supplied in: slightly yellow crystals

Preparative Method: methyl 2-hydroxyacetate is converted to methyl 2-benzyloxyacetate (1, NaH; 2, BnBr, DMF, 0 °C to rt, 80%). The acetate is then treated with LiOH.H2O (1.25 equiv) in THF-H2O at rt to give 2-benzyloxyacetic acid (99%). The acid is converted to the corresponding acid chloride (oxalyl chloride (2.7 equiv, 60 °C, 1.5 h), which is treated with thiazolidine-2-thione in the presence of triethylamine in dichloromethane to give the title reagent (1) (81% from the acid).

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

Diastereo- and Enantioselective Aldol Reactions.

Optically active 1,2-diol units are widely distributed in natural products such as macrolides, polyethers, and carbohydrates, etc. The aldol reactions of the enolates derived from a-alkoxyacetic acid ester derivatives with aldehydes provide a useful way to construct 1,2-diols,5 and several asymmetric reactions have been developed.

The tin(II) enolate prepared from (1), Tin(II) Trifluoromethanesulfonate, and 1-Ethylpiperidine reacts with aldehydes in the presence of N,N,N,N-Tetramethylethylenediamine (TMEDA) to afford the anti aldol adducts in good yields with good selectivities (eq 1). Interestingly, syn selective reactions proceed in the absence of TMEDA. Optically active anti aldol adducts can be obtained in the presence of chiral diamine (2) instead of TMEDA.

The tin(II) enolate of chiral oxazolidinone derivative (3) also works well in the presence of TMEDA to give the anti aldol in good yield.6

Optically active syn and anti diol units can be easily prepared by the asymmetric aldol reaction of aldehydes with silyl enolates (4) and (5), respectively, under the influence of chiral tin(II) Lewis acid (6).7,8 Diastereofacial selectivities are controlled simply by choosing the protective group of the a-alkoxy part of ketene silyl acetals (eqs 2 and 3).

While stoichiometric amounts of chiral sources are required in the reaction of eqs 2 and 3, the truly catalytic asymmetric version is realized by using a novel catalyst system consisting of tin(II) triflate, chiral diamine (7), and tin(II) oxide (eq 4).9

Related Reagents.

Ethyl Mandelate; Phenoxyacetic Acid.


1. (a) Mukaiyama, T. PAC 1983, 55, 1749. (b) Mukaiyama, T. Isr. J. Chem. 1984, 24, 162. (c) Mukaiyama, T. Chem. Scr. 1985, 25, 13. (d) Mukaiyama, T.; Asami, M. Top. Curr. Chem. 1985, 127, 133. (e) Mukaiyama, T. PAC 1986, 58, 505.
2. (a) Izawa, T.; Mukaiyama, T. CL 1977, 1443. (b) Izawa, T.; Mukaiyama, T. BCJ 1979, 52, 555.
3. (a) Mukaiyama, T.; Iwasawa, N. CL 1982, 1903. (b) Mukaiyama, T.; Iwasawa, N.; Stevens, R. W.; Haga, T. T 1984, 40, 1381.
4. Mukaiyama, T.; Iwasawa, N. CL 1984, 753.
5. (a) Touzin, A. M. TL 1975, 1477. (b) Heathcock, C. H.; Hagan, J. P.; Jarvi, E. T.; Pirrung, M. C.; Young, S. D. JACS 1981, 103, 4972.
6. Evans, D. A.; Gage, J. R.; Leighton, J. L.; Kim, A. S. JOC 1992, 57, 1961.
7. Mukaiyama, T.; Uchiro, H.; Shiina, I.; Kobayashi, S. CL 1990, 1019.
8. Mukaiyama, T.; Shiina, I.; Kobayashi, S. CL 1991, 1901.
9. Kobayashi, S.; Kawasuji, T. SL 1993, 911.

Shū Kobayashi

Science University of Tokyo, Japan



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