Sharpless asymmetric epoxidation stereoselectivity

A cuprate prepared in situ from tBuPh2SiLi and Cul has been found to react with alkynyl epoxides to afford allenylsilanes (Eq. 9.43) [50]. Enantioenriched alkynyl epoxides, which are readily prepared in high yield through Sharpless asymmetric epoxidation [51], afford chiral allenylsilanes with anti stereoselectivity. 

The chapter on alicyclic stereoselection has been splitted in two chapters (9 and 10). Chapter 10, which is exclusively devoted to Sharpless asymmetric epoxidation and dihydroxylation, has been rewritten de novo. The most recent advances in catalytic and stereoselective aldol reactions are incorporated in Chapter 9. 

Asymmetric epoxidation, dihydroxylation, aminohydroxylation, and aziridination reactions have been reviewed.62 The use of the Sharpless asymmetric epoxidation method for the desymmetrization of mesa compounds has been reviewed.63 The conformational flexibility of nine-membered ring allylic alcohols results in transepoxide stereochemistry from syn epoxidation using VO(acac)2-hydroperoxide systems in which the hydroxyl group still controls the facial stereoselectivity.64 The stereoselectivity of side-chain epoxidation of a series of 22-hydroxy-A23-sterols with C(19) side-chains incorporating allylic alcohols has been investigated, using m-CPBA or /-BuOOH in the presence of VO(acac)2 or Mo(CO)6-65 The erythro-threo distributions of the products were determined and the effect of substituents on the three positions of the double bond (gem to the OH or cis or trans at the remote carbon) partially rationalized by molecular modelling. 

The known allylic alcohol 9 derived from protected dimethyl tartrate is exposed to Sharpless asymmetric epoxidation conditions with (-)-diethyl D-tartrate. The reaction yields exclusively the anti epoxide 10 in 77 % yield. In contrast to the above mentioned epoxidation of the ribose derived allylic alcohol, in this case epoxidation of 9 with MCPBA at 0 °C resulted in a 65 35 mixture of syn/anti diastereomers. The Sharpless epoxidation of primary and secondary allylic alcohols discovered in 1980 is a powerful reagent-controlled reaction.12 The use of titanium(IV) tetraisopropoxide as catalyst, tert-butylhydro-peroxide as oxidant, and an enantiopure dialkyl tartrate as chiral auxiliary accomplishes the epoxidation of allylic alcohols with excellent stereoselectivity. If the reaction is kept absolutely dry, catalytic amounts of the dialkyl tartrate(titanium)(IV) complex are sufficient. 

A Sharpless asymmetric epoxidation features in a synthesis of (S)-chromanethanol (15). In the key cyclisation step, the absolute configuration of the diol is retained by a double inversion (95SL1255). trans-6-Cyano-2,2-dimethylchroman-3,4-diol is obtained from the racemic diol with excellent optical purity by the stereoselective acylation using Candida cylindraceae lipase (95TA123). 

The Swem oxidation is widely used to convert terminal alcohols into the corresponding aldehydes. Reaction of dimethyl l-(methoxycarbonyl)methylphosphonate with butadienemonoepoxide in the presence of 5% Pd(PPh,)4 furnishes the dimethyl 5-hydroxy-l-methoxycarbonyl-3-pente-nylphosphonate in a highly regio- and stereoselective manner in fair yields. After a Sharpless asymmetric epoxidation, the alcohol is submitted to a Swem oxidation, which produces dimethyl l-methoxycarbonyl-3,4-epoxy-4-formylbutylphosphonate in good yield (Scheme 5.51). Diethyl... 

The ether derivatives 0,0,0-trimethylkorupensamine A (248) and B have both been synthesised by a route which commenced with a lengthy sequence to the biaryl 249 from 3,5-dimethylanisole (ref. 95) (Scheme 32). Reduction of 249 with LiAlHa and oxidation gave aldehyde 250 which upon Wadsworth-Emmons-Homer extension, reduction and Sharpless asymmetric epoxidation provided epoxide 251 and the corresponding atropisomer in almost equal amounts which were separated by silica gel chromatography. The derived alcohol 252, obtained by mesylation of 251 and in situ reduction, was then converted into the acetamide 253 by displacement with azide under Mitsunobu conditions followed by reduction and acetylation. Ring closure followed by stereoselective reduction then yielded 0,0,0-trimethylkorupensamine A (248). The synthesis of 0,0,0-triraethylkorupensamine B was accomplished in a similar manner using the atropisomer of 251 obtained in the epoxidation step. 

The Sharpless asymmetric epoxidation method has been used with great success for the synthesis of 2,6-dideoxyhexoses and an enormous range of alditols. Unfortunately, it is not possible to do full justice to this work in this review however, it is worth noting that after the Ti -mediated asymmetric epoxidation the products can be reduced in a highly stereoselective fashion using sodium bis(methoxyetho7Qr)aluminium hydride (Red-al). ... 

Figure 11.30 Application of Sharpless asymmetric epoxidation in the stereoselective synthesis of N-Boc-(2S,3S)-[3- H 4- C Ivaline...

The emergence of the powerful Sharpless asymmetric epoxida-tion (SAE) reaction in the 1980s has stimulated major advances in both academic and industrial organic synthesis.14 Through the action of an enantiomerically pure titanium/tartrate complex, a myriad of achiral and chiral allylic alcohols can be epoxidized with exceptional stereoselectivities (see Chapter 19 for a more detailed discussion). Interest in the SAE as a tool for industrial organic synthesis grew substantially after Sharpless et al. discovered that the asymmetric epoxidation process can be conducted with catalytic amounts of the enantiomerically pure titanium/tartrate complex simply by adding molecular sieves to the epoxidation reaction mix-... 

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