Epoxidation Sharpless titanium catalyzed

Asymmetric epoxidation. Sharpless et a .1 have reviewed the numerous applications of titanium-catalyzed asymmetric epoxidations developed in their own and other laboratories. All the reactions conform to the enantiomeric selectivity first observed and formulated as in Scheme (I). 

There are many synthetic applications of epoxide formation. Titanium alkoxides in the presence of diethyltartrate as a chiral ligand catalyze the epoxidation of allylic alcohols enantioselectively (Sharpless reaction). In the presence of singlet... 

K. Barry Sharpless and Tsutomu Katsuki Titanium-catalyzed asymmetric epoxidation... 

The original report32 of the titanium-catalyzed asymmetric epoxidation of allylic alcohols in 1980 has been followed by hundreds of applications, the majority of which use the initially reported conditions. In the decade since the introduction of this reaction numerous improvements have been made41. The most complete discussion of the preparative aspects of both the asymmetric epoxidation and the kinetic resolution was presented by the Sharpless group42. This paper details the effects of reagent stoichiometry and concentration, substrate concentration, aging of the catalyst and variation of oxidant, solvent and tartrate as well as workup procedures. What is particularly noteworthy in this presentation is that significant amounts of unpublished work are drawn upon to develop recommendations for successful reaction. 

Sharpless compares the discovery of a new and a more effective catalyst to a fishing expedition for a rare fish. If one looks at the number of metals that are capable of catalyzing olefin epoxidation (these include Sc, Ti, V, Cr, Y, Zr, Nb, Mo, La, Hf, Ta, W, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, and U), it is indeed a fishing expedition. The coelacanth for Sharpless turned out to be the metal titanium his distinction, in part, involved titanium-catalyzed oxidation of olefins using the organic oxidant, /-butylhydroperoxide. We will look at a smaller catch—perhaps a cod—VO(acac)2, which Sharpless and his co-worker Michaelson discovered on an earlier fishing... 

K.B. Sharpless, in "The Discovery of Titanium Catalyzed Asymmetric Epoxidation", Chemtech, November (1985) 692. 

One of the most useful organic reactions discovered in the last several decades is the titanium-catalyzed asymmetric epoxidation of primary aUyUc alcohols developed by Professor Barry Sharpless, then at Stanford University. The reagent consists of tert-butyl hydroperoxide, titanium tetraisopropoxide [Ti(0-iPr)J, and diethyl tartrate. Recall from Section 3.4B that tartaric add has two chiral centers and exists as three stereoisomers a pair of enantiomers and a meso compound. The form of tartaric add used in the Sharpless epoxidation is either pure (+)-diethyl tartrate or its enantiomer, (-)-diethyl tartrate. The fert-butyl hydroperoxide is the oxidizing agent and must be present in molar... 

In 1990, Choudary [139] reported that titanium-pillared montmorillonites modified with tartrates are very selective solid catalysts for the Sharpless epoxidation, as well as for the oxidation of aromatic sulfides [140], Unfortunately, this research has not been reproduced by other authors. Therefore, a more classical strategy to modify different metal oxides with histidine was used by Moriguchi et al. [141], The catalyst showed a modest e.s. for the solvolysis of activated amino acid esters. Starting from these discoveries, Morihara et al. [142] created in 1993 the so-called molecular footprints on the surface of an Al-doped silica gel using an amino acid derivative as chiral template molecule. After removal of the template, the catalyst showed low but significant e.s. for the hydrolysis of a structurally related anhydride. On the same fines, Cativiela and coworkers [143] treated silica or alumina with diethylaluminum chloride and menthol. The resulting modified material catalyzed Diels-Alder reaction between cyclopentadiene and methacrolein with modest e.s. (30% e.e.). As mentioned in the Introduction, all these catalysts are not yet practically important but rather they demonstrate that amorphous metal oxides can be modified successfully. 

A major advantage that nonenzymic chiral catalysts might have over enzymes, then, is their potential ability to accept substrates of different structures by contrast, an enzyme will select only its substrate from a mixture. Striking examples are the chiral phosphine-rhodium catalysts, which catalyze die hydrogenation of double bonds to produce chiral amino acids (10-12), and the titanium isopropoxide-tartrate complex of Sharpless (11,13,14), which catalyzes the epoxidation of numerous allylic alcohols. Since the enantiomeric purities of the products from these reactions are exceedingly high (>90%), we might conclude... 

Sharpless asymmetric epoxidation of allylic alcohols, asymmetric epoxidation of conjugated ketones, asymmetric sulfoxidations catalyzed, or mediated, by chiral titanium complexes, and allylic oxidations are the main classes of oxidation where asymmetric amplification effects have been discovered. The various references are listed in Table 4 with the maximum amplification index observed. 

Epoxy alcohols. A few years ago Mihelich1 was granted a patent for preparation of epoxy alcohols by photooxygenation of alkenes in the presence of titanium or vanadium catalysts. Adam et al.2 have investigated this reaction in detail and find that Ti(IV) isopropoxide is the catalyst of choice for epoxidation of di-, tri-, and tetrasubstituted alkenes, acyclic and cyclic, to provide epoxy alcohols. When applied to allylic alcohols, the reaction can be diastereo- and enantioselective. The reaction actually proceeds in two steps an ene reaction to provide an allylic hydroperoxide followed by intramolecular transfer of oxygen catalyzed by Ti(0-i-Pr)4. The latter step is a form of Sharpless epoxidation and can be highly stereoselective. 

Sharpless, K. B., Woodard, S. S., Finn, M. G. On the mechanism of titanium-tartrate catalyzed asymmetric epoxidation. PureAppl. Chem. 1983, 55, 1823-1836. 

Summing up, a short review about the methods of enantioselective epoxidation with peroxidic reagents has been given. In the forefront of the discussion there was the titanium/tartrate-catalyzed asymmetric epoxidation discovered by Katsuki and Sharpless, which is characterized by simplicity, reliability, and high enantio-selectivity, but also by well-defined limits. Moreover, I have tried to include some results obtained in this field by our group adding them to the knowledge of asymmetric epoxidation. 

Titanium-pillared montmorillonites (Ti-PILC) modified with tartrates were described as heterogeneous Sharpless epoxidation catalysts [33] as well as for the oxidation of aromatic sulfides [34]. Metal oxides modified with histamine showed modest efficiencies for the kinetic resolution of activated amino acid esters (kj /k5 2) [35]. Silica or alumina treated with diethylaluminium chloride and menthol catalyzed the Diels-Alder reaction between cylopentadiene and methacrolein with modest enantioselectivities of up to 31% ee [36]. ZeoHte HY, modified with chiral sulfoxides had remarkable selectivities for the kinetic resolution of 2-butanol (k /kj =39) but unfortunately the catalyst is not very stable... 

Among the reactions catalyzed by titanium complexes, the asymmetric epoxidation of allylic alcohols developed by Sharpless and coworkers [752, 807-810] has found numerous synthetic applications. Epoxidation of allylic alcohols 3.16 by ferf-BuOOH under anhydrous conditions takes place with an excellent enantioselectivity (ee > 95%) when promoted by titanium complexes generated in situ from Ti(0/ -Pr)4 and a slight excess of diethyl or diisopropyl (R,R)- or (iS, 5)-tartrates 2.69. The chiral complex formed in this way can be used in stoichiometric or in catalytic amounts. For catalytic use, molecular sieves must be added. Because both (RJ )- and (5,5)-tartrates are available, it is posable to obtain either enantiomeric epoxide from a single allylic alcohol. Cumene hydroperoxide (PhCMe20OH) can also be used in place of ferf-BuOOH. This method has been applied to industrial synthesis of enantiomeric glycidols [811, 812]. 

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