(-)-(1S,4R)-Camphanic Acid1

(1S)

[13429-83-9]  · C10H14O4  · (-)-(1S,4R)-Camphanic Acid  · (MW 198.22) (1R)

[67111-66-4] (±)

[465-48-5]

(enantiomeric purity determination;2 chemical resolution;3 chiral auxiliaries4)

Physical Data: mp 201-204 °C; (1S): [a]D -20.4° (c 1.71, dioxane); [a]D -18° (c 1, dioxane).

Solubility: sol EtOH, ether, boiling H2O, and AcOH.

Form Supplied in: white solid.

Preparative Methods: commercially available. Alternatively, the acid can be prepared in two steps from camphoric acid (1. PCl5; 2. H2SO4; 65% overall yield). The acid can be converted to the corresponding acid chloride upon treatment with Thionyl Chloride (99% yield).1,5

Purification: crystallized from hot toluene.

Handling, Storage, and Precautions: stable; no special precautions.

Analysis of the Enantiomeric Purity of Alcohols and Amines.

It has been shown that camphanic acid is an efficient chiral derivatizing agent for the determination of the enantiomeric purity of alcohols and amines.2 A typical procedure involves mixing a solution of the amine or the alcohol (in CH2Cl2, py, or benzene) with camphanoyl chloride in the presence of a base (Et3N, py, DMAP, or NaHCO3). Alternatively, the substrate can be coupled directly with camphanic acid in the presence of DCC/DMAP. These conditions, however, can potentially lead to significant kinetic resolution.6 Camphanic acid was initially developed for the analysis of the enantiomeric purity of a-deuterated primary alcohols7 and amines.8 Distinct signals by 1H NMR for the two diastereomers can usually be observed upon addition of a chiral shift reagent or when using C6D6 as the solvent.9 Since then, this chiral derivatizing agent has been widely used for measuring the enantiomeric excess of several classes of compounds such as a-monodeuterated glycine derivatives (1),10 a-and b-amino acids (2, 3),11,12 a,a-disubstituted a-amino acids (4),13 secondary alcohols (5),14 1,2-amino alcohols (6),15 and sulfoximines.16

Resolution of Alcohols.

In addition to generally providing highly crystalline derivatives that are usually suitable for X-ray crystallographic studies,17 diastereomeric esters derived from camphanic acid have been widely used in organic synthesis for the resolution of racemic alcohols by fractional crystallization or chromatography.18 This is one of the methods of choice to resolve inositol derivatives.19 Selected examples are shown in (7)-(10).20

Chiral Auxiliary for Cycloaddition Reactions.

Camphanate ester (11) has been used as a chiral dienophile in cycloaddition reactions with substituted furans to produce 7-oxabicyclo[2.2.1]heptene derivatives (eq 1).4,21


1. Gerlach, H.; Kappes, D.; Boeckman, Jr., R. K.; Maw, G. N. OS 1993, 71, 48.
2. Parker, D. CRV 1991, 91, 1441.
3. Wilen, S. H. Top. Stereochem. 1971, 6, 107.
4. Vieira, E.; Vogel, P. HCA 1983, 66, 1865.
5. Kappes, D.; Gerlach, H. SC 1990, 20, 581.
6. Chinchilla, R.; Najera, C.; Yus, M.; Heumann, A. TA 1990, 1, 851.
7. Gerlach, H.; Zagalak, B. CC 1973, 274.
8. (a) Parker, D. JCS(P2) 1983, 83. (b) Parker, D.; Taylor, R. J.; Ferguson, G.; Tonge, A. T 1986, 42, 617.
9. (a) Schwab, J. M.; Ray, T.; Ho, C.-K. JACS 1989, 111, 1057. (b) Prabhakaran, P. C.; Gould, S. J.; Orr, G. R.; Coward, J. K. JACS 1988, 110, 5779. (c) Schwab, J. M.; Li, W.; Thomas, L. P. JACS 1983, 105, 4800.
10. (a) Armarego, W. L. F.; Milloy, B. A.; Pendergast, W. JCS(P1) 1976, 2229. (b) Hamon, D. P. G.; Massy-Westropp, R. A.; Razzino, P. T 1993, 49, 6419. (c) Hegedus, L. S.; Lastra, E.; Narukawa, Y.; Snustad, D. C. JACS 1992, 114, 2991. (d) Williams, R. M.; Zhai, D.; Sinclair, P. J. JOC 1986, 51, 5021.
11. (a) Jackson, R. F. W.; Wishart, N.; Wood, A.; James, K.; Wythes, M. J. JOC 1992, 57, 3397. (b) Lowe, C.; Pu, Y.; Vederas, J. C. JOC 1992, 57, 10. (c) Arnold, L. D.; Drover, J. C. G.; Vederas, J. C. JACS 1987, 109, 4649. (d) Trimble, L. A.; Vederas, J. C. JACS 1986, 108, 6397.
12. Jefford, C. W.; Wang, J. TL 1993, 34, 1111.
13. Yee, C.; Blythe, T. A.; McNabb, T. J.; Walts, A. E. JOC 1992, 57, 3525.
14. Hafner, A.; Duthaler, R. O.; Marti, R.; Rihs, G.; Rothe-Streit, P.; Schwarzenbach, F. JACS 1992, 114, 2321.
15. Williams, R. M.; Sinclair, P. J.; Zhai, D.; Chen, D. JACS 1988, 110, 1547.
16. Shiner, C. S.; Berks, A. H. JOC 1988, 53, 5542.
17. See, for examples: (a) Oppenländer, T.; Schönholzer, P. HCA 1989, 72, 1792. (b) Eberle, M.; Egli, M.; Seebach, D. HCA 1988, 71, 1. (c) Estermann, H.; Prasad, K.; Shapiro, M. J.; Repic, O.; Hardtmann, G. E.; Bolsterli, J. J.; Walkinshaw, M. D. TL 1990, 31, 445.
18. Gerlach, H. HCA 1968, 51, 1587.
19. Billington, D. C.; Baker, R.; Kulagowski, J. J.; Mawer, I. M. CC 1987, 314.
20. (a) (7): Mori, K.; Waku, M. T 1985, 41, 5653. (b) (8): Naemura, K.; Ueno, M. BCJ 1990, 63, 3695. (c) (9): Vacca, J. P.; DeSolms, S. J.; Huff, J. R. JACS 1987, 109, 3478. (d) (10): Tochtermann, W.; Scholz, G.; Bunte, G.; Wolff, C.; Peters, E.-M.; Peters, K.; Von Schnering, H. G. LA 1992, 1069.
21. (a) Wagner, J.; Vogel, P. TL 1991, 32, 3169. (b) Kernen, P.; Vogel, P. TL 1993, 34, 2473.

André B. Charette

Université de Montréal, Québec, Canada



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