8-Phenylmenthyl Glyoxylate1

[129444-92-4]  · C18H24O3  · 8-Phenylmenthyl Glyoxylate  · (MW 288.42)

(two-carbon unit utilized as a versatile chiral reagent in ene reactions,2 Diels-Alder reactions,3 various nucleophilic additions,4 and aromatic substitutions.5)

Physical Data: bp 135-140 °C/0.3 mmHg; [a]20589 -169° (c 0.51, benzene).6

Solubility: sol most common organic solvents.

Preparative Methods: ozonolysis of 8-Phenylmenthyl Acrylate, NaOAc-catalyzed elimination of nitrite ion from nitrate esters, and direct esterification with glyoxylic acid.7

Handling, Storage, and Precautions: heating the glyoxylate monohydrate to 90 °C/0.1 mmHg for 4.5 h or distillation provides material which is sufficiently anhydrous for most practical applications. Due to its tendency to form a monohydrate and/or polymerize, 8-phenylmenthyl glyoxylate should be stored under nitrogen in the refrigerator.

Ene Reactions.

Lewis acid (Tin(IV) Chloride or Titanium(IV) Chloride) catalyzed ene reactions of the glyoxylate esters of 8-phenylmenthol and 2-epi,ent-8-phenylmenthol, as well as trans-2-phenylcyclohexanol, with terminal, monosubstituted alkenes proceed with excellent levels of stereocontrol (eq 1).8 The phenyl group presumably forms a p-complex with the aldehyde-Lewis acid complex thereby blocking one face of the dicarbonyl, rendering the opposite face accessible to incoming reagents. This has been demonstrated through the systematic study of the effect of auxiliary structure on asymmetric induction in the glyoxylate-ene reaction, as well as by photophysical studies involving a family of a-carbonyl esters of 8-phenylmenthol.7,9 The ene reactions of glyoxylates with nonterminal alkenes proceed with a high level of relative asymmetric induction to give the (S)-configuration at the newly created stereocenter with 8-phenylmenthol and the (R)-configuration with trans-2-phenylcyclohexanol. The reaction of 8-phenylmenthyl glyoxylate with trans-2-butene produces a 93:7 mixture of diastereomers at C-3 in 85% yield; introduction of a TMS group into trans-2-butene increases the anti-selectivity up to ~100% (eq 2).8f,g Double bond isomerization in the substrate under the reaction conditions, as well as contamination of halogen adducts in the products, point to a cationic mechanism for these ene reactions.8e

The asymmetric glyoxylate-ene reactions have been exploited in the total synthesis of (-)-specionin, which involves asymmetric desymmetrization of a prochiral diene (eq 3), and (-)-xylomollin, which involves an efficient kinetic resolution of a racemic diene (eq 4).10a-c

Nucleophilic Additions.

A variety of nucleophiles have been added to 8-phenylmenthyl (and trans-2-phenylcyclohexyl) glyoxylates with high levels of asymmetric induction. These include organomagnesium4 and organotin reagents,11 as well as nitroalkane anions (eq 5).12 Other applications of 8-phenylmenthyl glyoxylate include asymmetric hetero-Diels-Alder reactions to produce chiral dihydropyran derivatives3 and o-hydroxylation of phenols producing the corresponding chiral 2-hydroxymandelic acid derivatives.5 a-Imino esters derived from 8-phenylmenthyl glyoxylate undergo nucleophilic additions13 as well as ene reactions14 to produce nonproteinogenic a-amino acid derivatives.

1. Whitesell, J. K. CRV 1992, 92, 953.
2. Mikami, K.; Shimizu, M. CRV 1992, 92, 1021.
3. Cervinka, O.; Svatos, A.; Trska, P.; Pech, P. CCC 1990, 55, 230.
4. (a) Whitesell, J. K.; Bhattacharya, A.; Henke, K. CC 1982, 988. (b) Whitesell, J. K.; Deyo, D.; Bhattacharya, A. CC 1983, 802. (c) Whitesell, J. K.; Buchanan, C. M. JOC 1986, 51, 5443.
5. Bigi, F.; Casnati, G.; Sartori, G.; Dalprato, C.; Bortolini, R. TA 1990, 2, 861.
6. Cervinka, O.; Svatos, A.; Masojidkova, M. CCC 1990, 55, 491.
7. Whitesell, J. K.; Lawrence, R. M.; Huang-Hsing, C. JOC 1986, 51, 4779.
8. (a) Whitesell, J. K.; Bhattacharya, A.; Aguilar, D. A. A.; Henke, K. CC 1982, 989. (b) Whitesell, J. K.; Bhattacharya, A.; Buchanan, C. M.; Chen, H. H.; Deyo, D. T 1986, 42, 2993. (c) Whitesell, J. K.; Chen, H. H.; Lawrence, R. M. JOC 1985, 50, 4663. (d) Whitesell, J. K.; Liu, C.; Buchanan, C.; Chen, H-H.; Minton, M. M. JOC 1986, 51, 551. (e) Whitesell, J. K. ACR 1985, 18, 280. (f) Mikami, K.; Wakabayashi, H.; Nakai, T. JOC 1991, 56, 4337. (g) Grossen, P.; Herold, P.; Mohr, P.; Tamm, C. HCA 1984, 67, 1625.
9. Whitesell, J. K.; Younathan, J. N.; Hurst, J. R.; Fox, M. A. JOC 1985, 50, 5499.
10. (a) Whitesell, J. K.; Allen, D. E. JOC 1985, 50, 3025. (b) Whitesell, J. K.; Allen, D. E. JACS 1988, 110, 3558. (c) Whitesell, J. K.; Minton, M. A. JACS 1986, 108, 6802.
11. (a) Yamamoto, Y.; Maeda, N.; Maryuma, K. CC 1983, 774. (b) Yamamoto, Y.; Yatagai, H.; Ishihara, Y.; Maeda, N.; Maryuma, K. T 1984, 40, 2239.
12. (a) Solladie-Cavallo, A.; Khiar, N. TL 1988, 2189. (b) Solladie-Cavallo, A.; Khiar, N.; Fischer, J.; DeCian, A. T 1991, 47, 249. (c) Solladie-Cavallo, A.; Khiar, N. JOC 1990, 55, 4750.
13. Yamamoto, Y.; Ito, W. T 1988, 44, 5415.
14. Mikami, K.; Kaneko, M.; Yajima, T. TL 1993, 34, 4841.

Apurba Bhattacharya

Hoechst-Celanese Corporation, Corpus Christi, TX, USA

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