8-Phenylmenthyl Acrylate

[72526-00-2]  · C19H26O2  · 8-Phenylmenthyl Acrylate  · (MW 286.45)

(reagent used in asymmetric synthesis for cycloadditions and conjugate additions)

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

Solubility: sol CH2Cl2, toluene, most organic solvents.

Analysis of Reagent Purity: 1H and 13C NMR.1 [a]D +16.21° (c 1.68, CH2Cl2).2

Preparative Method: prepared by the reaction of (-)-8-Phenylmenthol, acryloyl chloride, Triethylamine, and 4-Dimethylaminopyridine in CH2Cl2 at 0 °C. Following an aqueous workup, the compound is purified by chromatography on silica gel.1

Handling, Storage, and Precautions: acrylates are prone to polymerization and are best stored below room temperature under N2.

[4 + 2] Cycloadditions.

The asymmetric Diels-Alder reaction3 of phenylmenthyl acrylate with 5-benzyloxymethylcyclopentadiene in the presence of Aluminum Chloride produces an 89% yield of the endo cycloadduct (eq 1), accompanied by 7% of the exo adduct. This provides a useful intermediate for the preparation of various prostaglandins.2 The Tin(IV) Chloride and Titanium(IV) Chloride catalyzed reactions with Cyclopentadiene deliver a mixture of endo and exo adducts in 89% de, and 90% de, respectively (eq 2). The TiCl4 reaction gives an 89:11 endo:exo ratio, while the SnCl4 reaction gives an 84:16 endo:exo ratio. From a practical point of view, the titanium and tin catalysts are the best of the various Lewis acids surveyed.4 The use of TiCl4 is also the most effective for the reaction of the acrylate with 1,3-Butadiene (eq 3).5 The increased asymmetric induction over the simpler menthyl acrylate is attributed to the shielding of the C(a)-re face of the dienophile by the phenyl ring.6

1,3-Dipolar Cycloadditions.

The asymmetric induction for a 1,3-dipolar cycloaddition of phenylmenthyl acrylate is not as good as in the [4 + 2] cycloadditions. The thermal decomposition of diazofluorene in the presence of the acrylate produces the spirocyclopropane in 96% yield, but with only a 20% de (eq 4).7

Conjugate Additions.

The reaction of this acrylate derivative with lithium t-butyl hydroperoxide (generated from anhydrous t-Butyl Hydroperoxide and n-Butyllithium) in THF leads to the corresponding epoxide (eq 5) in 95% yield with a de of 40%.8

In an asymmetric approach to the bicyclo[2.2.2]octane ring system, a double Michael addition has been employed using phenylmenthyl acrylate as the initial Michael acceptor. The condensation of the dienolate, generated with Lithium Diisopropylamide, reacts with the acrylate to afford the bicyclo[2.2.2]octane derivative (eq 6). The de for the reaction is only 50%; however, it is highly endo selective (>95%).9

A Lewis acid-mediated two-fold asymmetric Michael addition allows access to cis-decalin derivatives. The reaction of the trimethylsilylenol ether of acetylcyclohexene with phenylmenthyl acrylate in the presence of Diethylaluminum Chloride (eq 7) yields the decalone in 64% yield (70% de). This has been shown not to be a Diels-Alder reaction. If the reaction is worked-up early, the initial Michael adduct can be isolated.10

Phenylmenthyl acrylate has been used as a component in an asymmetric Baylis-Hillman reaction. Treatment of the acrylate with 1,4-Diazabicyclo[2.2.2]octane and benzaldehyde at 8 kbar of pressure delivers the a-(hydroxyalkyl)acrylate (eq 8). The product obtained has an 86% de. Menthyl acrylate is superior to the phenylmenthyl acrylate in this particular application.11 In a radical-mediated addition, phenylmenthyl acrylate gives rise to the a-pyridyl sulfide in 68% yield (eq 9).12 The final product is isolated with a 56% de.


The acrylate provides a synthon for the preparation of 8-Phenylmenthyl Glyoxylate, which is useful for asymmetric ene reactions.1 Thus ozonolysis and removal of the water of hydration produces the glyoxylate in 89% yield (eq 10).

1. Whitesell, J. K.; Bhattacharya, A.; Buchnan, C. M.; Chen, H. H.; Deyo, D.; James, D.; Liu, C.-L.; Minton, M. A. T 1986, 42, 2993.
2. Corey, E. J.; Ensley, H. E. JACS 1975, 97, 6908.
3. (a) Oppolzer, W. AGE 1984, 23, 876. (b) Paquette, L. A. Asymmetric Synthesis; Morrison, J. D., Ed.; Academic: Orlando, 1984; Vol. 3B, pp 455-501. (c) Helmchen, G.; Karge, R.; Weetman, J. Modern Synthetic Methods; Scheffold, R. Ed.; Springer: Berlin, 1986; Vol. 4, pp 262-306. (d) Taschner, M. J. Organic Synthesis: Theory and Applications; Hudlicky, T., Ed.; JAI: Greenwich, CT, 1989; Vol. 1, pp 1-101.
4. Oppolzer, W.; Kurth, M.; Reichlin, D.; Moffatt, F. TL 1981, 22, 2545.
5. (a) Boeckman, R. K.; Naegely, P. C.; Arthur, S. D. JOC 1980, 45, 752. (b) Kocienski, P.; Stocks, M.; Donald, D.; Perry, M. SL 1990, 38.
6. Oppolzer, W.; Kurth, M.; Reichlin, D.; Chapius, C.; Mohnhaupt, M.; Moffatt, F. HCA 1981, 64, 2802.
7. Okada, K.; Samizo, F.; Oda, M. CL 1987, 93.
8. (a) Clark, C.; Hermans, P.; Meth-Cohn, O.; Moore, C.; Taljaard, H. C.; van Vuuren, G. CC 1986, 1378. (b) Meth-Cohn, O.; Moore, C.; Taljaard, H. C. JCS(P1) 1988, 2663.
9. Spitzner, D.; Wagner, P.; Simon, A.; Peters, K. TL 1989, 30, 547.
10. Hagiwara, H.; Akama, T.; Okano, A.; Uda, H. CL 1989, 2149.
11. Gilbert, A.; Heritage, T. W.; Isaacs, N. S. TA 1991, 2, 969.
12. Crich, D.; Davies, J. W. TL 1987, 28, 4205.

Michael J. Taschner

The University of Akron, OH, USA

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