[42075-32-1]  · C5H12O2  · (2R,4R)-2,4-Pentanediol  · (MW 104.17)

(diol used for the preparation of chiral acetals1)

Physical Data: mp 48-50 °C; bp 111-113 °C/19 mmHg.

Form Supplied in: white solid; widely available.

Preparative Methods: via asymmetric hydrogenation of 2,4-Pentanedione.2 Its enantiomer [72345-23-4] is also available by the same method.

Purification: recrystallization from ether.

Handling, Storage, and Precautions: should be stored in a tightly closed container since it is hygroscopic.

Cleavage of Acetals.

Acetals of 2,4-pentanediol are easily prepared from aldehydes via standard procedures (e.g. cat. PPTS, PhH, Dean-Stark removal of H2O). These acetals have been cleaved with a variety of nucleophiles in the presence of Lewis acids to yield hydroxy ethers with high (typically 90-95% de) diastereoselectivities. Oxidation and b-elimination then provides enantiomerically enriched alcohols (eq 1). Nucleophiles have included allylsilanes to produce homoallylic alcohols,3 alkynylsilanes to give propargylic alcohols,4 Me3SiCN to provide (after hydrolysis) a-hydroxy acids,5 and enol silyl ethers, a-silyl ketones, or silyl ketene acetals to yield aldol-type products.6 The same strategy using organometallic reagents/Lewis acid combinations (e.g. RCu/BF3.OEt2,7 RMgX/TiCl4,8 RLi/TiCl4,8,9 R2Zn/TiCl49) is a general route to secondary alcohols. Other nucleophile/Lewis acid combinations that have been used include alkynylstannanes/TiCl410 and zinc enolates/TiCl4.11 These acetals have also been used in polyene cyclizations.3a,12

2,4-Pentanediol is often superior to other diols such as 2,3-butanediol for these reactions because of higher distereoselectivities in reactions with nucleophiles and the more facile cleavage of the resulting hydroxy ether by oxidation-b-elimination.3 Removal of the chiral auxiliary is usually carried out with Pyridinium Chlorochromate oxidation followed by b-elimination using KOH,3 K2CO3,13 piperidinium acetate,6 dibenzylammonium trifluoroacetate,14 or DBU.4c In some cases, 1,3-butanediol is preferred because the final b-elimination may be effected under milder conditions.14

A detailed study of the mechanism and origin of stereoselectivity in reactions of allyltrimethylsilane with dioxane acetals has been published.15

Reduction of Acetals.

Reductions of acetals of 2,4-pentanediol can provide (after removal of the chiral auxiliary by oxidation and b elimination) secondary alcohols with good enantioselectivity. The choice of reagents dictates the configuration of the final product. Use of Dibromoalane gives products from selective syn cleavage of the acetal while Triethylsilane/Titanium(IV) Chloride gives the more usual anti cleavage products (eq 2).13

Elimination of Acetals.

Treatment of 2,4-pentanediol acetals of meso ketones with Triisobutylaluminum gives enol ethers with high diastereoselectivities (eq 3).16

Acetals as Chiral Auxiliaries.

There have been many applications of acetals of 2,4-pentanediol as chiral auxiliaries to control the diastereoselectivity of reactions on another functional group.1 Examples include cyclopropanation of alkenyl dioxanes,17 lithium amide-mediated isomerization of epoxides to allylic alcohols,18 and addition of dioxane-substituted Grignard reagents19 or organolithiums20 to aldehydes.

Other Uses.

Acetals of 2,4-pentanediol have also been prepared in order to determine the enantiomeric purity of aldehydes and ketones by analysis of diastereomers by GC or NMR.21 2,3-Butanediol22 is more commonly used for this purpose but has been shown to be less effective in some cases.

1. Alexakis, A.; Mangeney, P. TA 1990, 1, 477.
2. (a) Ito, K.; Harada, T.; Tai, A. BCJ 1980, 53, 3367. (b) Tai, A.; Kikukawa, T.; Sugimura, T.; Inoue, Y.; Osawa, T.; Fujii, S. CC 1991, 795, 1324.
3. (a) Bartlett, P. A.; Johnson, W. S.; Elliott, J. D. JACS 1983, 105, 2088. (b) Johnson, W. S.; Crackett, P. H.; Elliott, J. D.; Jagodzinski, J. J.; Lindell, S. D.; Natarajan, S. TL 1984, 25, 3951.
4. (a) Johnson, W. S.; Elliott, R.; Elliott, J. D. JACS 1983, 105, 2904. (b) Tabor, A. B.; Holmes, A. B.; Baker, R. CC 1989, 1025. (c) Holmes, A. B.; Tabor, A. B.; Baker, R. JCS(P1) 1991, 3301, 3307.
5. (a) Elliott, J. D.; Choi, V. M. F.; Johnson, W. S. JOC 1983, 48, 2295. (b) Choi, V. M. F.; Elliott, J. D.; Johnson, W. S. TL 1984, 25, 591. (c) Solladié-Cavallo, A.; Suffert, J.; Gordon, M. TL 1988, 29, 2955.
6. (a) Johnson, W. S.; Edington, C.; Elliott, J. D.; Silverman, I. R. JACS 1984, 106, 7588. (b) Elliott, J. D.; Steele, J.; Johnson, W. S. TL 1985, 26, 2535.
7. (a) Alexakis, A.; Mangeney, P.; Ghribi, A.; Marek, I.; Sedrani, R.; Guir, C.; Normant, J. F. PAC 1988, 60, 49. (b) Normant, J. F.; Alexakis, A.; Ghribi, A.; Mangeney, P. T 1989, 45, 507.
8. Lindell, S. D.; Elliott, J. D.; Johnson, W. S. TL 1984, 25, 3947.
9. Mori, A.; Marvoka, K.; Yamamoto, H. TL 1984, 25, 4421.
10. Yamamoto, Y.; Abe, H.; Nishii, S.; Yamada, J. JCS(P1) 1991, 3253.
11. (a) Basile, T.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. CC 1989, 596. (b) Basile, T.; Tagiavini, E.; Trombini, C.; Umani-Ronchi, A. S 1990, 305.
12. Johnson, W. S.; Elliott, J. D.; Hanson, G. J. JACS 1984, 106, 1138.
13. (a) Ishihara, K.; Mori, A.; Arai, I.; Yamamoto, H. TL 1986, 27, 983. (b) Ishihara, K.; Mori, A.; Yamamoto, H. TL 1986, 27, 987. (c) Ishihara, K.; Mori, A.; Arai, I.; Yamamoto, H. T 1987, 43, 755.
14. Silverman, I. R.; Edington, C.; Elliott, J. D.; Johnson, W. S. JOC 1987, 52, 180.
15. Denmark, S. E.; Almstead, N. G. JACS 1991, 113, 8089.
16. (a) Naruse, Y.; Yamamoto, H. TL 1986, 27, 1363. (b) Mori, A.; Yamamoto, H. JOC 1985, 50, 5446. (c) Naruse, Y.; Yamamoto, H. T 1988, 44, 6021. (d) Kaino, M.; Naruse, Y.; Ishihara, K.; Yamamoto, H. JOC 1990, 55, 5814. (e) Underiner, T. L.; Paquette, L. A. JOC 1992, 57, 5438.
17. (a) Arai, I.; Mori, A.; Yamamoto, H. JACS 1985, 107, 8254. (b) Mori, A.; Arai, I.; Yamamoto, H. T 1986, 42, 6447.
18. Yoshikawa, M.; Sugimura, T.; Tai, A. CL 1990, 1003.
19. Kaino, M.; Ishihara, K.; Yamamoto, H. BCJ 1989, 62, 3736.
20. Chikashita, H.; Yuasa, T.; Itoh, K. CL 1992, 1457.
21. (a) Fukutani, Y.; Maruoka, K.; Yamamoto, H. TL 1984, 25, 5911. (b) Furuta, K.; Kanematsu, A.; Yamamoto, H.; Takaoka, S. TL 1989, 30, 7231. (c) Nonoshita, K.; Banno, H.; Maruoka, K.; Yamamoto, H. JACS 1990, 112, 316.
22. Lemière, G. L.; Dommisse, R. A.; Lepoivre, J. A.; Alderweireldt, F. C.; Hiemstra, H.; Wynberg, H.; Jones, J. B.; Toone, E. J. JACS 1987, 109, 1363.

J. Michael Chong

University of Waterloo, Ontario, Canada

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