Double bonds directed epoxidations

In the following epoxidation step, m /a-chlorobenzoic acid (w-CPBA) has the choice to attack the 10,11-double bond or the 13,14-double bond. Because a hydrogen bond between the alcohol at C-9 and the peracid stabilizes the transition state 80, only the 10,11-double bond is epoxidized. In addition, this hydrogen bond also directs the attack to come from the same side as the alcohol and thus leads to a high substrate-controlled stereoselectivity. 

When there is no C=0 present at Cn in the l,4-diene-3-one precursor, as in (134), the more nucleophilic 4,5-double bond is epoxidized with DMD affording (135) exclusively (Equation (9)) <94JOC4304>. The observed regioselectivities have been ascribed to the directing effect of the Cn-carbonyl favoring the approach of DMD from the a-face of the dienoic A-ring. 

In 1985, O Malley et al. published the total syntheses of rac-averufin (103) and rac-nidurufin (104) (65). These are both early precursors of the aflatoxins in their biosynthesis. Nidurufin (104) is the direct successor of averufin (103) and the direct precursor of versiconal hemiacetal acetate (12, see Scheme 2.1). Nidurufin (104) and averufin (103) are accessible by the same synthesis route only the two last steps differ firom each other (see Scheme 2.17). The first reaction was a double Diels-Alder reaction with dichloro-p-benzoquinone (97) and two equivalents of diene 98. Then, three of the four alcohol functions were selectively MOM-protected (—> 99). The remaining alcohol was converted into the allyl ether and then subjected to a reductive Claisen rearrangement, followed by MOM-protection of the redundant alcohol ( 100). By addition/elimination of PhSeCl, 101 was formed. Deprotonation of t-butyl 3-oxobutanoate, followed by reaction with 101 yielded the pivotal intermediate 102. This could be converted into rac-averufin (103) by deprotection of the alcohols and decarboxylation at the side chain. The last step was a p-TsOH-catalyzed cyclization to give 103. By treating 102 with /m-CPBA, the double bond is epoxidized. rac-Nidurufin (104) was then formed by cyclization of this epoxide under acidic conditions. 

When heated in the presence of a carboxyHc acid, cinnamyl alcohol is converted to the corresponding ester. Oxidation to cinnamaldehyde is readily accompHshed under Oppenauer conditions with furfural as a hydrogen acceptor in the presence of aluminum isopropoxide (44). Cinnamic acid is produced directly with strong oxidants such as chromic acid and nickel peroxide. The use of t-butyl hydroperoxide with vanadium pentoxide catalysis offers a selective method for epoxidation of the olefinic double bond of cinnamyl alcohol (45). 

Another unusual directive effect has been observed in the epoxidation of A -double bonds, which in most cases takes place predominantly on the a-side, e.g. 23. However, when carbon-17 is sp hybridized, epoxidation gives exclusively the -epoxide e.g., 25). 

Epoxidation of conjugated dienes can be regioselective when one double bond is more electron-rich than the other otherwise mixtures of mono- and diepoxides will be obtained. When the alkene contains an adjacent stereocenter, the epoxidation can be diastereoselective [2]. Hydroxy groups can function as directing groups, causing the epoxidation to take place syn to the alcohol [2, 3]. 

Note that it is necessary to open the epoxide (9) and substitute to get (10) - direct attack on a double bond would give the wrong isomer (11). Inversion of... 

Hydroxy groups exert a directive effect on epoxidation and favor approach from the side of the double bond closest to the hydroxy group.78 Hydrogen bonding between the hydroxy group and the reagent evidently stabilizes the TS. 

Another elegant use of nonadienoate is the synthesis of a pheromone called brevicomin (148) (132). The ester was converted to 1,6-nonadiene (149). The terminal double bond was selectively converted to glycol via epoxide. The oxidation with PdCI2 produced brevicomin directly by intramolecular oxidative acetal formation. 

Unsaturated epoxides are reduced preferentially at the double bonds by catalytic hydrogenation. The rate of hydrogenolysis of the epoxides is much lower than that of the addition of hydrogen across the carbon-carbon double bond. In a, -unsaturated epoxides borane attacks the conjugated double bond at -carbon in a cis direction with respect to the epoxide ring and gives allylic alcohols [660], Similar complex reduction of epoxides occurs in a-keto epoxides (p. 126). 

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