8-PHENYLMENTHOL ,

Harada, N. Ochiai, N. Takada, K. Uda, H. Chem. CommunJJ. Chem. Soc., Chem. Commun. 1977, 495. 

Solladie-Cavallo, A. Solladie, G. Tsamo, E. Inorg. Synth. 1985,2S, 85. 

Solladie-Cavallo, A. Farkhani, D. Dreyfuss, A. C. Sanch, F. Bull. Soc. Chem. Fr. Part 2 1986, 906. 

Franck-Neumann, M. Martina, D. Heitz, M. P. J. Organomet. Chem. 1986,301,61. 

Guy Solladie Franfoise Colobert University Louis Pasteur, Strasbourg, France 

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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. 

Lewis acid-mediated asymmetric Diels-Alder reactions between 2H-azirines 59, bearing chiral auxiliaries, with enophiles such as 60 afforded mixtures of bicyclic aziridine-2-carboxylates 61 (Scheme 3.20) [68]. 8-Phenylmenthol appeared to be the auxiliary of choice in this reaction in terms of yield and diastereoselectivity. 

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. 

Alkenylcarbene complexes react with in situ-generated iodomethyllithium or dibromomethyllithium, at low temperature, to produce cydopropylcarbene complexes in a formal [2C+1S] cycloaddition reaction. This reaction is highly diastereoselective and the use of chiral alkenylcarbene complexes derived from (-)-8-phenylmenthol has allowed the enantioselective synthesis of highly interesting 1,2-disubstituted and 1,2,3-trisubstituted cyclopropane derivatives [31] (Scheme 9). As in the precedent example, this reaction is supposed to proceed through an initial 1,4-addition of the corresponding halomethyllithium derivative to the alkenylcarbene complex, followed by a spontaneous y-elimi-nation of lithium halide to produce the final cydopropylcarbene complexes. 

The reaction of alkenylcarbene complexes and imines in the presence of a Lewis acid generates pyrroline derivatives as a result of a [3C+2S] cyclisation process [76]. This reaction has been extended to an asymmetric version by the use of chiral alkenylcarbene complexes derived from several chiral alcohols. However, the best results are found when (-)-8-phenylmenthol-derived complexes are used and catalytic amounts of Sn(OTf)2 are added to the reaction. In these conditions high levels of trans/cis selectivity are achieved and the hydrolysis of the major tram diastereoisomers allows the preparation of optically pure 2,5-disubstituted-3-pyrrolidinone derivatives (Scheme 29). 

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. 

Substituted 3-hydroxy-2-pyrrolidinones were synthesised via 1,3-DC reactions of furfuryl nitrones with acrylates and subsequent intramolecular cyclisation after N-0 bond reduction. Addition of iV-acryloyl-(2/()-bomane-10,2-sultam to Z-nitrone 83 gave the endo/exo cycloadducts in 85 15 ratio with complete stereoface discrimination <00JOC1590>. The 1,3-DC of pyrroline A-oxide to chiral pentenoates using (-)-/rans-2-phenylcyclohexanol and (-)-8-phenylmenthol as chiral auxiliaries occurred with moderate stereocontrol (39% de and 57% de, respectively) and opposite sense of diastereoselectivity <00EJO3595>. The... 

Application of the above method to chiral 2-en-7-ynoates derived from optically active 8-phenylmenthol led to asymmetric ring-closure to give bicydic ketones bearing an angular substituent, with high ee values, as shown in Eq. 9.64, s.p. 349 [112]. 

A satisfactory result was obtained with the ligand 4 [43], which was synthesized from neo-menthol and contains an equatorial cyclopentadienyl group. The enantioselectivity of the opening attained synthetically useful levels (97 3) and the isolated yields were reasonable. Complex 5 [44], incorporating a ligand derived from phenylmenthone, also performed well. An enantioselectivity of 96.5 3.5 was observed. Phenylmenthol has already been extensively and successfully used as a chiral auxiliary [45]. 

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. 

Taguchi and coworkers175 studied the Lewis acid catalyzed asymmetric Diels-Alder reactions of chiral 2-fluoroacrylic acid derivatives with isoprene and cyclopentadiene. When a chiral l,3-oxazolidin-2-one and diethylaluminum chloride were used as the chiral auxiliary and the Lewis acid catalyst, respectively, a de of 90% was observed for the reaction with isoprene. The reaction with cyclopentadiene afforded a 1 1 mixture of endo and exo isomers with de values of 95% and 96%, respectively. The endo/exo selectivity was improved by using 8-phenylmenthol as the chiral auxiliary. Thus, the reaction... 

The chiral TV-sulfmylcarbamate 248 derived from 8-phenylmenthol formed a mixture of two epimeric cycloadducts 249 and 250 with cyclohexa-1,3-diene (equation 132)124, whereas the reaction with (E, )-hexa-2,4-diene in the presence of tin(IV) chloride gave solely the epimer 251 (equation 133)125. 

In the course of examining the CAI effect of conformational restriction of the C3-side-chain, intermediate 24 was prepared. Shankar and co-workers (Shankar et al., 1996) demonstrated that 10, a key intermediate in the research synthesis could be accessed by Wacker oxidation of olefin 24 (Scheme 13.7). Additionally, an alternative chiral variant of the well-precedented addition of zinc enolates to imines was demonstrated. Treatment of the bromoacetate 25, derived from 8-phenylmenthol with zinc and sonication followed by imine addition afforded 26 in 55% yield with greater than 99% de. Ethyl magnesium promoted ring-closure followed by C3 alkylation with 28, intercepts the previously demonstrated route through formation of olefin 24 (Shankar et al., 1996). 

Phenylmenthol. The preparation of 8-phenylmenthol (1) according to Corey and Ensley (11, 412) results in formation also of the diastereomer (2) that is epimeric at both Ci and C2 and hence named 2-ep/,enf-8-phenylmenthol. These products are... 

Diels-Alder reaction Cyclopentadiene, 78 Menthol, 172 8-Phenylmenthol, 243 Ene reaction 8-Phenylmenthol, 243 Epoxidation... 

Morpholino)acrylonitrile, 195 Oxygen, singlet, 228 Phenyl ethylenesulfonate, 241 8-Phenylmenthol, 243 (Phenylsulfonyl)allene, 247 Sulfene, 68... 

Di-2-pyridyl thionocarbonate, 127 Formaldehyde, 136 Iodomethyltrimethylsilane, 315 Palladium(II) acetate, 232 Tributyl(iodomethyl)tin, 314 Ene reaction Ethylaluminum dichloride, 5 Oxygen, singlet, 228 8-Phenylmenthol, 243 Zinc bromide, 349 Enol acylation... 

Diiodomethane-Diethylzinc, 276 2-Oxazolidones, chiral, 267 8-Phenylmenthol, 243 (S)-Prolinol, 261 Simmons-Smith reagent, 275 L-Valinol, 341 Amides... 

Methyl-5-phenyl-3-(3-phenylpro-pionyl)-2-oxazolidone, 24 (S)-l-[l-Methyl-2-pyrrolidinyl]-methylpiperidine, 116, 302 Methyl p-tolyl sulfoxide, 115 Norephedrine, 200 2-Oxazolidones, chiral, 24, 225, 267 (2R,4R)-Pentanediol, 205, 237 /r[Pg.403]

Since the conversion of (-)-citronellol to (S)-pulegone is reported, the enantiomeric (+)-8-phenylmenthol likewise may be synthesized. The latter should also be obtainable in a seven-step synthesis starting from (R)-pulegone (48% overall yield) as Corey and co-workers claimed.3 ... 

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