Chiral auxiliary also 8-phenylmenthyl

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). 

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... 

Introduction of chiral auxiliaries in the starting materials is very attract for applications to organic synthesis. However, to be of synthetic interest, chiral auxiliaries have to be inexpensive, readily introduced on the starting ma rial, inert in the conditions of irradiation, and readily removed from the photo ducts. Even if the first requirements can be easily satisfied with chiral ket esters, and amides, it is often difficult to avoid side reactions involving auxiliary [63]. In order to control all the asymmetric centers created in the in molecular photocycloadditions of cyclic enones with alkenes, esters of c alcohols were first considered. Although menthyl and bomyl derivatives ga only low de, 8-phenylmenthyl esters produced a far better asymmetric inducti [64]. The facial selectivity was found to depend on the syn/anti nature of t cycloadducts and the structure and location of the chiral auxiliary on either tl enone or the alkenyl moiety. More surprisingly the selectivity also depe strongly on the nature of the solvent (Scheme 21). 

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%. ... 

Phenylmenthol is also used as a chiral auxiliary in the reduction of several xan-thatesR. Standard radical reactions with tributyltin hydride at different temperatures yield the (-)-8-phenylmenthyl esters in moderate to good diastereomeric ratios. The bulk of the a-alkyl substituent shows a small influence on the selectivity. The absolute configuration of the products are assigned only for the (—)-8-phcnylmcnthyl 2-phenylpropanoate by reduction to the corresponding alcohols. 

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... 

Generally, arsonium ylides [62] are more reactive but less accessible than phos-phonium ylides. Recently, the chiral arsonium reagent 30 has appeared, and has been applied in asymmetric Wittig-type carbonyl olefinations. This first chiral arsonium reagent also bears 8-phenylmenthyl as a chiral auxiliary on its carboalkoxy portion [63], and gave moderate chemical yields and diastereoselectivities in the conversion of 4-substituted cyclohexanone derivatives to axially chiral non-racemic alkylidene cyclohexanes under the same reaction conditions as used for the related reactions with phosphorus reagents (Scheme 7.15). On the other hand, the corre-... 

Aluminum Lewis acid was also used in asymmetric radical addition of nucleophilic radical including alkyl radical to a,p-unsaturated carbonyls. Yonemitsu and CO workers reported diastereoselective radical cyclizationof alkynylacrylate equipped with 8-phenylmenthyl chiral auxiliary (Scheme 6.171) [201]. 

Aside from Coreys phenylmenthyl propanoate 424, several chiral enolates have been utilized for Michael additions with substantial degrees of diastereoselectiv-ity. Yamaguchi s group developed a series of chiral amide enolates 436 and studied the conjugate addition to crotonates [210]. Another remarkable early contribution came from Oppolzer and coworkers who used dienolate 437 for diastereoselec-tive consecutive additions to cyclopentenone and allylation [211]. The auxiliaries 436 and 437 served for total syntheses of terpenoid natural products. Diastereos-elective Michael additions were also achieved by means of imidazolidinone-based lithium enolate 438 [212] - another showcase of the efficiency of imidazolidinone 118 [54] (Scheme 4.94). 

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