Phenylmenthyl group reaction

This sequence was obviously not amenable to a synthesis of optically active a-allokainic acid given the fact that an aminomalonate group was necessary. After unfruitful assays with menthyl esters, the Swiss group was rewarded by the discovery that the phenylmenthyl group (180) brings sufficient asymmetry to the reaction intermediate to afford products with a high percentage of favorable diastereoisomer (Scheme 35) (181). 

A remarkable feature of this reaction is that it creates three chiral centers. Two of the chiral centers, namely those at the two ring junctions, are established by the Diels-Alder reaction. The third, namely the endo position of the ester group, is also established by the Diels-Alder reaction. Without the chiral auxiliary 8-phenylmenthyl group, two of the eight possible stereoisomers would be produced, namely the pair of enantiomers shown. Although both enantiomers of the bicyclic products were formed in Corey s scheme, they were formed in the ratio of 97 3 and the desired enantiomer could be separated in pure form. In subsequent steps, the 8-phenylmenthyl ester was hydrolyzed and the pure enantiomer was converted to the so-called Corey lactone and then to enantiometically pure prostaglandin... 

Chiral Auxiliary for Asymmetric Induction. Numerous derivatives of (—)-8-phenylmenthol have been utilized for asymmetric induction studies. These include inter- and intramolecular Diels-Alder reactions, dihydroxylations, and intramolecular ene reactions of a,p-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, as well as for asymmetric [2 -F 2] photoadditions and nucleophilic alkylation. Ene reactions of a-imino esters of 8-phenylmenthol with alkenes provide a direct route to a-amino acids of high optical purity. Vinyl and butadienyl ethers of 8-phenylmenthol have been prepared and the diastereofacial selectivity of nitrone and Diels-Alder cycloadditions, respectively, have been evaluated. a-Anions of 8-phenylmenthol esters also show significant diastereofacial selectivity in aldol condensations and enantiose-lective alkene formation by reaction of achiral ketones with 8-phenylmenthyl phosphonoacetate gives de up to 90%. ... 

Oppolzer and cowoikers have developed an enantioselective version of this reaction which permits the synthesis of (+)- and (-)-a-allokainic acid from (76) and (77), respectively. - Treatment of (-)-8-phe-nylmenthyl ester (74) with EtAlCh at -78 C gives a 95 5 mixture of (76) and (77). Treatment of (-)-8-phenylmenthyl ester (75) with EtAlCh at -35 C gives an 11 89 mixture of (76) and (77). Oppolzer and Mirza used C labeling to establish that the hydrogen is transferred exclusively from the frons-methyl group of (69). This result precludes a stepwise mechanism with a free cationic intermediate which should transfer hydrogen equally from both methyl groups. 

Phenylmenthyl esters are also suitable chiral groups for inducing stereoselectivity in radical addition reactions, as shown in the allylation of phenylmenthyloxycarbonyl-substituted xanthates. The photoinitiated reaction of the radical precursor with tributyl(2-propenyl)stannane at — 78 =C affords only one diastereomer4. The absolute configuration of (— )-8-phenylmenthyl 2-methyl-2-phenyl-4-pentenoate (5) is not known. 

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