8-Phenylmenthol esters

An 8-phenylmenthol ester was employed as the chiral auxiliary to achieve enantioselectivity in the synthesis of prostaglandin precursors.83 The crucial features of the TS are the anti disposition of the Lewis acid relative to the alcohol moiety and a tt stacking with the phenyl ring that provides both stabilization and steric shielding of the a-face. 

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%. ... 

Recendy, Darzens reaction was investigated for its synthetic applicability to the condensation of substituted cyclohexanes and optically active a-chloroesters (derived from (-)-phenylmenthol). In this report, it was found that reaction between chloroester 44 and cyclohexanone 43 provided an 84% yield with 78 22 selectivity for the axial glycidic ester 45 over equatorial glycidic ester 46 both having the R configuration at the epoxide stereocenter. 

Mainly sulfoxide groups are introduced as chiral auxiliaries for the modification of a,/J-unsat-urated enones (see Section D.1.5.3.5.). Chiral imine derivatives have also been used (see Section D.1.5.3.1.). Various chiral alcohols, and in particular 8-phenylmenthol, have been successfully used as auxiliaries, mainly in two-fold Michael additions to a,/ -unsaturatcd esters. 

Aldol reactions of 1 and 2 can be used to obtain any one of the four possible stereoisomers of a,3-dihydroxy esters.3 Thus 1 reacts with aldehydes to provide (2S)-aldols, and 2 reacts to provide (2R)-aldols. The syn/anti ratio of the aldols can be controlled by the choice of the enolate counterion. Thus lithium or magnesium enolates provide mainly an/i-aldols, whereas 5yn-aldols predominate with zirconium enolates. Ethanolysis of the purified adducts yields the optically pure a,p-dihydroxy esters without epimerization with recovery of 8-phenylmenthol. 

A highly diastereoselective aziridination of 8-phenylmenthol-derived a,ft -unsaturated esters (38) with 3-acetoxyamino-2-ethylquinazolinone (39) has been reported. The (g) yields of the resulting aziridines (40) were greatly improved in the presence of hexamethyldisilazane.51... 

Oxidation of chiral esters of phenylacetic acids. These esters can be converted into acetates of mandelic esters by oxidation with DDQ in acetic acid. The reaction is diastereoselective when carried out on esters of chiral alcohols, of which 8-phenylmenthol is the most useful. The presence of substituents on the phenyl group has slight effect on the diastereoselectivity, which depends on formation of a donor-acceptor complex between the substrate and the quinone with removal of a hydrogen atom. The acetoxy group then enters from the opposite, more bulky face. 

Starting from (R)-pulegone we present herein an efficient three-step synthesis furnishing (-)-phenylmenthol as an easily separable 87 13-mixture of diastereomers in 55-80% overall isolated yield. Separation of the two dlastereomers 1s achieved either by careful medium-pressure chromatography as Corey and Ensley stated, a,b or, less tediously for greater quantities, by fractional crystallization of the chloroacetic acid esters and successive saponification as described herein. 

Phenylmenthol (1), 11. 412-41.5. The material obtained from commercial ( + )-pule-gone by the original procedure of Corey and Ensley consists of (- )-8-phcnylmenthol and the Ci.Cfi-diastereomicr in the ratio 88 12. Separation of the pure reagent can be accomplished by column chromatography or, more conveniently, by cry.stallization of the 3,5-dinitrobenzoate ester, m.p. 119°, ao -217°. ... 

Asymmetric reactions of oc-keto esters of ( —)-l. Reduction of the a-keto ester (2) of (- )-8-phenylmenthol (1) with potassium triisopropoxyborohydride proceeds in 90% de to give the lactate ester (R)-3 with chirality opposite to that obtained by reaction of... 

This reaction of 1 with the optically active glyoxylate ester of 8-phenylmenthol provides an enantioselective synthesis of verrucarinolactone (3, equation II). 

Hydroperoxide-n-Butyllithium gives 50% de. Chiral 3-amino esters of 8-phenylmenthol have been prepared in 50-60% de by the addition of amines to the re face of 8-phenylmenthyl crotonate under 14-15 kbar pressures (eq 2). Much higher (75 to >99%) de is obtained using 8-0-naphthyl)menthol crotonate. The 3-amino esters obtained are of the proper configuration for conversion to biologically active 3-lactams. ... 

Tin(IV) Chloride-catalyzed ene reaction of the pyruvate ester of (—)-8-phenylmenthol with 1-hexene gives a single diastereomer of the unsaturated (S)-a-hydroxy ester (de>90%) (eq 3). Similarly, tin(I V) chloride-catalyzed ene reactions of 8-phenylmenthyl glyoxylates afford unsaturated secondary alcohols with 93-98% de of the (S) configuration. ... 

Glyoxalate esters of phenylmenthols (83 equation 20) have been extensively used as chiral auxiliaries for a number of different reactions. Selective Grignard addition from the nt face of the molecule... 

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