Enantioselective Epoxidation of Allylic Alcohols

SCHEME 13.111 Jung s total syntheses of 2,3-deoxy-3-substituted D-ribose derivatives. 

5-tetra-O-benzyl-D-arabinose 493, which is coupled with CrCl2 to benzyl a-(bromomethyl)-acrylate giving a 1 1 mixture of alcohols 494 and 495. Chromatographic separation and silylation followed by ozonolysis, hydrogenation and treatment with acid provides (+)-KDO. 

Certain transition metal complexes catalyze oxidation of allylic alcohols to the corresponding epoxides. The most useful procedures involve f-butyl hydroperoxide as 

The orientation of the reactants is governed by the chirality of the tartrate ester. The enantioselectivity can be predicted in terms of the model shown below. 

Finn and K. B. Sharpless in Asymmetric Synthesis, J. D. Morrison, ed., Vol 5, Academic Press, New York, 1985, Chap. 5. 

Visual models, additional information and exercises on the Sharpless Epoxidation can be found in the Digital Resource available at Springer.com/carey-sundberg. 

As with enantioselective hydrogenation, we see that several factors are involved in the high efficacy of the Ti(OiPr)4-tartrate epoxidation catalysts. The metal ion has two essential functions. One is the assembly of the reactants, the allylic alcohol, and the hydroperoxide. The second is its Lewis acid character, which assists in the rupture of the 0—0 bond in the coordinated peroxide. In addition to providing the reactive oxidant, the r-butyl hydroperoxide contributes to enantioselectivity through its steric bulk. Finally, the tartrate ligands establish a chiral environment that leads to a preference for one of the diastereomeric TSs and results in enantioselectivity. 

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Enantioselective epoxidation of allylic alcohols using t-butyl peroxide, titanium tetra-wo-propoxide, and optically pure diethyl tartrate. 

This method has proven to be an extremely useful means of synthesizing enantiomerically enriched compounds. Various improvements in the methods for carrying out the Sharpless oxidation have been developed.48 The reaction can be done with catalytic amounts of titanium isopropoxide and the tartrate ester.49 This procedure uses molecular sieves to sequester water, which has a deleterious effect on both the rate and enantioselectivity of the reaction. Scheme 12.9 gives some examples of enantioselective epoxidation of allylic alcohols. 

Enantioselective epoxidation of allylic alcohols using hydrogen peroxide and chiral catalysts was first reported for molybdenum 7B) and vanadium 79) complexe. In 1980, Sharpless 80) reported a titanium system. Using a tartaric acid derivative as chiral auxiliary it achieves almost total stereoselection in this reaction. 

Yamamoto has used the modularity of another type of oc-amino acid-based chiral ligand to promote enantioselective epoxidations of allylic alcohols [21]. Thus, as illustrated in Eq. (8), parallel libraries of various ligand candidates were prepared and the identity of the optimal ligand 13 was established through positional optimization. 

Chiral Mo complexes bearing ligands derived from a (2S,4R)- or (2S,4S)-4-hydroxyproline compound (13a and 13b) have been tethered to the internal surface of a mesoporous zeolite USY (251). The supported asymmetric Mo catalyst was tested for the enantioselective epoxidation of allylic alcohols. 

ENANTIOSELECTIVE EPOXIDATION OF ALLYLIC ALCOHOLS (2S,3S)-3-PR0PYL0XIRANEMETHAH0L (Oxiranemethanol, 3-Propyl-, (2S,3S)-)... 

A polyoxometalate is also at the heart of an enantioselective epoxidation of allylic alcohols using a C-2 symmetric chiral hydroperoxide 39 derived from l,l,4,4-tetraphenyl-2,3-0-isopropylidene-D-threitol (TADDOL). Thus, in the presence of the oxovanadium(IV) sandwich-type POM [ZnW(V0)2(ZnW9034)2]12- and stoichiometric amounts of hydroperoxide 39, the dienol 40 is converted to the (2R) epoxide 41 in 89% yield and 83% ee. The proposed catalytic cycle invokes a vanadium(V) template derived from the POM, substrate, and hydroperoxide, a hypothesis supported by the lack of enantioselectivity with unfunctionalized alkenes. The catalytic turnover is remarkably high at about 40,000 TON <03OL725>. 

Figure 2. Enantioselective epoxidation of allylic alcohols hy the Sharpless method...

Ti(OPr )4/Bu OOH/tartrate ester (Sharpless oxidation) (titanium isopropoxide/t-butyl hydroperoxide dialkyl tartrate) Dichloromethane -20 enantioselective epoxidation of allylic alcohols... 

The well-known Sharpless system for the enantioselective epoxidation of allyl alcohols has been investigated [23]. This system employs a tetra-alkoxy titanium precursor, a dialkyltartrate as an auxiliary, and an alkyl hydroperoxide as oxidant, to effect the enantioselective epoxidation. The key intermediate is thought to be a dimeric complex in which titanium is simultaneously coordinated to the chelating tartarate ligand, the substrate in the form of an oxygen bound / -allyl-oxide and an -tert-butylperoxide. 

W. Zhang, A. Basak, Y. Kosugi, Y. Hoshino, H. Yamamoto, Enantioselective epoxidation of allylic alcohols by a chiral complex of vanadium An effective controller system and a rational mechanistic model, Atigfiw. Chem. Int. Ed. Engl. 44 (2005) 4389. 

Enantioselective Epoxidation of Allylic Alcohols (Sharpless Reaction). . 69... 

In 1980, a highly enantioselective epoxidation of allylic alcohols was first reported by Katsuki and Sharpless [ 14]. This successful result was obtained by the use of a titanium-tartrate complex as the catalyst which has led by the following con-... 

Enantioselective epoxidation of allyl alcohols by means of titanium alkoxide, (+) or (-) diethyl tartarate (DET) and t-butyl hydroperoxide (TBHP). In the presence of molecular sieves, a catalytic amount of Ti alkoxide suffices7 (see 1st edition). 

The. V-alkylation of ephedrine is a convenient method for obtaining tertiary amines which are useful as catalysts, e.g., for enantioselective addition of zinc alkyls to carbonyl compounds (Section D. 1.3.1.4.), and as molybdenum complexes for enantioselective epoxidation of allylic alcohols (Section D.4.5.2.2.). As the lithium salts, they are used as chiral bases, and in the free form for the enantioselective protonation of enolates (Section D.2.I.). As auxiliaries, such tertiary amines were used for electrophilic amination (Section D.7.I.), and carbanionic reactions, e.g., Michael additions (Sections D. 1.5.2.1. and D.1.5.2.4.). For the introduction of simple jV-substituents (CH3, F.t, I-Pr, Pretc.), reductive amination of the corresponding carbonyl compounds with Raney nickel is the method of choice13. For /V-substituents containing further functional groups, e.g., 6 and 7, direct alkylations of ephedrine and pseudoephedrine have both been applied14,15. 

When bomeol or camphor is heated with solid potassium hydroxide to 250-280 °C, ring cleavage of the bicyclic system occurs and the product, campholic acid 68, can be isolated in high yield65-67. Thus, (-)-borneol gives ( + )-campholic acid [( + )-68], which has been used as the hydroxamic acid derivative as a chiral ligand for a vanadium catalyst in the enantioselective epoxidation of allylic alcohols (Section D.4.5.2.4.). 

The epoxidation reaction is normally best carried out with only 5-10 mol% of the titanium catalyst in the presence of activated molecular sieves. These conditions avoid the traditional use of stoichiometric catalyst and provide a mild and convenient method (although often at the expense of a slight reduction in enantioselectivity and rate of reaction). Numerous examples of highly enantioselective epoxidations of allylic alcohols by this procedure have been reported. For example, the allylic alcohol 44 was converted selectively into the epoxides 45 and 46 (5.56). 

Imido and 0x0 compounds are intermediates in many of the transfers of oxygen atoms and nitrene units to olefins to form epoxides and aziridines, and they are intermediates in many of the insertions of oxygen atoms and nitrene units into the C-H bonds of hydrocarbons to form alcohols and amine derivatives. The enantioselective epoxidation of allylic alcohols (Scheme 13.22) " is the most widely used epoxida-tion process, and the discovery and development of this process was one of the sets of chemistry that led K. Barry Sharpless to receive the Nobel Prize in Chemistry in 2001. The mechanism of this process is not well established, despite the long time since its discovery and development. Nevertheless, most people accept that transfer of the oxygen atom occurs from a titanium-peroxo complex - rather than from an 0x0 complex. Jacobsen s and Katsuki s - manganese-salen catalysts for the enantioselective epoxidations of unfunctionalized olefins, which were based on Kochi s achiral chromium- and manganese-salen complexes, are a second set of... 

If only one enantiomer is desired, then the methods we have learned for preparing epoxides will be inefficient, as half of the product is unusable and must be separated from the desired product. To favor formation of just one enantiomer, we must somehow favor epoxidation at one face of the alkene. K. Barry Sharpless, currently at the Scripps Research Institute, recognized that this could be accomphshed with a chiral catalyst. He reasoned that a chiral catalyst could, in theory, create a chiral environment that would favor epoxidation at one face of the alkene. Specifically, a chiral catalyst can lower the energy of activation for formation of one enantiomer more dramatically than the other enantiomer (Figme 14.2). In this way, a chiral catalyst favors the production of one enantiomer over the other, leading to an observed enantiomeric excess (ce). Sharpless succeeded in developing such a catalyst for the enantioselective epoxidation of allylic alcohols. An allylic alcohol is an alkene in which a hydroxyl group is attached to an allylic position. Recall that the aUyfic position is the position next to a C=C bond. 

Chiral catalysts can be used to achieve the enantioselective epoxidation of allylic alcohols. 

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