10-Camphorsulfonyl Chloride1

(1R)

[21286-54-4]  · C10H15ClO3S  · 10-Camphorsulfonyl Chloride  · (MW 250.75) (1S)

[39262-22-1] (±)

[6994-93-0]

(enantiomeric excess determination;2 chemical resolution;3 synthesis of chiral auxiliaries;4 chiral precursor for natural product synthesis;1 synthesis of chiral reagents5)

Physical Data: mp 65-67 °C; (1S)-(+): [a]D + 32.1° (c 1, CHCl3).

Solubility: sol CH2Cl2; slightly sol ether; insol H2O.

Form Supplied in: both enantiomers and the racemic sulfonyl chloride are commercially available.

Preparative Methods: can be prepared from 10-Camphorsulfonic Acid upon treatment with Phosphorus(V) Chloride or Thionyl Chloride.6

Purification: crystallized from hexane or from MeOH.

Handling, Storage, and Precautions: corrosive and moisture-sensitive. This reagent should be handled in a fume hood.

Reagent for Determination of Enantiomeric Excesses and for Chemical Resolution of Alcohols and Amines.

10-Camphorsulfonyl chloride has been widely used as a chiral derivatizing agent for the assay of enantiomeric purity of alcohols and amines by NMR techniques.2 A typical procedure for the preparation of the sulfonate ester or sulfonamide involves mixing a solution of the alcohol or amine in CH2Cl2 with camphorsulfonyl chloride in the presence of an amine base (Et3N, py, or DMAP). This reagent has been particularly valuable for determining the enantiomeric purity of secondary alcohols (1, 2) and b-hydroxy esters (3).7

In some cases (3), the addition of a chiral shift reagent (Eu(hfc)3) is necessary to obtain baseline separation of the signals corresponding to the b-proton of both diastereomers by 1H NMR. Diastereomeric mixtures derived from secondary alcohols have also been analyzed by HPLC.8 The resolution of a secondary alcohol (4) could be achieved by a selective crystallization of one of the two diastereomeric camphorsulfonate esters.3

The enantiomeric purities of primary and secondary amines have also been established by 1H NMR spectroscopy by their conversion into the corresponding sulfonamide. These derivatives often produce crystalline compounds that are suitable for X-ray crystallographic studies. For example, the enantiomeric purities of amines (5),9 (6),10 and (7)11 were determined by 1H NMR spectroscopy and the absolute stereochemistry of (7) was unequivocally established by X-ray crystallography.

A general protocol for the HPLC separation of diastereomeric camphorsulfonamides12 derived from racemic a-amino acids has been developed (eq 1).13 More complex amino acids, such as (8), were successfully analyzed by this procedure.14

Synthesis of Chiral Auxiliaries.

Their availability and crystalline nature has made camphor derivatives the precursors of choice for the design and synthesis of chiral auxiliaries.4 10-Camphorsulfonyl chloride is the starting material for the synthesis of chiral auxiliaries (9)-(12) (eq 2). Sulfonamides (9) and (10)15 have been used as chiral auxiliaries in a number of reactions, e.g. the Lewis acid-catalyzed Diels-Alder reaction, the [3 + 2] cycloaddition of a nitrile oxide to an acrylate, and the stereoselective conjugate addition reaction of organocopper reagents to a,b-unsaturated esters.4

In addition to being an efficient chiral controller in a number of stereoselective transformations of chiral acrylates, (i.e. the Diels-Alder reaction,4 the conjugate reduction,16 the asymmetric dihydroxylation,17 and the nitrile oxide cycloaddition18) the bornanesultam (11)19 has been shown to be an exceptionally efficient chiral auxiliary for stereoselective aldol condensations (eqs 3 and 4). Depending upon the reaction conditions, N-propionylsultam can produce either the syn or anti aldol product with an excellent diastereoselectivity.20 Furthermore, good diastereoselectivities are also observed for the corresponding acetate aldol reaction (eq 5).21

Oxathiane (12) has been shown to be an efficient chiral auxiliary in the nucleophilic addition to carbonyl compounds.22

10-Camphorsulfonyl chloride has also been widely used as a useful precursor to chiral dienophiles in hetero-Diels-Alder reactions.23

An elegant use of the chirality and the leaving group ability of the camphorsulfonate ester has been reported in the synthesis of a chiral C2 symmetric cyclopentadienyl ligand (eq 6).24

Synthesis of Chiral Reagents.

An efficient chiral a-chloro-a-nitroso reagent derived from 10-camphorsulfonyl chloride (1. Cy2NH; 2. NH2OH; 3. t-BuOCl; 70-78%) has been developed for the asymmetric a-amination of ketone enolates (eq 7).25 The resulting b-keto N-hydroxylamine can be converted to the anti-1,2-hydroxyamine under reducing conditions (NaBH4; Zn, HCl, AcOH).

Several oxaziridines related to (14)5 (eq 8) have been used, most notably in the enantioselective oxidation of sulfides to sulfoxides,26 of selenides to selenoxides,27 and of alkenes to oxiranes.28 It is also the reagent of choice for the hydroxylation of lithium and Grignard reagents29 and for the asymmetric oxidation of enolates to give a-hydroxy carbonyl compounds.5,30 A similar chiral fluorinating reagent has also been developed.31

Chiral Precursor for Natural Product Synthesis.

10-Camphorsulfonyl chloride has been used as a chiral starting material for the synthesis of a number of products1 such as ketopinic acid32 (eq 9), which has been used to resolve alcohols33 and hemiacetals.34


1. Money, T. Nat. Prod. Rep. 1985, 2, 253.
2. (a) Parker, D. CRV 1991, 91, 1441. (b) Weisman, G. R. Asymm. Synth. 1983, 1, 153.
3. Tsuchihashi, G.-I.; Mitamura, S.; Kitajima, K.; Kobayashi, K. TL 1982, 23, 5427.
4. Oppolzer, W. T 1987, 43, 1969.
5. Davis, F. A.; Chen, B.-C. CRV 1992, 92, 919.
6. Bartlett, P. D.; Knox, L. H. OSC 1973, 5, 196
7. (a) Quinkert, G.; Küber, F.; Knauf, W.; Wacker, M.; Koch, U.; Becker, H.; Nestler, H. P.; Dürner, G.; Zimmermann, G.; Bats, J. W.; Egert, E. HCA 1991, 74, 1853. (b) Quinkert, G.; Döller, U.; Eichhorn, M.; Küber, F.; Nestler, H. P.; Becker, H.; Bats, J. W.; Zimmermann, G.; Dürner, G. HCA 1990, 73, 1999. (c) Quinkert, G.; Fernholz, E.; Eckes, P.; Neumann, D.; Dürner, G. HCA 1989, 72, 1753.
8. Mori, K.; Kisida, H. LA 1989, 35.
9. Dehmlow, E. V.; Westerheide, R. S 1992, 947.
10. Theodore, L. J.; Nelson, W. L. JOC 1987, 52, 1309.
11. Braun, H.; Felber, H.; Kresze, G.; Schmidtchen, F. P.; Prewo, R.; Vasella, A. LA 1993, 261.
12. Burke, T. R., Jr.; Nelson, W. L.; Mangion, M.; Hite, G. J.; Mokler, C. M.; Ruenitz, P. C. JMC 1980, 23, 1044.
13. (a) Furukawa, H.; Mori, Y.; Takeuchi, Y.; Ito, K. J. Chromatogr. 1977, 136, 428. (b) Furukawa, H.; Sakakibara, E.; Kamei, A.; Ito, K. CPB 1975, 23, 1625.
14. Berthet, M.; Sonveaux, E. CC 1983, 10.
15. Oppolzer, W.; Chapuis, C.; Bernardinelli, G. TL 1984, 25, 5885.
16. Oppolzer, W.; Poli, G.; Starkemann, C.; Bernardinelli, G. TL 1988, 29, 3559.
17. Oppolzer, W.; Barras, J.-P. HCA 1987, 70, 1666.
18. Curran, D. P.; Kim, B. H.; Daugherty, J.; Heffner, T. A. TL 1988, 29, 3555.
19. (a) Davis, F. A.; Towson, J. C.; Weismiller, M. C.; Lal, S.; Carroll, P. J. JACS 1988, 110, 8477. (b) Weismiller, M. C.; Towson, J. C.; Davis, F. A. OS 1990, 69, 154. (c) Towson, J. C.; Weismiller, M. C.; Lal, G. S.; Sheppard, A. C.; Davis, F. A. OS 1990, 69, 158.
20. Syn aldol: (a) Oppolzer, W.; Blagg, J.; Rodriguez, I.; Walther, E. JACS 1990, 112, 2767. Anti aldol: (b) Oppolzer, W.; Lienard, P. TL 1993, 34, 4321. (c) Oppolzer, W.; Starkemann, C.; Rodriguez, I.; Bernardinelli, G. TL 1991, 32, 61.
21. Oppolzer, W.; Starkemann, C. TL 1992, 33, 2439.
22. Eliel, E. L.; Frazee, W. J. JOC 1979, 44, 3598.
23. (a) Braun, H.; Felber, H.; Kresze, G.; Schmidtchen, F. P.; Prewo, R.; Vasella, A. LA 1993, 261. (b) Blanco, J. M.; Caamaño, O.; Eirin, A.; Fernandez, F.; Medina, L. BSB 1989, 98, 923. (c) Caamaño, O.; Eirín, A.; Fernandez, F.; Gómez, G.; Uriarte, E. H 1988, 27, 2839. (d) De Lucchi, O.; Lucchini, V.; Marchioro, C.; Valle, G.; Modena, G. JOC 1986, 51, 1457.
24. Halterman, R. L.; Vollhardt, K. P. C.; Welker, M. E.; Bläser, D.; Boese, R. JACS 1987, 109, 8105.
25. Oppolzer, W.; Tamura, O.; Sundarababu, G.; Signer, M. JACS 1992, 114, 5900.
26. Davis, F. A.; McCauley, Jr., J. P.; Chattopadhyay, S.; Harakal, M. E.; Towson, J. C.; Watson, W. H.; Tavanaiepour, I. JACS 1987, 109, 3370.
27. Davis, F. A.; Reddy, R. T. JOC 1992, 57, 2599.
28. Davis, F. A.; Chattopadhyay, S. TL 1986, 27, 5079.
29. (a) Davis, F. A.; Wei, J.; Sheppard, A. C.; Gubernick, S. TL 1987, 28, 5115. (b) Davis, F. A.; Lal, G. S.; Wei, J. TL 1988, 29, 4269.
30. Davis, F. A.; Kumar, A. JOC 1992, 57, 3337.
31. Differding, E.; Lang, R. W. TL 1988, 29, 6087.
32. Haslanger, M. F.; Heikes, J. S 1981, 801.
33. Paulsen, H.; Brauer, O. CB 1977, 110, 331.
34. Woodward, R. B.; Gosteli, J.; Ernest, I.; Friary, R. J.; Nestler, G.; Raman, H.; Sitrin, R.; Suter, C.; Whitesell, J. K. JACS 1973, 95, 6853.

André B. Charette

Université de Montréal, Québec, Canada



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