Alcohols titanium-catalyzed epoxidation

SCHEME 70. Titanium-catalyzed epoxidation of ene-diols 145 by, 6-hydroperoxy alcohols 148... 

This approach provides a new method for carbohydrate synthesis. In the synthesis of tetritols, pentitols, and hexitols, for example, titanium-catalyzed asymmetric epoxidation and the subsequent ring opening of the thus formed 2,3-epoxy alcohols can play an essential role. 

SCHEME 59. Titanium-catalyzed asymmetric epoxidation of both enantiomers of aUyUc alcohol 39j... 

In 2003, Lattanzi and coworkers reported on the use of the tertiary camphor-derived hydroperoxide 61 in the titanium-catalyzed asymmetric epoxidation of allylic alcohols (equation 39f. Yields were moderate and ranged between 30 and 59%. Also, the enantio-selectivities obtained were only moderate (24-46%). After the reaction, the enantiomeri-cally pure camphor-derived alcohol can be recovered in good yields by chromatography without loss of optical purity and can be reconverted into the corresponding hydroperoxide. 

The literature has been reviewed through 1989 for the purposes of preparing this chapter but the documentation herein is not intended to be comprehensive. Other reviews have covered various aspects of asymmetric epoxidation including synthetic applications through 1984, a thorough compilation of uses through early 1987 and an extensive discussion of the mechanism of the reaction. Use of homochiral epoxy alcohols in the synthesis of polyhydroxylated compounds, e.g. sugars, and for the preparation of various synthetic intermediates has been reviewed.A personal account of the discovery of titanium-catalyzed asymmetric epoxidation has been recorded." A comprehensive review of titanium-catalyzed asymmetric epoxidation is planned."... 

This section presents a summary of the currently preferred conditions fw perfrmning titanium-catalyzed asymmetric epoxidations and is derived primarily from the detailed account of Gao et al We wish to draw the reader s attention to several aspects of the terminology used here and throughout this chapter. The terms titanium tartrate complex and titanium tartrate catalyst are used interchangeably. The term stoichiometric reaction refers to the use of the titanium tartrate complex in a stoichiometric ratio (100 mol %) relative to the substrate (allylic alcohol). The term catalytic reaction (or quantity) refers to the use of the titanium tartrate complex in a catalytic ratio (usually S-10 mol %) relative to the substrate. 

The essence of titanium-catalyzed asynunetric epoxidation is illustrated in Figure 1. As shown there, the four essential components of the reaction are tiie allylic alcohol substrate, a titanium(IV) alkoxide, a chiral tartrate ester and an alkyl hydroperoxide. The asynunetric complex formed from these reagents de-... 

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. 

Epoxidation of allylic alcohols with peracids or hydroperoxide such as f-BuOaH in the presence of a transition metal catalyst is a useful procedure for the synthesis of epoxides, particularly stereoselective synthesis [587-590]. As the transition metal catalyst, molybdenum and vanadium complexes are well studied and, accordingly, are the most popular [587-590], (Achiral) titanium compounds are also known to effect this transformation, and result in stereoselectivity different from that of the aforementioned Mo- and V-derived catalysts. The stereochemistry of epoxidation by these methods has been compared for representative examples, including simple [591] and more complex trcMs-disubstituted, rrans-trisubstituted, and cis-trisubstituted allyl alcohols (Eqs (253) [592], (254) [592-594], and (255) [593]). In particular the epoxidation of trisubstituted allyl alcohols shown in Eqs (254) and (255) highlights the complementary use of the titanium-based method and other methods. More results from titanium-catalyzed diastereoselective epoxidation are summarized in Table 25. 

Ti(0-/-Pr)4-catalyzed epoxidation works for allyl alcohols with an electron-deficient olefin. The epoxidation of different allyl alcohols bearing an electron-withdrawing group has been attested [596-599] and Eq. (257) compares the stereochemical outcome of a few methods of epoxidation [596]. The titanium-based method generally results in considerable improvement of syn selectivity. The stereoselectivity of the reaction depicted by Eq. (258) is the reverse of that afforded by alkaline peroxide epoxidation [599]. 

Although these reactions obviously involve intramolecular oxygen transfer within a titanium(IV) tartrate-ally lie alcohol-alkyl hydroperoxide complex, analogous to the vanadium-catalyzed epoxidations discussed above, the exact nature of the catalytic species and the mechanism of enantioselection remain controversial [39, 40],... 

General Aspects of Titanium-Catalyzed Asymmetric Epoxidation of Primary Allylic Alcohols... 

Katsuki-Sharpless asymmetric epoxidation. Since its introduction in 1980 [10], the Katsuki-Sharpless asymmetric epoxidation (AE) reaction of allylic alcohols has been one of the most popular methods in asymmetric synthesis ([11-14]). In this work, the metal-catalyzed epoxidation of allylic alcohols described in the previous section was rendered asymmetric by switching from vanadium catalysts to titanium ones and by the addition of various tartrate esters as chiral ligands. Although subject to some technical improvements (most notably the addition of molecular sieves, which allowed the use of catalytic amounts of the titanium-tartrate complex), this recipe has persisted to this writing. 

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