Epoxides Sharpless reagent

Sharp less asymmetric epoxidation (Section 12.15) An enantioselec-tive oxidation reaction that converts the double bond of an aUyUc alcohol to a predictable enantiomeiicaUy enriched epoxide. Sharpless reagent (Section 12.15) The reagent used in the Sharpless asymmetric epoxidation. The Sharpless reagent consists of tert-butyl hydroperoxide, a titanium catalyst, and one enantiomer of diethyl tartrate. 

Asymmetric epoxidation of racemic unsaturated fluoro alcohols by the chiral Sharpless reagent can be exploited for kmetic resolution of enantiomers The recovered stereoisomer has 14-98% enantiomeric excess [55] (equation 50)... 

Sesquinorbornatrienes 949 Sharpless asymmetric epoxidation 826 Sharpless reagent 73, 289, 291 Shift reagents, coordination of sulphoxides with 573... 

TABLE 4-1. Asymmetric Epoxidation of Allylic Alcohols by Sharpless Reagents (Method A) and by the Modified Sharpless Reagents (Method B)... 

Conditions Method A Epoxidation using Sharpless reagent method B addition of 0.05-0.1 equivalent of calcium hydride and 0.1-0.15 equivalent of silica gel to the Sharpless reagent, ee = Enantiomeric excess. 

In the Sharpless epoxidation of divinylmethanols only one of four possible stereoisomers is selectively formed. In this special case the diastereotopic face selectivity of the Sharpless reagent may result in diastereomeric by-products rather than the enantiomeric one, e.g., for the L,-(+)-DIPT-catalyzed epoxidation of (E)-a-(l-propenyl)cyclohexanemethanol to [S(S)-, [R(S)-, [S(R)- and [R(R)-rrans]-a-cyclohexyl-3-methyloxiranemethanol the ratio of rate constants is 971 19 6 4 (see above S.L. Schreiber, 1987). This effect may strongly enhance the e.e. in addition to the kinetic resolution effect mentioned above, which finally reduces further the amount of the enantiomer formed. 

Let s take these three chiral synthons in turn. First, the simplest one the central epoxide. The reagent we need here will carry a leaving group, such as a tosylate, and it can easily be made from the epoxy-alcohol. This gives a very good way of making this compound as a single enantiomer—a Sharpless asymmetric epoxidation of ally] alcohol. 

Chiral sulfoxides. The Sharpless reagent lor asymmetric epoxidation also effects asymmetric oxidation of prochiral sulfides to sulfoxides. The most satisfactory results are obtained for the stoichiometry Ti(0-(-Pr)4/L DET/H20/(CH,),C00H = 1 2 1 2 for I equiv. of sulfide. In the series of alkyl p-tolyl sulfides, the (R)-sulfoxide is obtained in 41-90% ee the enantioselectivity is highest when the alkyl group is methyl. Methyl phenyl sulfide is oxidized to the (R)-sulfoxide in 81% ee. Even optically active dialkyl sulfoxides can be prepared in 50-71% ee the enantioselectivity is highest for methyl octyl sulfoxide. 

It has also been found that addition of a catalytic amount of calcium hydride and silica gel to the Sharpless reagent can greatly reduce the reaction time for asymmetric epoxidation of an allylic alcohol. The time saving is often a factor of 10 or 15, and always at least a foctor of 3. ... 

The identity of the DET isomer determines which enantiomer is the major product obtained in the epoxidation of an allylic alcohol with the Sharpless reagent. 

Problsrin 12.30 Explain why only one 0=0 of geraniol is epoxidized with the Sharpless reagent. 

Epoxidation of the following allylic alcohol using the Sharpless reagent with (-)-DET gives two epoxy alcohols in a ratio of 87 13. 

Key Words Ethylene oxide, Propylene oxide. Epoxybutene, Market, Isoamylene oxide. Cyclohexene oxide. Styrene oxide, Norbornene oxide. Epichlorohydrin, Epoxy resins, Carbamazepine, Terpenes, Limonene, a-Pinene, Fatty acid epoxides, Allyl epoxides, Sharpless epoxidation. Turnover frequency, Space time yield. Hydrogen peroxide, Polyoxometallates, Phase-transfer reagents, Methyltrioxorhenium (MTO), Fluorinated acetone, Alkylmetaborate esters. Alumina, Iminium salts, Porphyrins, Jacobsen-Katsuki oxidation, Salen, Peroxoacetic acid, P450 BM-3, Escherichia coli, lodosylbenzene, Oxometallacycle, DFT, Lewis acid mechanism, Metalladioxolane, Mimoun complex, Sheldon complex, Michaelis-Menten, Schiff bases. Redox mechanism. Oxygen-rebound mechanism, Spiro structure. 2008 Elsevier B.V. 

For allylic alcohols, use the Sharpless asymmetric epoxidation reaction. Reagents are t-BuOOH, Ti(Oi-Pr)4 and (-l-)-diethyl (or di-isopropyl) tartrate. Note that the (-1-)-enantiomer of the ligand is required for the formation of the epoxide 6 (place the alcohol in the lower right using the model given in Scheme 5.55). 

Kinetic resolution of secondary allylic alcohols by Sharpless asymmetric epoxidation using fert-butylhydroperoxide in the presence of a chiral titanium-tartrate catalyst has been widely used in the synthesis of chiral natural products. As an extension of this synthetic procedure, the kinetic resolution of a-(2-furfuryl)alkylamides with a modified Sharpless reagent has been used . Thus treatment of racemic A-p-toluenesulphonyl-a-(2-furfuryl)ethylamine [( )-74] with fert-butylhydroperoxide, titanium isopropoxide [Ti(OPr-/)4], calcium hydride (CaHa), silica gel and L-(+)-diisopropyl tartrate [l-(+)-DIPT] gave (S)-Al-p-toluenesulphonyl-a-(2-furfuryl)ethylamine [(S)-74] in high chemical yield and enantiomeric excess . Similarly prepared were the (S)-Al-p-toluenesulphonyl-a-(2-furfuryl)-n-propylamine and other homologues of (S)-74 using l-(+)-D1PT. When D-(—)-DIPT was used, the enantiomers were formed . ... 

The Sharpless epoxidation of allylic alcohols by hydroperoxides uses as mediator [45] or as catalyst [46] a chiral titanium complex obtained from the combination Ti(OPr )4/diethyl tartrate (DET) in 1 1 ratio. Kinetic resolution of P-hydroxysulfides was also observed, but without diastereoselectivity for the product P-hydroxysulfoxides [47]. We found that the Sharpless reagent deactivated by 1 equivalent of water allows the enantioselective oxidation of aryl methyl sulfides into sulfoxides to be performed with ee s up to 90% [4S-50]. The best reagent combination proved to be Ti(0Pr )4/DET/H20 = 1 2 1. Independently, Modena et al. obtained similar enantioselectivities with the combination Ti(OPr )4/DET in 1 4 ratio [51]. These two combinations are sometimes referred to as the Kagan reagent and the Modena reagent, respectively. They will be considered successively. 

Jacobsen Epoxidation, Sharpless Dihydroxyiation (Bristol-Myers Squibb). Both, Jacobsen and Sharpless methodology were applied for making multikilogram amounts of benzofuran epoxide, an intermediate for a melatonin antagonist (82). Both reactions required extensive optimization of reagents and reaction conditions. 

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