Enantiomers hydroperoxides

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

In light of the previous discussions, it would be instructive to compare the behavior of enantiomerically pure allylic alcohol 12 in epoxidation reactions without and with the asymmetric titanium-tartrate catalyst (see Scheme 2). When 12 is exposed to the combined action of titanium tetraisopropoxide and tert-butyl hydroperoxide in the absence of the enantiomerically pure tartrate ligand, a 2.3 1 mixture of a- and /(-epoxy alcohol diastereoisomers is produced in favor of a-13. This ratio reflects the inherent diasteieo-facial preference of 12 (substrate-control) for a-attack. In a different experiment, it was found that SAE of achiral allylic alcohol 15 with the (+)-diethyl tartrate [(+)-DET] ligand produces a 99 1 mixture of /(- and a-epoxy alcohol enantiomers in favor of / -16 (98% ee). 

The epoxidation of allylic alcohols can also be effected by /-butyl hydroperoxide and titanium tetraisopropoxide. When enantiomerically pure tartrate ligands are included, the reaction is highly enantioselective. This reaction is called the Sharpless asymmetric epoxidation.55 Either the (+) or (—) tartrate ester can be used, so either enantiomer of the desired product can be obtained. 

Sharpless epoxidation involves treating an allylic alcohol with titanium(IV) tetraisopropoxide [Ti(0-/Pr)4], tert-butyl hydroperoxide [t-BuOOH], and a specific enantiomer of a tartrate ester. 

A potentially powerful probe for sorting out the contribution of hydroperoxide-dependent and mixed-function oxidase-dependent polycyclic hydrocarbon oxidation is stereochemistry. Figure 9 summarizes the stereochemical differences in epoxidation of ( )-BP-7,8-dihydrodiol by hydroperoxide-dependent and mixed-function oxidase-dependent pathways (31,55,56). The (-)-enantiomer of BP-7,8-dihydrodiol is converted primarily to the (+)-anti-diol epoxide by both pathways whereas the (+)-enantiomer of BP-7,8-dihydrodiol is converted primarily to the (-)-anti-diol epoxide by hydroperoxide-dependent oxidation and to the (+)-syn-diol epoxide by mixed-function oxidases. The stereochemical course of oxidation by cytochrome P-450 isoenzymes was first elucidated for the methycholanthrene-inducible form but we have detected the same stereochemical profile using rat liver microsomes from control, phenobarbital-, or methyl-cholanthrene-induced animals (32). The only difference between the microsomal preparations is the rate of oxidation. 

In contrast, the HRP-catalyzed kinetic resolution of racemic secondary hydroperoxides in the presence of guaiacol afford the hydroperoxides and their alcohols in high enantiomeric excesses (Eq. 3) [69]. In the case of the aryl alkyl-substituted hydroperoxides and cyclic derivatives (Table 4, entries 1 -3,6-10), HRP preferentially accepts the (R)-enantiomers as substrates with concurrent formation of the (R)-alcohols the (S)-hydroperoxides are left behind, further-... 

The HRP also exhibits good to excellent enantioselectivities in the reduction of threo- and eryfhro-diastereomeric, hydroxy-functionalized hydroperoxides with preference for the (R)-configured enantiomers (Table 5). Very recently, dia-steromeric a, 0-hydroxy hydroperoxides (entries 6 and 15) were also resolved by HRP with high ee values. Moreover, the threo- and erythro-3-hydroperoxy-... 

The method with cumene hydroperoxide has been recently used with success,to prepare both enantiomers of methyl p-methoxyphenyl sulfoxide which were then taken as starting material for the total synthesis of biological compounds. 

In the case of diastereomeric mixtures of chiral hydroperoxides, standard chromatography on achiral phase can be employed to separate the diastereomers. As one example for the preparation of optically pure hydroperoxides via this method, the ex-chiral pool synthesis of the pinane hydroperoxides 11 is presented by Hamann and coworkers . From (15 )-cw-pinane [(15 )-cw-10], two optically active pinane-2-hydroperoxides cA-lla and trans-llb were obtained by autoxidation according to Scheme 17. Autoxidation of (IR)-c -pinane [(17 )-cw-10] led to the formation of the two enantiomers ent-lla and ent-llh. The ratio of cis to trans products was 4/1. The diastereomers could be separated by flash chromatography to give optically pure compounds. 

Kinetic resolution of racemic secondary hydroperoxides rac-16 can be effected by selective reduction of one enantiomer with employing either chiral metal complexes or enzymes (equation 10). In this way hydroperoxides 16 and the opposite enantiomer of the corresponding alcohols 19 can be produced in enantiomerically enriched form. As side products sometimes the corresponding ketones 20 are produced. 

In 1996, Hamann and Hoft were able to obtain 1,2,3,4-tetrahydronaphthyl hydroperoxide (THPO, 16b) in enantiomerically enriched form starting from the racemic mixture by selective decomposition of one enantiomer in the presence of Jacobsen s catalyst 21 . Besides the enantiomerically enriched hydroperoxide (5)-16b, also the corresponding alcohol (/f)-l-tetralol (19b) was isolated in enantiomerically enriched form (opposite... 

In this enzymatic transformation, three optically active compounds were prepared in one step. Besides the enantiomerically enriched hydroperoxide (5)-16/17a, also the opposite enantiomer of the corresponding alcohol (/f)-19/18a and enantiomerically enriched (S)-sulfoxide 23 could be isolated (equation 13). 

Table 17) with two substituents in position C3 the oxygen transfer by the chiral hydroperoxides occurred from the same enantioface of the double bond, while epoxidation of the (ii)-phenyl-substituted substrates 142c,g,i resulted in the formation of the opposite epoxide enantiomer in excess. In 2000 Hamann and coworkers reported a new saturated protected carbohydrate hydroperoxide 69b , which showed high asymmetric induction in the vanadium-catalyzed epoxidation reaction of 3-methyl-2-buten-l-ol. The ee of 90% obtained was a milestone in the field of stereoselective oxygen transfer with optically active hydroperoxides. Unfortunately, the tertiary allylic alcohol 2-methyl-3-buten-2-ol was epoxidized with low enantioselectivity (ee 18%) with the same catalytic system . 

Sharpless Asymmetric Epoxidation This is a method of converting allylic alcohols to chiral epoxy alcohols with very high enantioselectivity (i.e., with preference for one enantiomer rather than formation of racemic mixture). It involves treating the allylic alcohol with tert-butyl hydroperoxide, titanium(IV) tetra isopropoxide [Ti(0—/Pr)4] and a specific stereoisomer of tartaric ester. For example,... 

The oxygen that is transferred to the allylic alcohol to form epoxide is derived from tert-butyl hydroperoxide. The enantioselectivity of the reaction results from a titanium complex among the reagents that includes the enantiomerically pure tartrate ester as one of the ligands. The choice whether to use (+) or (-) tartrate ester for stereochemical control depends on which enantiomer of epoxide is desired. 

---