3-Propionylthiazolidine-2-thione1

[85260-51-1]  · C6H9NOS2  · 3-Propionylthiazolidine-2-thione  · (MW 175.30)

(synthesis of b-hydroxy-a-methyl carboxylic esters, amides, and aldehydes,2 propionate equivalent for the diastereo- and enantioselective aldol reactions2,3)

Physical Data: bp 151 °C/4 mmHg.

Form Supplied in: sticky, slightly yellow oil.

Preparative Methods: from propionyl chloride and 1,3-Thiazolidine-2-thione in the presence of Triethylamine, or from Propionic Acid and thiazolidine-2-thione in the presence of triethylamine and 2-Chloro-1-methylpyridinium Iodide.4

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

Diastereoselective Aldol Reactions.

The tin(II) enolate generated from 3-propionylthiazolidine-2-thione (1), Tin(II) Trifluoromethanesulfonate, and 1-Ethylpiperidine reacts with aldehydes at -78 °C to afford the aldol adducts in high yields with high syn selectivities (eq 1).2,3 3-Acetylthiazolidine-2-thione (2) (bp 125-128 °C/2 mmHg)2,3,5,8 and 3-(3-phenylpropanoyl)thiazolidine-2-thione (3) (mp 66.0-67.5 °C)2-4 also work well under the same reaction conditions.2,3

The aldol adducts (4) are easily converted to the corresponding b-hydroxy-a-methyl esters, amides, and aldehydes. Treatment of (4) (R = Ph) with methanol or ethanol in the presence of Potassium Carbonate at room temperature gives the methyl or ethyl ester in high yield (eq 2).2 Similarly, the amide is spontaneously formed by mixing (4) with the amine in dichloromethane (eq 3).2 The preparation of the aldehyde is carried out by using Diisobutylaluminum Hydride as a reductant after protection of the hydroxy function of (4) with the dimethylisopropylsilyl group (eq 4).2,4 No isomerization occurs during these conversions.

Enantioselective Aldol Reactions.

A highly enantioselective aldol reaction of the tin(II) enolate derived from (2) with aldehydes is carried out in the presence of the chiral diamine (5) as a ligand (eq 5).3,5,6 Aromatic and aliphatic ketones instead of (2) are good substrates in the present asymmetric aldol reaction,3,7 and enantioselectivities are influenced strongly by the structure of the chiral diamines.

The tin(II) enolate of (2) reacts with a-keto esters in the presence of the chiral diamine (6) to give optically active 2-substituted malic acid ester derivatives in high yields with high ee (eq 6).8

The tin(II) enolate of (2) also reacts with chiral aldehydes in the presence of (5). Diastereoselectivities can be controlled by the absolute configuration of the chiral diamines (eqs 7 and 8).1f

In the reaction of the tin(II) enolate derived from (1) with aldehydes, enantioselectivities are disappointingly low, while good diastereoselectivities are observed. Highly diastereo- and enantioselective aldol reactions of propionate derivatives with aldehydes have been achieved by using the ketene silyl thioacetal (7) instead of the tin(II) enolate. The complex (8) produced by mixing tin(II) triflate and the chiral diamine (6) works as an efficient chiral Lewis acid. The reaction of (7) with various aldehydes proceeds smoothly in the presence of (8) and dibutyltin diacetate in dichloromethane to afford the syn aldol adducts in high yields with almost perfect stereochemical control (eq 9).9

While stoichiometric amounts of tin(II) triflate, (6), and the tin(IV) compound are necessary in the reaction shown in eq 9, the truly catalytic asymmetric aldol reaction of (7) with aldehydes is realized by using (8) as a Lewis acid catalyst (eq 10).10 The reaction is carried out in propionitrile by slow addition of the substrates to the catalyst.

Related Reagents.

3-(2-Benzyloxyacetyl)thiazolidine-2-thione; 2,6-Dimethylphenyl Propionate; 2-Methyl-2-(trimethylsilyloxy)-3-pentanone; 1,3-Thiazolidine-2-thione; Tin(II) Trifluoromethanesulfonate.


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. (f) Mukaiyama, T. Challenges in Synthetic Organic Chemistry; Oxford University Press: Oxford, 1990; p 191.
2. Mukaiyama, T.; Iwasawa, N. CL 1982, 1903.
3. Mukaiyama, T.; Iwasawa, N.; Stevens, R. W.; Haga, T. T 1984, 40, 1381.
4. (a) Izawa, T.; Mukaiyama, T. CL 1977, 1443. (b) Izawa, T.; Mukaiyama, T. BCJ 1979, 52, 555.
5. Iwasawa, N.; Mukaiyama, T. CL 1983, 297.
6. (a) Asami, M.; Ohno, H.; Kobayashi, S.; Mukaiyama, T. BCJ 1978, 51, 1869. (b) Mukaiyama, T. T 1981, 37, 4111.
7. Iwasawa, N.; Mukaiyama, T. CL 1982, 1441.
8. Stevens, R. W.; Mukaiyama, T. CL 1983, 1799.
9. (a) Kobayashi, S.; Uchiro, H.; Fujishita, Y.; Shiina, I.; Mukaiyama, T. JACS 1991, 113, 4247. (b) Mukaiyama, T.; Uchiro, H.; Kobayashi, S. CL 1989, 1001. (c) Mukaiyama, T.; Uchiro, H.; Kobayashi, S. CL 1989, 1757.
10. (a) Kobayashi, S.; Uchiro, H.; Shiina, I.; Mukaiyama, T. T 1993, 49, 1761. (b) Mukaiyama, T.; Kobayashi, S.; Uchiro, H.; Shiina, I. CL 1990, 129. (c) Kobayashi, S.; Fujishita, Y.; Mukaiyama, T. CL 1990, 1455.

Shū Kobayashi

Science University of Tokyo, Japan



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