[65253-04-5]  · C16H24O  · (-)-8-Phenylmenthol  · (MW 232.37) (1S,2R,5R)

[100101-42-6] (1S,2R,5S)


(chiral auxiliary for asymmetric induction)

Alternate Name: (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexanol.

Physical Data: [a]D -26° (c 2, EtOH); d 0.999 g cm-3.

Solubility: sol organic solvents.

Form Supplied in: commercially available as a colorless oil (98%) and as the chloroacetate ester.

Analysis of Reagent Purity: NMR and [a]D.

Preparative Methods: (1R,2S,5R)-(-)-8-phenylmenthol is prepared by the reaction of Phenylmagnesium Bromide (cat. Copper(I) Iodide) with (+)-pulegone, equilibration of the resulting conjugate addition product, and reduction of the ketone (Sodium, isopropanol).1 The (1R,2S,5R)-isomer is accompanied by the (1S,2R,5R)-isomer and is conveniently separated by recrystallization of the chloroacetate ester.2 This separation is essential to obtaining high optical yields since it has been shown that the two diastereomers have opposite chiral directing ability.3 The preparation of the enantiomeric (1S,2R,5S)-(+)-8-phenylmenthol from (+)-pulegone has been reported.4

Handling, Storage, and Precautions: no special precautions are necessary other than those used for combustible organic compounds.

Chiral Auxiliary for Asymmetric Induction.

Numerous derivatives of (-)-8-phenylmenthol have been utilized for asymmetric induction studies. These include inter-5 and intramolecular6 Diels-Alder reactions, dihydroxylations,7 and intramolecular ene reactions8 of a,b-unsaturated 8-phenylmenthol esters. These reactions usually proceed in moderate to good yield with high diastereofacial selectivity. a-Keto esters of 8-phenylmenthol (see 8-Phenylmenthyl Pyruvate) have been used for asymmetric addition to the keto group,9 as well as for asymmetric [2 + 2] photoadditions10 and nucleophilic alkylation.11 Ene reactions of a-imino esters of 8-phenylmenthol with alkenes provide a direct route to a-amino acids of high optical purity.12

Vinyl and butadienyl ethers of 8-phenylmenthol have been prepared and the diastereofacial selectivity of nitrone13 and Diels-Alder14 cycloadditions, respectively, have been evaluated. a-Anions of 8-phenylmenthol esters also show significant diastereofacial selectivity in aldol condensations15 and enantioselective alkene formation by reaction of achiral ketones with 8-phenylmenthyl phosphonoacetate gives de up to 90%.16

Related Reagents.

8-Phenylmenthyl Crotonate; 8-Phenylmenthyl Pyruvate.

1. Corey, E. J.; Ensley, H. E. JACS 1975, 97, 6908.
2. (a) Herzog, H.; Scharf, H. D. S 1986, 420. (b) Ort, O. OS 1987, 65, 203. (c) See also Cervinka, O.; Svatos, A.; Masojidkova, M. CCC 1990, 55, 491.
3. Whitesell, J. K.; Liu, C. L.; Buchanan, C. M.; Chen, H. H.; Minton, M. A. JOC 1986, 51, 551. Whitesell, J. K. CRV 1992, 92, 953.
4. Ensley, H. E.; Parnell, C. A.; Corey, E. J. JOC 1978, 43, 1610.
5. Oppolzer, W.; Kurth, M.; Reichlin, D.; Chapuis, C.; Mohnhaupt, M.; Moffat, F. HCA 1981, 64, 2802.
6. Roush, W. R.; Gillis, H. R.; Ko, A. I. JACS 1982, 104, 2269.
7. Hatakeyama, S.; Matsui, Y.; Suzuki, M.; Sakurai, K.; Takano, S. TL 1985, 26, 6485.
8. (a) Oppolzer, W.; Robbiani, C.; Bättig, K. HCA 1980, 63, 2015. (b) Oppolzer, W.; Robbiani, C.; Bättig, K. T 1984, 40, 1391.
9. (a) Grossen, P.; Herold, P.; Mohr, P.; Tamm, C. HCA 1984, 67, 1625. (b) Sugimura, H.; Yoshida, K. JOC 1993, 58, 4484. (c) Solladie-Cavallo, A.; Bencheqroun, M. TA 1991, 2, 1165. (d) Comins, D. L.; Baevsky, M. F.; Hong, H. JACS 1992, 114, 10 971.
10. (a) Koch, H.; Scharf, H. D.; Runsink, J.; Leismann, H. CB 1985, 118, 1485. (b) Nehrings, A.; Scharf, H.-D.; Runsink, J. AG(E) 1985, 24, 877.
11. Hamon, D. P. G.; Massy-Westropp, R. A.; Razzino, P. T 1992, 48, 5163.
12. Mikami, K.; Kaneko, M.; Yajima, T. TL 1993, 34, 4841.
13. Carruthers, W.; Coggins, P.; Weston, J. B. CC 1991, 117.
14. (a) Thiem, R.; Rotscheidt, K.; Breitmaier, E. S 1989, 836. (b) Danishefsky, S.; Bednarski, M.; Izawa, T.; Maring, C. JOC 1984, 49, 2290.
15. Corey, E. J.; Peterson, R. T. TL 1985, 26, 5025.
16. (a) Gais, H. J.; Schmiedl, G.; Ball, W. A. TL 1988, 29, 1773. (b) Rehwinkel, H.; Skupsch, J.; Vorbrüggen, H. TL 1988, 29, 1775.

Harry E. Ensley, Matthew Beggs & Yinghong Gao

Tulane University, New Orleans, LA, USA

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