Phenylmenthyl acrylate

Carruthers, W. Coggins, P. Weston, J. B. Chem. Commun./J. Chem. Soc., Chem. Commun. 1991, 117. 

Harry E. Ensley, Matthew Beggs Yinghong Gao Tulane University, New Orleans, LA, USA 

Alternate Name (17 ,2S,57 )-2-( 1-methyl-l-phenylethyl)-5-me-thylcyclohexyl acrylate. 

Solubility sol CH2CI2, toluene, most organic solvents. 

Preparative Methods prepared by the reaction of (-)-8-Phenylmenthol, acryloyl chloride, Triethylamine, and 4-Dimethylaminopyridine in CH2CI2 at 0 °C. Following an aqueous workup, the compound is purified by chromatography on silica gel.  

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Asymmetric Diels-Alder reactions. The acrylate of (+ )-l is markedly superior to ( —)-menthyl acrylate in effecting asymmetric induction in Diels-Alder reaction with cyclopentadiene (Lewis acid catalysis, equation I). A chiral intermediate in Corey s prostaglandin synthesis was obtained by the reaction of (-1- )-8-phenylmenthyl acrylate with a cyclopentadiene derivative.1... 

Asymmetric ene reactions.5 A key step in an asymmetric synthesis of the amino diacid (+ )-a-allokainic acid (5) involves an intramolecular ene reaction of the (Z)-diene 2, in which the enophile is a (Z)-( —)-8-phenylmenthyl acrylate unit. In the presence of (C2H5)2A1C1, (Z)-2 cyclizes to the two pyrrolidines 3 and 4 in the ratio of... 

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

Most importantly, even asymmetric induction with a maximum of 64 % d.e. is achievable by starting with optically active 8-phenylmenthyl acrylate" . Recently the Binger group has also reported the cycloadditions to alkynylsilanes forming 4-methylene-1-cyclopentenes (equations 194 and 195)" However, in many examples regiochemical problems concerning methylenecyclopropane as well as alkyne substituents might limit practical application. 

The first synthetically useful application reported used ( + )-8-phenylmenthyl acrylate (+)-(lf) as chiral dienophile for the asymmetric synthesis of the prostaglandin intermediate 129. 

Silica-supported Lewis acids (e. g. ZnCl2, Znl2, or TiCl4) were also studied in Diels-Alder reactions of furan [37,38]. Reactions were performed at 25 °C and the best results were obtained in the absence of solvent. The combination of dienophile and supported Lewis acid had a great influence on the outcome of the reactions. Reaction with the chiral dienophile (-)-8-phenylmenthyl acrylate gave the endo adduct in 68 % d. e. and the exo adduct in 70 % d. e. [37]. 

The trimethylsilyl enol ethers of 1-acetylcyclohexenes 1 undergo a Lewis acid assisted two fold Michael reactions with Michael acceptors 2 to produce 5-substituted 2-decalones 3. The application of these reactions have enabled syntheses of ( )-8-cadinene 4, ( )-khusitone 5, and ( )-khusilal 6. By employing 8- phenylmenthyl acrylate, optically active 2-decalone 3 (ca. 

TributylstannylmethyI)acrylonitrile (4.0 equiv.) is added to a solution of 8-phenylmenthyl acrylate (0.4 mmol) and AIBN (5 mol%) in benzene (2.5 mL). The mixture is stirred at 69 °C for 4 h. After completion of the reaction is confirmed, the reaction mixture is concentrated and the residue is purified by silica gel column chromatography to give the title adduct in 69% yield (d.r. 86 14). ... 

Cycloadditions. The asymmetric Diels-Alder reaction of phenylmenthyl acrylate with 5-benzyloxymethyl-cyclopentadiene 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. The Tin(IV) Chloride and Titanium(IV) Chloride catalyzed reactions with Cyclopenta-diene deliver a mixture of endo and exo adducts in 89% de, and 90% de, respectively (eq 2). The TiCU reaction gives an 89 11 endo. exo ratio, while the SnCU reaction gives an 84 16 endoiexo ratio. From a practical point of view, the titanium and tin catalysts are the best of the various Lewis acids surveyed. The use of TiCl4 is also the most effective for the reaction of the acrylate... 

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 di-azofluorene in the presence of the acrylate produces the spirocy-clopropane in 96% yield, but with only a 20% de (eq 4). ... 

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%). ... 

A Lewis acid-mediated two-fold asymmetric Michael addition allows access to c( s-decalin derivatives. The reaction of the trimethylsilylenol ether of acety Icyclohexene 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. ... 

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. In a radical-mediated addition, phenylmenthyl acrylate gives rise to the a-pyridyl sulfide in 68% yield (eq 9). The final product is isolated with a 56% de. 

The formation of spirocyclopropanes from the reaction of diazodiphenylmethane and ( )-8-phenylmenthyl esters of acrylic acid and methyl fumarate occurred with a modest level of diastereofacial selectivity (136). In contrast, diastereoselectivities of 90 10 were achieved in the cycloadditions of diazo(trimethylsilyl)methane with acrylamides 65 derived from camphor sultam as the chiral auxiliary (137) (Scheme 8.16). Interestingly, the initial cycloadducts 66 afforded the nonconjugated A -pyrazolines 67 on protodesilylation the latter were converted into optically active azaproline derivatives 68. In a related manner, acrylamide 69 was converted into A -pyrazolines 70a,b (138). The major diastereoisomer 70a was used to synthesize indolizidine 71. The key step in this synthesis involves the hydrogenolytic cleavage of the pyrazoline ring. 

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

Simpler, open-chain, chiral alkenes have also been employed in [3 + 2]-cycloaddition reactions in order to obtain face selectivity of the addition. The introduction of chiral alcohols such as ( —)-(l/ ,27 ,5S)-menthol into acrylic esters provides a simple entry into this field however, the conformational variability of such molecules allows for only relatively low stereoselectivities.The same is true for the (— )-(l /J,2i ,4i )-bornyl and (— )-(l 7 ,27 ,55)-8-phenylmenthyl derivatives. ... 

If the asymmetric fragment exerting diastereomeric control were removable, and were itself optically pure, the result would be an enantioselective cyclization. Chiral acrylates have been used in the intermolecular Diels-Alder reaction, one of the more effective to date being phenylmenthyl (54). Roush has shown [56] that phenylmenthyl esters exert substantial diastereomeric control in the intramolecular Diels-Alder reaction also. 

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