Homoallyl alcohols asymmetric epoxidation

Table 5.2 Asymmetric epoxidation of cis- and trans-allylic and homoallylic alcohols using poly(octamethylene tartrate)/Ti(Oz Pr)4/TBHP. 

Zrrconium(IV) and hafnium(IV) complexes have also been employed as catalysts for the epoxidation of olefins. The general trend is that with TBHP as oxidant, lower yields of the epoxides are obtained compared to titanium(IV) catalyst and therefore these catalysts will not be discussed iu detail. For example, zirconium(IV) alkoxide catalyzes the epoxidation of cyclohexene with TBHP yielding less than 10% of cyclohexene oxide but 60% of (fert-butylperoxo)cyclohexene °. The zirconium and hafnium alkoxides iu combiuatiou with dicyclohexyltartramide and TBHP have been reported by Yamaguchi and coworkers to catalyze the asymmetric epoxidation of homoallylic alcohols . The most active one was the zirconium catalyst (equation 43), giving the corresponding epoxides in yields of 4-38% and enantiomeric excesses of <5-77%. This catalyst showed the same sense of asymmetric induction as titanium. Also, polymer-attached zirconocene and hafnocene chlorides (polymer-Cp2MCl2, polymer-CpMCls M = Zr, Hf) have been developed and investigated for their catalytic activity in the epoxidation of cyclohexene with TBHP as oxidant, which turned out to be lower than that of the immobilized titanocene chlorides . ... 

Chiral alkenyl and cycloalkenyl oxiranes are valuable intermediates in organic synthesis [38]. Their asymmetric synthesis has been accomplished by several methods, including the epoxidation of allyl alcohols in combination with an oxidation and olefination [39a], the epoxidation of dienes [39b,c], the chloroallylation of aldehydes in combination with a 1,2-elimination [39f-h], and the reaction of S-ylides with aldehydes [39i]. Although these methods are efficient for the synthesis of alkenyl oxiranes, they are not well suited for cycloalkenyl oxiranes of the 56 type (Scheme 1.3.21). Therefore we had developed an interest in the asymmetric synthesis of the cycloalkenyl oxiranes 56 from the sulfonimidoyl-substituted homoallyl alcohols 7. It was speculated that the allylic sulfoximine group of 7 could be stereoselectively replaced by a Cl atom with formation of corresponding chlorohydrins 55 which upon base treatment should give the cycloalkenyl oxiranes 56. The feasibility of a Cl substitution of the sulfoximine group had been shown previously in the case of S-alkyl sulfoximines [40]. 

SCHEME 21. Asymmetric epoxidation of allylic and homoallylic alcohols. 

Stereoselective epoxidation of /i-cw-homoallylic alcohols by vanadium, tungsten and molybdenum oxo species has been used for the construction of intermediates with four adjacent asymmetric centres346. 

Stereoselective epoxidation. A detailed study of epoxidation of homoallylic alcohols with this system indicates that the direction and degree of stereoselectivity can be predicted from a vanadate ester transition state with the chair comformation A. for example, the selectivity is > 100 1 when R1 and R4 = H and R3 and R - alkyl, since 1,3-interactions are minimal. R1 can also be a methyl group, but the reaction is slowed. When R1 = isopropyl and R3 = methyl, severe 1,3-interactions in both chair forms result in low asymmetric induction (2 1 selectivity).2... 

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. 

The asymmetric epoxidation of homoallylic alcohols has continued to be a problematic area. A potential solution has recently been published <07JA286 07T6075>. The use of bis-hydroxamic acid 1 as a chiral ligand for a vanadium catalyst has provided both excellent yields and enantioselectivity. This method works well with both cis- and trans-alkenes. 

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... 

In contrast to allylic alcdiols, the asymmetric epoxidation of homoallylic alcohols shows the following three general characteristics (i) the rates of epoxidation are slower (ii) enantiofacial selectivity is reversed, i.e. oxygen is delivered to the opposite face of the alkene when the same tartrate ester is used and (iii) the of oiantiofacial selectivity is lower with enantiomeric excesses of the epoxy alcohols... 

Homoallylic alcohols can be asymmetrically epoxidized using a chiral vanadium catalyst equipped with the hydroxaraic acid ligand 45, as exemplified in Yamamoto s concise synthesis... 

The use of zirconium complexes derived from tartramides 3.19 in asymmetric epoxidation of homoallylic alcohols does not result in any improvement over the related to titanium analogs [808]. A zirconium complex prepared from Zr(Otert-Bu)4 and (S,S,S)-triisopropylam3ne 3.22 in the presence of water catalyzes the asymmetric ring opening of meso-epoxides by /-PiMe2SiN3 (ee 85%), while related titanium complexes are less efficient [805,831]. 

Scheme 4.7-16 Asymmetric epoxidation of a homoallylic alcohol using di(isopropyl)tar-taric acid (DIPT) as chiral ligand in liquid CO2 [79].

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