Epoxide ring opening, acetic acid

Very successful has been the aldolase-catalyzed aldol reaction as exemplified inO Scheme 14 [97]. The required (R)-3-thioglyceraldehyde (20) is obtained from regioselective epoxide ring opening of (5)-glycidaldehyde diethyl acetal with thioacetic acid and its potassium salt. Con-... 

Exo- and endo-cyclic ring closure reactions using 0-nucleophiles transform oxocarbenium ions into cyclic acetals. As an example of an endocyclic cyclization, epoxide ring opening of (96) with lithium dimethyl cuprate, and subsequent treatment of the resulting alcohol with acid, smoothly gives the bicyclic acetal (97), ° a key intermediate in the total synthesis of tirandamycic acid (Scheme 47). ... 

A similar transformation can be carried out under milder conditions by taking advantage of silyl ketene acetals, a masked form of the earboxylate dianion. When epichlorohydrin 53 was treated with the ketene acetal 79 in the presence of titanium(IV) chloride, a regioseleetive epoxide ring opening occurs at the less substituted carbon. Treatment of the crude reaction mixture with catalytic p-toluenesulfonic acid promoted a lactonization to the y-butanolide 80 in high overall yield <04T8957>. 

Another chemical route is based on the work of Kakinuma et al. (38), who synthesized the two chiral, deuterated epoxides shown in Scheme S. Separation of the two diastereomers and reductive epoxide ring opening with tritiated LiAlH4 followed by permanganate/periodate oxidation gave acetic acid which within the limits of detection was chirally pure (100 7% e.e.) (39). 

The effect of the reaction medium on the selectivity of epoxidation is best characterized by the ratio of the epoxidation rate and the epoxy ring opening. It has been found [17] that a decrease in water content in PAA increases the selectivity of epoxidation. Water and acetic acid which are contained in PAA can react with the formed epoxy ring as shown below (Schemes 20 and 21). 

Epoxi ester 1 effeetively rearranges to a 1 1 mixture of acetates 2 and 3 under acidic conditions (0.5 M H2SO4 in THF/H2O 9/1). It is believed that the reaction occurs through the formation of an orthoester intermediate 4 tiiat is subsequently hydrolyzed in the acidic medium (Scheme 25.1). This route provides a convenient method for the synthesis of polyhydroxylated compounds with control of the stereochemistry during the epoxide ring-opening step. 

A decisive solvent effect is also observed with other a,/ -epoxy ketones. Specifically, 3jS-hydroxy-16a,17a-epoxypregn-5-en-20-one and its acetate do not react with thiocyanic acid in ether or chloroform. However, the corresponding thiocyanatohydrins are formed by heating an acetic acid solution of the epoxide and potassium thiocyanate. As expected, the ring opening reaction is subject to steric hindrance. For example, 3j6-acetoxy-14f ,15f5-epoxy-5) -card-20(22)-enoIide is inert to thiocyanic acid in chloroform, whereas the 14a,15a-epoxide reacts readily under these conditions.Reactions of 14a,15a-epoxides in the cardenolide series yields isothiocyanatohydrins, e.g., (135), in addition to the normal thiocyanatohydrin, e.g., (134). 

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