Phenylmenthyl group

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). 

Fig. 11.19. Still-Gennari olefination of a racemic a-chi-ral aldehyde with an enan-tiomerically pure phosphonate as kinetic resolution I—Loss of the unreactive enantiomer ent-B of the aldehyde (R stands for the phenylmenthyl group in the Horner-Wadsworth-Emmons products the naming of the products in this figure is in agreement with the nomenclature of Figures 11.17 and 11.18).

The menthyl group has often been employed as an easily available chiral auxiliary. 8-Phenylmenthyl 2-amino-3,3-difluorocyclopentenecarboxylate 222 prepared from 219 via 221 was hydrogenated diastereoselectively to form ds-2-aminocarboxylate 223 (see Scheme 9.49) [77]. The higher diastereoselectivity induced by the 8-phenylmenthyl group was also observed in Znl2-catalyzed NaBH4 reduction of open-chain 3-amino-a, 3-unsaturated esters 224. In contrast, the unsubstituted menthyl ester was reduced with no practical diastereoselectivity (see table in Scheme 9.49). 

The diastereofacial selectivity of arylcarbenes has rarely been studied however, there are two reports dealing with enantioselective arylcarbene transfer. Addition of 9-diazofluorene to 2-propenoates or ( )-butendioates, which bear (—)-menthyl or (—)-8-phenylmenthyl groups as optically active auxiliaries, provides cyclopropanecarboxylates with moderate to very good diastcrcoselcctivities9. The best results are obtained with bis(8-phenylmenthyl) ( )-butene-dioate which affords the spiro compound with a d.r. of 95 5. Subsequent saponification and esterification with diazomethane leads to the corresponding spiro ir s[2,3]bis(methoxycarb-onyl)cyclopropane-l,9 -[9/f]-fluorene with 85% ee. 

Chiral esters of 1-carboxycyclopentene 172 with 3-methyl cyclohexenone 171 led to a mixture of cis-anti-cis stereoisomers with rather low diastereoselectivity [150]. Here also the phenylmenthyl group gave the highest diastereoselectivities and a decrease in the de with hydroxylic solvents was noticed. 

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... 

By using a chiral a-oximino ester, an efficient asymmetric induction at the y-position to the carbalkoxy group was noted with several hypervalent iodine reagents, this substrate gave products with varying degrees of yield and diastereo-isomeric selectivity, as illustrated in the following scheme, where R is (— )-8-phenylmenthyl [17] ... 

An excellent simple and induced selectivity could be obtained by Mulzer and his group [92] in the cycloaddition of 2-trimethylsilyl-oxy-l,3-pentadiene 2-31 and (lR,2S,5R)-8-phenylmenthyl glyoxylate 2-32 [93] in the presence of 0.2 equivalents of anhydrous MgBr2 in THF at 0 °C. After acidic workup the ketone 2-33 was isolated as a single diastereomer (>98%), which was then used for synthesis of the C-26-C-32 tetrahydropyran moiety of swinholide. In contrast,... 

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%. ... 

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. 

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. 

An excellent agreement between the d.r. (7/8) and the enantiomeric excess of the lactone 9 is shown for all auxiliaries. 8-Phenylmenthyl is the most effective chiral group in achieving asymmetric induction. It is assumed that the enoate 6a adopts the conformation shown in 10. The phenyl ring sterically blocks the C(a)-S7-face and consequently the photocycloaddition is directed predominantly to the C( )-Re-face to give the adduct 7a which on reduction led to lactone (+)-9. 

Allenes can also be employed (Scheme 11.61), as can alkenes, but the alkenes must be electron poor (Scheme 11.62). The cycloaddition is highly stereoselective, perhaps because the ester carbonyl group can act as a ligand for the chromium. High diastereoselectivity can be achieved with chiral auxiliaries (Scheme 11.63). The product 11.186 (R = (—)-8-phenylmenthyl) of the cycloaddition between complex... 

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