Homoallylic alcohols, Sharpless asymmetric

Asymmetric epoxidation of homoallylic alcohols. Sharpless asymmetric epoxidation of primary homoallylic alcohols with l-( + )-diethyl tartrate proceeds with only moderate enantiomeric selectivity (23-55% ee) and opposite to that observed with allylic alcohols. Unfortunately, operation at low temperatures to improve the enantiomeric excess also retards the rate drastically. Even so, this epoxidation provides a useful synthesis of (-l-)--y-amino-P(R)-hydroxybutyric acid (1). 

Optically active allylic alcohols and homoallylic epoxides. The reaction of optically active 2,3-epoxy halides (1), available by Sharpless asymmetric epoxidation of allylic alcohols, with a preformed mixture of vinylmagncsium bromide and Cul (2 equiv. each) in THF at —23° does not result as expected (7.H1-82) in a homoallylic epoxide, but... 

Corey, E. J., Guzman-Perez, A., Noe, M. C. The application of a mechanistic model leads to the extension of the Sharpless asymmetric dihydroxylation to allylic 4-methoxybenzoates and conformationally related amine and homoallylic alcohol derivatives. J. Am. Chem. Soc. 

Sharpless asymmetric epoxidation afforded epoxide 167 in 76% yield. Lindlar reduction, followed by oxidation with Collins reagent, yielded aldehyde 168. A Wittig reaction of aldehyde 168 with the ylide 169 gave the homoallylic alcohol 171 after deprotection of 170 under acidic conditions. Alcohol 171 was converted into the corresponding iodide and reacted with triphenylphosphine to provide phosphonium salt 172. 

Mechanistic studies on the Sharpless asymmetric epoxidation, Eq. (8), where DIPT is diisopropyl tartrate, have been published.The rate law in CH2CI2 is first-order in substrate, catalyst, and oxidant, and shows an inverse second-order dependence on the inhibiting alcohol, in this case Pr OH. This is consistent with a mechanism in which both substrate and the peroxide displace Pr O to form a key intermediate in the reaction. [Differences in the selectivities of allylic and homoallylic alcohols in this reaction have been exploited to invert the expected enantioselectivity. ... 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

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