Epoxidation of homoallylic alcohols

In a recent paper, Zhang and Yamamoto have described a modified BHA ligand (235d) that is suitable for highly enantioselective vanadium-catalyzed epoxidation of homoallylic alcohols (Scheme 102). Both tram- and cA-substituted epoxides were achieved with nearly complete enantioselectivities and good yields. 

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 . ... 

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... 

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. 

Rationalise the diastereoselectivity observed in the epoxidation of homoallylic alcohol 5. How could the stereoselectivity of this reaction be reversed ... 

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). 

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... 

Enantioselective Epoxidations of Homoallylic Alcohols by Metal Tartramides... 

As discussed in the preceeding section, the application of the Sharpless method to the epoxidation of homoallylic alcohols leads to epoxy alcohols with only 23-55% enantiomeric excess and of opposite steric course relative to that observed for allylic alcohols. The reason for the low enantioselection was considered to be due to steric congestion in the chain of the homoallylic alcohol as it folded to come into contact with the peroxygen. 

Novel chiral vanadium-bishydroxamic acid complexes have been used to catalyze the enantioselective epoxidation of homoallylic alcohols <2007JA286>. Yields and enantioselectivities are excellent. 

Roush s three-carbon chain-elongation method applied to 2,3-O-cyclohexylidene-D-glyceralde-hyde (R)-62 is an efficient approach to D-glucitol derivatives, which relies on the vyfx-selective epoxidation of homoallylic alcohol 170 (Scheme 13.59) [105,107]. 

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]. 

Diamides of tartaric acid with primary amines have been used as chiral ligands for titanium-and zirconium-catalyzed epoxidations of homoallylic alcohols by the Sharpless method (Section D.4.5.2.4.). Such diamides are conveniently obtained from dimethyl or diethyl tartrate by reaction with the corresponding amine38. The iV,A A, /V -tetrarnethyl diamide has been used for the formation of chiral dioxolanes (Section D.1.5.1.) and in the synthesis of chiral alkenes (Section D.l.6.1.5.). 

The stereochemistry of epoxidation of homoallylic alcohols has been established by reduction of the products with AIH4. The structure of resulting diols (334) and (335) demonstrates that the original peroxy-acid attack had occurred from the same side of the double bond as the OH group further peroxy-acid oxidation of (334) occurred from the opposite side owing to... 

Zhang W, Yamamoto H. Vanadium-catalyzed asymmetric epoxidation of homoallylic alcohols. J. Am. Chem. Soc. 2007 129 286-287. 

SCHEME 35.6. Asymmetric epoxidation of homoallylic alcohols catalyzed by vanadium-chiral-hydroxamic-acid complexes. 

SCHEME 35.8. Asymmetric epoxidation of homoallylic alcohol 29 in the synthesis of ( )-a-hisaholol. 

General experimental procedure for Yamamoto epoxidation of homoallylic alcohols To a mixture of hydroxamic acid 21 (0.02 mmoi) and toiuene (0.25 mL) at room temperature was added VO(0/-Pr)3 (0.01 mmol). The mixture was stirred at room temperature for 8hours. After that time, 88% cumene hydroperoxide (1.5 mmol) was added, followed by homoallyhc alcohol (l.Ommol). The reaction mixture was stirred for 24 hours and then quenched by the addition of trimethyiphos-phite (1.5 mmol). The mixture was extracted with ethyi acetate. The combined organic layers were dried over Na2S04, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gei to give the desired epoxide. 

Rossiter BE, Shaipless KB. Asymmetric epoxidation of homoallylic alcohols. Synthesis of (—)-7-amino-p-(i )-hydroxybutyric acid (GABOB). J. Org. Chem. 1984 49(20) 3707-3711. 

MakitaN, Hoshino Y, Yamamoto H. Asymmetric epoxidation of homoallylic alcohols and application in a concise total synthesis of (-)-a-bisabolol and (-)-8-ep -a-bisabolol. Angew. Chem. Int. Ed. 2003 42(8) 941-943. 

Okachi T, Murai N, Onaka M. Catal)Tic enantioselective epoxidation of homoallylic alcohols by chiral zirconium complexes. Org. Lett. 2003 5(l) 85-87. 

Reminiscent of the iodolactionization process, Bartlett and Jemstedt developed an indirect but efficient way for the diastereoselective epoxidation of homoallylic alcohols. They found that the treatment of the diethyl-phosphate ester of a homoallylic alcohol such as 10 with iodine produced cyclic phosphate 11 in high yield and good syw-diastereose-lectivity. After hydrolytic treatment with sodium ethoxide, the epoxide 12 was formed with no change of diasteromeric ratio (Scheme 37.3). 

---