Hydroxy esters from epoxides

Some efficient syntheses have been reported such as those of p-hydroxy esters from tris(methylthio)methyllithium and epoxides. The case of a malate derivative from a commercially available chiral epoxide is described [286]. 

A suspension of thallium (III) nitrate in hexane reacts with epoxides to give the corresponding -hydroxy nitrate esters in good yield. The same reagent in acetonitrile has been used to synthesize a-nitratoketones from substituted acetophenones, 1,2-dinitrate esters from alkenes, and 1,3-dinitrates from ring-opening nitration of cyclopropanes. ... 

Carbonylation of epoxides.4 The epoxide of a 1-alkene undergoes carbony-lation under catalysis with Co2(CO)8 in the presence of K2C03 (1 equiv.) in ethanol at moderate temperatures to afford (3-hydroxy esters. A by-product is the ketone formed by rearrangement of the epoxide. This reaction provides an essential step in the synthesis of the cyclopentenone 3 from the epoxide (1) of ethyl 10-unde-cenoate. 

Diols react with 1,2-dihalo compounds under basic conditions to form 1,3-dioxolanes. Treatment of 2-chloroethyl hemiacetals with base is an alternative approach to these cyclic acetals, " Similarly, 2-chlorocthyl ester enolatcs cyclizc readily.2-Hydroxy- " 2-phenoxy-, " and 2-alkoxy-l,3-dioxolanes are synthesized from epoxides "" or.vr/ -tet-raphenylethylene dichloride " using trifluoroacetic acid. " its silver salt, " or alkyl trifluoro-acetates. ... 

Addition of lithium enolates derived from esters and ketones to epoxides has been the object of some consideration, because it offers a direct route for the synthesis of y -hydroxy esters and y-hydroxy ketones, very useful for difunctionahzed organic compounds" . In fact, more complex molecules can be synthesized by using these compounds as synthons... 

Indeed, in a patent held by the Dow Chemical Company(1)it is observed that epichlorohydrin (or other suitable 1,2-epoxide) is required in order to obtain high yields of glycidyl esters from 2-hydroxy-3-chlorophenyl esters. A mechanism involving transepoxidation was proposed (Fig. 17). 

Our third synthesis of the enantiomers of ipsdienol started from the enantiomers of serine as shown in Figure 4.66.116 (A-Serine was converted to epoxide A, which was treated with a Grignard reagent prepared from chloroprene to give hydroxy ester B. Subsequently, B afforded (7 )-ipsdienol (112, >96% ee). Similarly, (R)-serine furnished (S)-112. 

The y9-titanoxy radicals formed after epoxide opening can also add to a.,P-unsaturated esters. The resulting enol radicals are reduced by a second equivalent of the titanocene reagent to yield titanium enolates. After aqueous workup the corresponding hydroxy esters or lactones are obtained. This method allows easy access to (5-lactones in a one-step procedure from epoxides (Scheme 21) [33bj. 

The availability of chiral epoxides (168), for example from yeast reductions, would extend the method to the production of chiral hydroxy-esters. 

One of the most potent frameworks for the synthesis of two contiguous stereochemically defined asymmetric centers is the chiral epoxy functionality. Prepared in molar-scale quantity from dimethyl L-tartrate (la), bromohydrin 860 is a shelf-storable solid that undergoes selective reduction at the a-hydroxy ester function with borane-dimethylsulfide complex in the presence of catalytic sodium borohydride to provide a 4 1 mixture of methyl (2S,3S)-2-bromo-3,4-dihydroxybutanoate (861) and methyl (2i, 3i )-3-bromo-2,4-dihydroxybutanoate (862). Without purification this mixture is treated with ert-butyldimethylsilylchloride and then exposed to sodium methoxide, which results in conversion to the single epoxide methyl (2i, 3iS)-4-( err-butyldimethylsilyloxy)-2,3-epoxybutanoate (863) in 95% yield and with 99% optical purity (Scheme 188). 

Further proof of the intermediacy of the iodohydrins 85 in the formation of the hydroxy-tetrahydrofurans 80 came from two sources. Firstly, treatment with potassium carbonate led to formation of the corresponding epoxides. Secondly, by providing a second alkene function, suitably positioned to trap the iodohydrin hydroxyl by a 6-eto-trig iodocyclization, we have been able to intercept these species and hence define a new approach to substituted pyrans. Thus, treatment of the dienyl hydroxy-ester 90 with iodine and NaHCO, resulted in the formation of pyrans 92 in the ratio of 3.2 1. Presumably, initial iodohydrin formation 91 is followed by a relatively non-stereoselective 6-exo cyclization. Further chemistry of such products has yet to be carried out, especially efforts to distinguish the two iodine atoms and to cyclize to give furopyran systems <01M1001>. 

---