Epoxy-alcohol product

In 1980, Katsuki and Sharpless described the first really efficient asymmetric epoxidation of allylic alcohols with very high enantioselectivities (ee 90-95%), employing a combination of Ti(OPr-/)4-diethyl tartrate (DET) as chiral catalyst and TBHP as oxidant Stoichiometric conditions were originally described for this system, however the addition of molecular sieves (which trap water traces) to the reaction allows the epoxidation to proceed under catalytic conditions. The stereochemical course of the reaction may be predicted by the empirical rule shown in equations 40 and 41. With (—)-DET, the oxidant approaches the allylic alcohol from the top side of the plane, whereas the bottom side is open for the (-l-)-DET based reagent, giving rise to the opposite optically active epoxide. Various aspects of this reaction including the mechanism, theoretical investigations and synthetic applications of the epoxy alcohol products have been reviewed and details may be found in the specific literature . 

In situ derivatization of the crude epoxy alcohol product becomes a viable alternative to isolation when 5-10 mol % of catalyst is used for the epoxidation. This procedure is especially useful when the product is reactive or is difficult to isolate because of solubility in an aqueous extraction phase [15,16]. Low-molecular-weight epoxy alcohols such as glycidol are readily extracted from the reaction mixture after conversion to ester derivatives such as the p-nitrobenzoate or 3-nitrobenzenesulfonate [4,17]. This derivatization not only facilitates isolation of the product but also preserves the epoxide in a synthetically useful form. 

The concentration of substrate used in the asymmetric epoxidation must be given consideration because competing side reactions may increase with increased reagent concentration. The use of catalytic quantities of the Ti-tartrate complex has greatiy reduced this problem. The epoxidation of most substrates under catalytic conditions may be performed at a substrate concentration up to 1 M. By contrast, epoxidations using stoichiometric amounts of complex are best run at substrate concentrations of 0.1 M or lower. Even with catalytic amounts of the complex, a concentration of 0.1 M may be maximal for substrates such as cinnamyl alcohol, which produce sensitive epoxy alcohol products [4]. 

Ti(IV) isopropoxide [Chemical Abstracts nomenclature 2-propanol, Ti(4+) salt], is the Ti species of choice for preparation of the Ti-tartrate complex in the asymmetric epoxidation process. The use of Ti(IV) f-butoxide has been recommended for reactions in which the epoxy alcohol product is particularly sensitive to ring opening by the alkoxide [18]. The 2-substituted epoxy alcohols are one such class of compounds. Ring opening by f-butoxide is much slower than by i-propoxide. With the reduced amount of catalyst that now is sufficient for all asymmetric epoxidations, the use of Ti(0-f-Bu)4 appears to be unnecessary in most cases, but the concept is worth noting. 

Both the synthetic 3 and mechanistic 1 aspects of this asymmetric epoxidatlon process have been reviewed recently. While the process has great scope regarding the allylic alcohol substrate, there are two classes of substrates which present difficulties. These limitations will be best appreciated by reference to the recent reviews however, the main problems are worth mentioning here. When difficulties arise, they are almost never due to the failure of the asymmetric epoxidatlon process Itself, but can be traced instead to the nature of the epoxy alcohol product. 

M or lower. Even with catalytic amounts of the complex, a concentration of 0.1 M may be maximal for substrates, such as cinnamyl alcohol, which produce sensitive epoxy alcohol products. ... 

Chang, M.S., W.E. BoegUn, F.P. Guengerich, and A.R. Brash, Cytochrome P450-Depen-dent Transformations of 15R- and 15iS-Hydroperoxyeicosatetraenoic Acids Stereoselective Formation of Epoxy Alcohol Products, Biochemistry 35 464—471 (1996). 

An alternate pathway available to however, is intramolecular radical attack on the peroxide linkage (10,11) yielding ultimately the epoxy-alcohol product. We wished to investigate this Sfli pathway systematically and sought other, more controlled methods for the preparation of radicals like... 

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