Trimethylene Oxide

[503-30-0]  · C3H6O  · Trimethylene Oxide  · (MW 58.09)

(three-carbon homologation)

Alternate Name: oxetane.

Physical Data: bp 50 °C; d 0.893 g cm-3.

Solubility: sol H2O and most common organic solvents.

Form Supplied in: commercially available in 97% purity.

Preparative Methods: from 3-chloropropyl acetate and Potassium Hydroxide;1 from 1,3-Propanediol and Diethyl Azodicarboxylate/Triphenylphosphine.2

Purification: by distillation.

Reaction with Carbon Nucleophiles.

Trimethylene oxide readily undergoes ring opening with a variety of carbon nucleophiles to give the three-carbon homologated alcohol. Substituted oxetanes undergo analogous reactions. Grignard reagents and alkyllithiums react cleanly, although reduced yields are obtained with secondary Grignard reagents (eq 1).3 Alkyl cuprates,4 alkenyllithium,5 alkenylaluminum,6 alkynyllithium,7 and allyllithium8 reagents have been used to open oxetane. Reaction with ester and amide enolates provides access to 5-hydroxy esters and amides (eq 2)9 and ketone imine salts react with oxetane (eq 3) as well.10 Boron Trifluoride Etherate is frequently used to assist the ring opening. Oxetane reacts with allylsilanes and Titanium(IV) Chloride to give the ring-opened products (eq 4).11

Reaction with Heteroatom Nucleophiles.

Trimethylene oxide undergoes ring opening with a wide variety of heteroatom nucleophiles. Reaction with Cyanotrimethylsilane gives, after hydrolysis of the isocyanide, 3-aminopropanol (eq 5).12,13 3-Hydroxydimethylsulfonium salts are obtained on reaction with Trifluoromethanesulfonic Acid and Dimethyl Sulfide.14 Phosphonium salts are obtained on reaction with Triphenylphosphine and Trifluoroacetic Acid or triflic acid (eq 6).15 Reaction with phosphine anions gives the 3-hydroxypropylphosphines.16 Trimethylene oxide is readily opened by selenium nucleophiles, such as phenylselenide anion, which gives 3-hydroxypropyl phenyl selenide.17

Reductive Opening of Oxetane.

Reduction with Lithium 4,4-Di-t-butylbiphenylide (LDDB) gives the 3-lithioalkoxide, which reacts with a wide variety of electrophiles (eq 7).18 A similar opening occurs with the Potassium/18-Crown-6 complex.19

1. Noller, C. R. OSC 1955, 3, 835.
2. Carlock, J. T.; Mavk, M. P. TL 1978, 5153.
3. Searles, S. JACS 1951, 73, 123.
4. Millon, J.; Linstrumelle, G. TL 1976, 1095.
5. Overman, L. E.; Thompson, A. S. JACS 1988, 110, 2248.
6. Alexakis, A.; Jachiet, D. T 1989, 45, 6197.
7. Yamaguchi, M.; Nobayashi, Y.; Hirao, I. TL 1983, 24, 5121.
8. Yamaguchi, M.; Shibato, K.; Hirao, I. TL 1984, 25, 1159.
9. Fang, J.-M.; Chen, M.-Y. TL 1988, 29, 5939.
10. Hudrlik, P. F.; Wan, C.-N. JOC 1975, 40, 2963.
11. Carr, S. A.; Weber, W. P. JOC 1985, 50, 2782.
12. Gassman, P. G.; Haberman, L. M. TL 1985, 26, 4971.
13. Carr, S. A.; Weber, W. P. SC 1985, 15, 775.
14. Okuma, K.; Nakamura, S.; Ohta, H. H 1987, 26, 2343.
15. Yamamoto, S.; Okuma, K.; Ohta, H. BCJ 1988, 61, 4476.
16. Tsvetkov, E. N.; Bondarenko, N. A.; Malakhova, I. G.; Kabachnik, M. I. S 1986, 198.
17. (a) Haraguchi, K.; Tanaka, H.; Hayakawa, H.; Miyasaka, T. CL 1988, 931. (b) Haraguchi, K.; Tanaka, H.; Miyasaka, T. S 1989, 434. (c) Miyoshi, N.; Hatayama, Y.; Ryu, I.; Kambe, N.; Murai, T.; Murai, S.; Sonoda, N. S 1988, 175. (d) Sukata, K. BCJ 1990, 63, 825.
18. (a) Mudryk, B.; Cohen, T. JOC 1989, 54, 5657. (b) Mudryk, B.; Cohen, T. JACS 1993, 115, 3856. (c) Licandro, E.; Maiorana, S.; Papagni, A.; Zanotti-Gerosa, A. CC 1992, 1623.
19. Jedlinski, A.; Misiolek, A.; Jankowski, A.; Janeczek, H. CC 1991, 1513.

Kevin E. Henegar

The Upjohn Company, Kalamazoo, MI, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.