Sharpless epoxidation

The Sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3-epoxyalcohols from primary and secondary allylic alcohols. The stereochemistry of the resulting epoxide is determined by the enantiomer of the chiral tartrate diester (usually diethyl tartrate or diisopropyl tartrate) employed in the reaction. The oxidizing agent is tert-butyl hydroperoxide. Enantioselectivity is achieved by a catalyst formed from titanium tetra(isopropoxide) and diethyl tartrate. Only 5–10 mol% of the catalyst in the presence of 3Å molecular sieves (3Å MS) is necessary. The success of the Sharpless epoxidation can be attributed to five major aspects. First, epoxides can be easily converted into diols, aminoalcohols, and ethers, so formation of chiral epoxides is important in the synthesis of natural products. Second, substrate scope is large, including many primary and secondary allylic alcohols. Third, the products of the Sharpless epoxidation frequently have enantiomeric excesses above 90%. Fourth, the products of the Sharpless epoxidation are predictable. Finally, the reactants for the Sharpless epoxidation are commercially available and relatively inexpensive. Several reviews have been published. K. Barry Sharpless shared the 2001 Nobel Prize in Chemistry for his work on asymmetric oxidations.The prize was shared with William S. Knowles and Ryōji Noyori. The structure of the catalyst is uncertain. Regardless, all studies have concluded that the catalyst is a dimer of The putative catalyst was determined using X-ray structural determinations of model complexes which have the necessary structural components to catalyze the Sharpless Epoxidation. The chirality of the product of a Sharpless epoxidation is sometimes predicted with the following mnemonic. A rectangle is drawn around the double bond in the same plane as the carbons of the double bond (the xy-plane), with the allylic alcohol in the bottom right corner and the other substituents in their appropriate corners. In this orientation, the (−) diester tartrate preferentially interacts with the top half of the molecule, and the (+) diester tartrate preferentially interacts with the bottom half of the molecule. This model seems to be valid despite substitution on the olefin. Selectivity decreases with larger R1, but increases with larger R2 and R3 (see introduction). However, this method incorrectly predicts the product of allylic 1,2-diols.