8-Phenylmenthyl esters

Table 1.8 Use of 8-phenylmenthyl esters to induce asymmetry in the Darzens reaction.

Ohkata [30, 31] and co-workers have employed an 8-phenylmenthyl ester to induce asymmetry in the Darzens reaction (Table 1.8). Moderate to high diaster-... 

The formation of spirocyclopropanes from the reaction of diazodiphenylmethane and ( )-8-phenylmenthyl esters of acrylic acid and methyl fumarate occurred with a modest level of diastereofacial selectivity (136). In contrast, diastereoselectivities of 90 10 were achieved in the cycloadditions of diazo(trimethylsilyl)methane with acrylamides 65 derived from camphor sultam as the chiral auxiliary (137) (Scheme 8.16). Interestingly, the initial cycloadducts 66 afforded the nonconjugated A -pyrazolines 67 on protodesilylation the latter were converted into optically active azaproline derivatives 68. In a related manner, acrylamide 69 was converted into A -pyrazolines 70a,b (138). The major diastereoisomer 70a was used to synthesize indolizidine 71. The key step in this synthesis involves the hydrogenolytic cleavage of the pyrazoline ring. 

Diastereoselectivity in the (3 + 2) photocycloaddition of di-( )-menthyl, di-( )-8-phenylmenthyl, and di-( )-bomyl derivatives (398b-d) is largely dependent on the concavity of the auxiliary, steric bulk of the substituents of the alkenes, and reaction temperature [365] (Scheme 107). The highest de value was obtained when 8-phenylmenthyl ester 398c was employed, although the yield of the adducts was relatively low. The bomyl ester 398d showed poor diastereoselectivity. The effect of the chiral auxiliary seems to be reasonably explained in terms of the concavity of the auxiliary. When a-methylstyrene was used as the alkene, two stereoisomers of (3 + 2) adducts were obtained in lower yields than... 

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). 

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. 

Michael additions with 8-phenylmenthyl esters of unsaturated acids Chiral auxiliaries attached elsewhere in asymmetric Michael additions Other Chiral Auxiliaries in Conjugate Addition The Evans oxazolidinones Chiral sulfoxides Asymmetric Birch Reduction Birch reduction of benzene Asymmetric Birch reduction of heterocycles... 

Michael additions with 8-phenylmenthyl esters of unsaturated acids... 

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. 

Chiral auxiliaries are capable of controlling the absolute steric course of radical reactions. 8-Phenylmenthyl ester or an amide derived from Oppolzer s camphor sultam can be utilized for enantioselective ring closure to cyclopentane, the chiral auxiliary directing the addition to the alkene. The reductive radical cyclization of 8-phenylmenthyl 2-phenylthio-6-heplenoale at 80 °C gives four isomeric cyclopentane derivatives in an overall yield of 90 % 3. The reaction proceeds with modest cis irons ratio, but a considerably higher RiS selectivity of 80 20. 

The next example shows a diastereoselective alkylation of a chiral Schiff base derived from glycine114. The A A -cyclohexylsulfamoylisobornyl derivative exhibits best diastereoselectivi-ties, whereas menthol or 8-phenylmenthyl esters are less selective. 

The auxiliary-mediated [2,3] Wittig rearrangement of nonracemic allyloxy acetates has to date received little attention. Enolates of the 8-phenylmenthyl esters 42 (R1 = CH3, Bu) undergo [2,3] rearrangement with good syn selectivity (>90%) and comparable levels of induced diastereose-lection85. 

R)-2-Deuterioglycine is obtained in a diastereomeric ratio of 90 10 via a similar reaction sequence starting from the (-)-8-phenylmenthyl ester of 2,2-dideuterioglycine12. 

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. 

Reductive cyclization of ta-ethynyl a,P-unsaturated esters. The Lewis acid-catalyzed radical cyclization is subject to 1,3-asymmetric induction by the chiral moiety of the ester. Thus (-)-8-phenylmenthyl esters give mainly the 2-methylene-cycloalkylacetic esters of (R) configuration. 

A new synthesis of L-apiose uses the photochemical reaction of the (-)-8-phenylmenthyl ester of phenylglyoxylic acid with 2,2-di-methyl-1,3-dioxalen to generate the oxetan (18) with 96% d.e., leading in turn to the branched-chain sugar (19) and the apioside (20)(Scheme 7). ... 

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... 

The fluorination of 8-phenylmenthyl esters with 2 proceeded in poor yield but with a higher diastereoselectivity compared to other fluorinating agents (eq 9). ... 

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