Titanium tartrate asymmetric epoxidation, mechanism

Studies of bis-tartrate esters and other tartrate ligands for titanium-mediated asymmetric epoxidation have provided evidence against the sole intermediacy of monomeric titanium-tartrate species in the parent system329,330. Other tartrate ligands have been studied in attempts to gain a better understanding of the mechanism of the Sharpless epoxidation330. 

Transition metal-catalyzed epoxidations, by peracids or peroxides, are complex and diverse in their reaction mechanisms (Section 5.05.4.2.2) (77MI50300). However, most advantageous conversions are possible using metal complexes. The use of t-butyl hydroperoxide with titanium tetraisopropoxide in the presence of tartrates gave asymmetric epoxides of 90-95% optical purity (80JA5974). 

Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves, or with peroxy acids. Epoxidation of allylic alcohols can also be done with high enantioselectivity. In the Sharpless asymmetric epoxidation,allylic alcohols are converted to optically active epoxides in better than 90% ee, by treatment with r-BuOOH, titanium tetraisopropoxide and optically active diethyl tartrate. The Ti(OCHMe2)4 and diethyl tartrate can be present in catalytic amounts (15-lOmol %) if molecular sieves are present. Polymer-supported catalysts have also been reported. Since both (-t-) and ( —) diethyl tartrate are readily available, and the reaction is stereospecific, either enantiomer of the product can be prepared. The method has been successful for a wide range of primary allylic alcohols, where the double bond is mono-, di-, tri-, and tetrasubstituted. This procedure, in which an optically active catalyst is used to induce asymmetry, has proved to be one of the most important methods of asymmetric synthesis, and has been used to prepare a large number of optically active natural products and other compounds. The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound formed from the titanium alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the r-BuOOH. ... 

Review M. G. Finn and K. B. Sharpless, On the Mechanism of Asymmetric Epoxidation with Titanium-Tartrate Catalysts, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 5, Chap. 8, Academic Press, New York, 1985 R. A. Johnson and K. B. Sharpless, Addition Reactions with Formation of Car-... 

B. E. Rossiter (1985). Synthetic aspects and application of asymmetric epoxidation , in Asymmetric Synthesis. Ed. J. Morrison. Orlando Academic Press, p. 194 M. G. Finn and K. B. Sharpless On the mechanism of asymmetric epoxidation with titanium-tartrate catalysts . Ibid., p. 247. 

The mechanism of the asymmetric epoxidation of allylic alcohols with the Sharpless-Katsuki catalyst is assumed to be very similar to the one described for the Halcon-ARCO process in Section 2.5. The key point is that the chiral tartrate creates an asymmetric environment about the titanium center (Figure 18). When the allylic alcohol and the t-butyl hydroperoxide bind through displacement of alkoxy groups from the metal, they are disposed in such a way as to direct oxygen transfer to a specific face of the C=C double bond. This point is crucial to maximize enantioselectivity. 

MECHANISM OF THE TITANIUM TARTRATE CATALYZED ASYMMETRIC EPOXIDATION 420... 

The hallmark of titanium tartrate catalyzed asymmetric epoxidation is the high degree of enantiofacial selectivity seen for a wide range of allylic alcohols. The question naturally arises as to what is the mechanism of this reaction and what are the structural features of the catalyst that produce these desirable results. These questions have been studied extensively and the results have been the subject of considerable previous discussion. - d36 pg purpose of this chapter, we wish to review those aspects of the mechanistic-structural studies that may helpful in devising synthetic applications of this reaction. 

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

Finn MG, Sharpless KB (1985) On the mechanism of asymmetric epoxidation with titanium-tartrate catalysts. In Scott JW, Morrison JD (eds) Asymmetric Synthesis, vol 5. Academic Press, Orlando, p 247... 

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