Sharpless epoxidation

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The Sharpless epoxidation is a name reaction in synthetic organic chemistry. It belongs to the group of catalytic asymmetric reactions. Starting from prochiral compounds can be formed selectively only one enantiomer of the product; it is an enantio-and diastereoselective reaction. The reaction affords 2,3- epoxy alcohols from allylic alcohols. These products contain both epoxy and alcohol groups and can be used as starting materials for the synthesis of numerous other substances.

Barry Sharpless won the Nobel Prize in Chemistry, which he shared with William S. Knowles and Ryoji Noyori for the study of asymmetric oxidation reactions in 2001.

Reaction conditions

Typically, the Sharpless epoxidation is carried out at -78 ° C in dichloromethane. The substrate is a primary or secondary allyl alcohol. The oxidizing agent is a hydroperoxide, usually tert- butyl hydroperoxide. The complex, which induced the stereoselectivity is formed from catalytic amounts added titanium ( IV) isopropylalkoholat ( titanium (IV ) isopropoxide, 5 to 10 mol %) and the enantiomerically pure tartaric acid diethyl ester ( diethyl [ DET ], 6 to 12 mol %). The addition of molecular sieves ( 3 Å, or 4 ) decreases the amount of the catalyst, surprisingly, that must be used.

You put in -78 ° C cold dichloromethane, molecular sieve, titanium isopropoxide and tartrate before, stirred for a while, and then tert -butyl hydroperoxide and the substrate. After the reaction is quenched with weak acid, a reducing solution. Is suitable for this example, iron ( II ) chloride and tartaric acid in water. The iron reduces peroxides, while the tartaric acid titanium complex and can lead to the aqueous phase. Strongly acidic work-up can lead to the epoxide.

Mechanism

Enantioselective epoxidation proceeds starting from an achiral / prochiral starting material ( allyl alcohol ) with the aid of a chiral catalyst consisting of DET and titanium (IV) isopropoxide ( titanium tetraisopropoxide ).

To this end, with two equivalents of isopropanol is first liberated from titanium ( IV) isopropoxide and the optically active diethyl tartrate, in the example ( S, S), which generates most likely present as a dimer chiral catalyst. The two remaining residues are substituted isopropoxide and allyl alcohol in the following reaction sequence by the oxidizing agent (tert- butylhydroperoxide ), whereby a "complex" of chiral catalyst, allyl alcohol and epoxidation results. This complex has a preferred geometry. The titanium (IV ) alkoxide species acts as a Lewis acid by coordinately binds the O ² atom, and thus the remaining Peroxosauerstoffatom electrophile. The Peroxosauerstoffatom is added to the double bond. After aqueous work-up (hydrolysis), the (2R )-epoxide and t-butanol is obtained. Alternatively, leads to the (2S )-epoxide by using (R, R)- diethyl tartrate.

Alternative reactions

Since the Sharpless epoxidation limited exclusively to allylic alcohols, ordinary, non-functionalized olefins ( alkenes) can alternatively be implemented by the Jacobsen - Katsuki epoxidation with optically active Mn ( III ) complexes or the Shi epoxidation with potassium peroxomonosulfate to epoxides ( oxiranes ) be.