Alcohols, allylic with tert-butyl hydroperoxide

Natural compounds are also applied as chiral ligands in enantioselective homogeneous metallo-catalysts. A classical example is the Sharpless epoxidation of primary allylic alcohols with tert-butyl hydroperoxide [37]. Here the diethyl ester of natural (R,R)-(+)-tartaric acid (a by-product of wine manufacture) is used as bi-dentate ligand of the Ti(iv) center. The enantiomeric excess is >90%. The addition of zeolite KA or NaA is essential [38], bringing about adsorption of traces of water and - by cation exchange - some ionization of the hydroperoxide. 

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 existence of a facile epoxidation of II at a more rapid rate than that of TME is of interest in relation to a possible intermolecular pathway for formation of an epoxy alcohol from an allylic hydroperoxide during olefin oxidation. When a solution of II (0.01 mole) in TME (0.09 mole) was treated with tert-butyl hydroperoxide (0.01 mole) in the presence of... 

The retarding effect of alcohols on the rate of epoxidation manifests itself in the observed autoretardation by the alcohol coproduct.428,434 446,447 The extent of autoretardation is related to the ratio of the equilibrium constants for the formation of catalyst-hydroperoxide and catalyst-alcohol complexes. This ratio will vary with the metal. In metal-catalyzed epoxidations with fe/T-butyl hydroperoxide, autoretardation by tert-butyl alcohol increased in the order W < Mo < Ti < V the rates of Mo- and W-catalyzed epoxidations were only slightly affected. Severe autoretardation by the alcohol coproduct was also observed in vanadium-catalyzed epoxidations.428 434 446 447 The formation of strong catalyst-alcohol complexes explains the better catalytic properties of vanadium compared to molybdenum for the epoxidation of allylic alcohols.429 430 452 On the other hand, molybdenum-catalyzed epoxidations of simple olefins proceed approximately 102 times faster than those catalyzed by vanadium.434 447 Thus, the facile vanadium-catalyzed epoxidation of allyl alcohol with tert-butyl hydroperoxide may involve transfer of an oxygen from coordinated hydroperoxide to the double bond of allyl alcohol which is coordinated to the same metal atom,430 namely,... 

Asymmetric epoxidation Is accomplished by reaction of an allylic alcohol with tert-butyl hydroperoxide In the presence of J)-(-) or L-(+)-dlethyl tartrate and titanium tetralsopropoxlde (Figure la). The orientation of the product can be predicted in advance (-) tartrates epoxldize from the top face of the double bond when the bond Is viewed In a horizontal plane and the carbinol group is on the right, as seen from the front of the plane. The (+) tartrates epoxldize from below the plane (Figure lb). 

Molybdenum hexacarbonyl, Mo(CO)6 [328], and molybdenum ace-tylacetonate, Mo02(acac)2 [530], catalyze the stereoselective epoxidation of allylic alcohols with tert-butyl hydroperoxide. 

Allylic alcohols, for example geraniol, 2-methylallyl alcohol, 3,3-dimethylallyl alcohol, 3-buten-2-ol, l-octen-3-ol, and l-hexen-3-ol, are epoxidized with tert-butyl hydroperoxide in the presence of a vanadyl salen oxo-transfer catalyst in supercritical CO2. The metal catalyst was prepared in a simple two-step, Schiff base-type reaction to form the salen ligand, followed by complexation to the vanadyl group. The use of non-toxic supercritical CO2 in the presence of the new epoxidation vanadium catalyst led to yields and diastereoselectivities that were comparable to those resulting from the use of environmentally hazardous solvents such as CH2CI2 [59]. 

Alternatively, an enantiomerically pure catalyst that is not an enzyme can be used to obtain an enantiomerically pure target molecule. For example, an enantiomerically pure epoxide of an allylic alcohol can be prepared by treating the alcohol with tert-butyl hydroperoxide, titanium isopropoxide, and enantiomerically pure diethyl tartrate (DET). The structure of the epoxide depends on the enantiomer of diethyl tartrate used. 

Asymmetric epoxidation ranks as one of the most reliable and selective methods for the formation of single enantiomer products. In particular, the asymmetric epoxidation of allylic alcohols with tert-butyl hydroperoxide (t-BuOOH),... 

Together with hydrogenation and isomerization, epoxidation completes the trio of commercially significant applications of enantioselective homogeneously catalyzed reactions. Stereospecific olefin epoxidation is distinctive in that it creates two chiral centers simultaneously. The enantioselective epoxidation method developed by Sharpless and co-workers is an important asymmetric transformation known today. This method involves the epoxidation of allylic alcohols with tert.-butyl hydroperoxide and titanimn isopropoxide in the presence of optically active pure tartrate esters (Eq. 3-14). 

Sharpless epoxidation (Section 16.9) Allylic alcohols are converted to epoxides by treatment with tert-butyl hydroperoxide and titanium(IV) alkoxides. The reaction is highly enantioselective in the presence of enantiomerically pure diethyl tartrate. 

Alnminium alkoxides have long been used as catalysts for the reduction of aldehydes or ketones by secondary alcohols and recently lanthanide alkoxides were reported to act similarly in addition to catalysing the epoxidation of allylic alcohols with tert-butyl hydroperoxide. Aluminium alkoxides have also been used to catalyse the conversion of aldehydes to alkylesters (Tischtchenko reaction). A review gives a fascinating account of the use of heterometal alkoxides in asymmetric catalysis. 

In 1980, K. B. Sharpless (then at the Massachusetts Institute of Technology, presently at The Scripps Research Institute) and co-workers reported a method that has since become one of the most valuable tools for chiral synthesis. The Sharpless asymmetric epoxidation is a method for converting allylic alcohols (Section 11.1) to chiral epoxy alcohols with very high enan-tioselectivity (i.e., with preference for one enantiomer rather than formation of a racemic mixture). In recognition of this and other work in asymmetric oxidation methods (see Section 8.16A), Sharpless received half of the 2001 Nobel Prize in Chemistry (the other half was awarded to W. S. Knowles and R. Noyori see Section 7.14). The Sharpless asymmetric epoxidation involves treating the allylic alcohol with tert-butyl hydroperoxide, titanium(IV) tetraisopropoxide [Ti(0—/-POJ, and a specific stereoisomer of a tartrate ester. (The tartrate stereoisomer that is chosen depends on the specific enantiomer of the epoxide desired). The following is an example ... 

Among the thousands of enantioselective reactions now known, one of the most general is the so-called Sharpless epoxidation, in which an allylic alcohol, such as geraniol, is treated with tert-butyl hydroperoxide, (CHajaC—OOH, in the presence of titanium tetraisopro-poxide and diethyl tartrate (DET) as a chiral auxiliary reagent. When the (R,R) tartrate is used, geraniol is converted into its 2R,3S epoxide with 98% selectivity. 

Sharpless epoxidation (Chapter 19 A Deeper Look) A method for enantioselective synthesis of a chiral epoxide by treatment of an allylic alcohol with tert-butyl hydroperoxide, (013)30—OOH, in the presence of titanium tetraisopropoxide and diethyl tartrate. 

The great synthetic versatility of epoxides has prompted intense efforts to identify reliable enantioselective methods for their synthesis [71]. In 1980, this challenge was met as Sharpless announced the groundbreaking discovery that titanium-tartrate complexes in combination with tert-butyl hydroperoxide readily catalyze enantioselective epoxidations of allylic alcohols [72]. This transformation has rightly earned its prominent place in the history of organic chemistry and asymmetric catalysis. In subsequent investigations it was found that the addition of molecular sieves to the reaction mixture had a beneficial effect on the process. Consequently, under optimal conditions the epoxidation reaction can be performed with only 5-10 mol % of the readily available Ti catalyst [73, 74]. A wide variety of allylic alcohols can be epox-... 

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 activity of the FePeCli6-S/tert-butyl hydroperoxide (TBHP) catalytic system was studied under mild reaction conditions for the synthesis of three a,p-unsaturated ketones 2-cyclohexen-l-one, carvone and veibenone by allylic oxidation of cyclohexene, hmonene, and a-pinene, respectively. Substrate conversions were higher than 80% and ketone yields decreased in the following order cyclohexen-1-one (47%), verbenone (22%), and carvone (12%). The large amount of oxidized sites of monoterpenes, especially limonene, may be the reason for the lower ketone yield obtained with this substrate. Additional tests snggested that molecular oxygen can act as co-oxidant and alcohol oxidation is an intermediate step in ketone formation. 

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. 

The scope of metal-mediated asymmetric epoxidation of allylic alcohols was remarkably enhanced by a new titanium system introduced by Katsuki and Sharpless epoxidation of allylic alcohols using a titanium(IV) isopropoxide, dialkyl tartrate (DAT), and TBHP (TBHP = tert-butyl-hydroperoxide) proceeds with high enantioselectivity and good chemical yield, regardless of... 

In 1980, Katsuki and Sharpless[1] reported that, with the combination of a titanium(IV) alkoxide, an enantiomerically pure tartrate ester [for example (+)-diethyl tartrate ((+)-DET) or (+) di-iso-propyltartrate ((+)-DIPT)] and tert-butyl hydroperoxide, they were able to carry out the epoxidation of a variety of allylic alcohols in good yield and with a good enantiomeric excess (Figure 5.1). 

Dogterom P, Nagelkerke JF, van Steveninick J, et al. 1988. Inhibition of lipid peroxidation by disulfiram and diethydithiocarbamate does not prevent hepatotoxin-induced cell death in isolated rat hepatocytes. A study with allyl alcohol, tert-butyl hydroperoxide, diethyl maleate, bromoisovalerylurea and carbon tetrachloride. Chem Biol Interact 66 251-265. 

Both the ally lie alcohol and tert-hutyX hydroperoxide are achiral, but the product epoxide is formed in high optical purity. This is possible because the catalyst, titanium tetraiso-propoxide, forms a chiral (possibly dimeric [36]) complex with resolved diethyl tartrate [(+)-DET] which binds the two achiral reagents together in the reactive complex. The two enantiotopic faces of the allylic double bond become diastereotopic in the chiral complex and react at different rates with the tert-butyl hydroperoxide. Many other examples may be found in recent reviews [31, 37-39]. 

To probe hydroperoxide reactivity in these systems we studied the reaction of tert-butyl hydroperoxide in the presence of [C5H5V(CO)4]. In contrast to the rhodium(I) and molybdenum complexes, [C5H5V-(CO)4] catalyzed the rapid decomposition of tert-butyl hydroperoxide to oxygen and tert-butyl alcohol in both toluene and TME (Table II). When reaction was done by adding the hydroperoxide rapidly to the vanadium complex in TME, no epoxide (I) was produced. However, when the TME solution of [C5H5V(CO)4] was treated with a small amount (2-3 times the molar quantity of vanadium complex) of tert-butyl hydroperoxide at room temperature, a species was formed in situ which could catalyze the epoxidation of TME. Subsequent addition of tert-butyl hydroperoxide gave I in 13% yield (Table II). This vanadium complex also could catalyze the epoxidation of the allylic alcohol (II) to give tert-butyl alcohol and IV (Reaction 14). Reaction 14 was nearly quantitative, and the reaction rate was considerably faster than with TME. 

The exceptionally facile epoxidation of allylic alcohols by tert-butyl hydroperoxide in the presence of vanadium catalysts, discussed earlier, has been used466,467 for the synthesis of complex molecules. Thus, geraniol (X) and linalool (XI) are selectively epoxidized to the previously unknown monoepoxides with f-Bu02 H-V 0(acac)2 466 ... 

The Cr-PILC catalyzed benzylic and allylic oxidations also provide a facile approach to the oxidative deprotection of allyl and benzyl ethers and amines. Treatment of allyl or benzyl ethers with one equivalent of tert-butyl hydroperoxide in the presence of Cr-PILC at room temperature resulted in the oxidative cleavage of the allyl- or benzyl-oxygen bond to give the alcohol but when two equivalents of tert-butyl hydroperoxide (TBHP) were used, the alcohol was oxidized further to the aldehyde or ketone (Eqn. 21.21).47 Oxidation of allyl amines resulted in the cleavage of the allyl-nitrogen bond to give the des-allyl amine.47 Benzyl amines, however, were oxidized to the benzamides (Eqn. 21.22).45... 

The formation of 3-methyl-2-buten-l-ol, 4, and of 3-methyl-2-butenal, 5, in some experiments can be related to the isomerization of la and subsequent oxidation of product 4, thus formed, to 5. We observed that the vanadium oxo-alkoxide, [OV(OC3H7)3], is a good precursor for the catalytic epoxidation of substrates la, lb and Ic with systems involving tert-butyl hydroperoxide and tertiary allylic alcohols. These systems proved to be more active than those involving [VO(acac)2] usually associated with anhydrous r-BuOOH in benzene or toluene (Figure 1 and Table 2). 

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