Subsequent Transformations of Epoxides

Epoxides are useful synthetic intermediates and the conversion of an alkene to an epoxide is often part of a more extensive overall transformation. Advantage is taken of the reactivity of the epoxide ring to introduce additional functionality. As epoxide ring opening is usually stereospecific, such reactions can be used to establish stereochemical relationships between adjacent substituents. Such two- or three-step operations can achieve specific oxidative transformations of an alkene that might not be easily accomplished in a single step. 

These fundamental aspects of epoxide ring opening were established by kinetic and isotopic labeling studies2 The dominant role of bond cleavage in acidic hydrolysis is indicated by the increase in rates with additional substitution. Note in particular that the 2,2-dimethyl derivative is much more reactive than the cis and trans disubstituted derivative, as expected for an intermediate with carbocation character. 

The opening of cis- and fran5 -2,3-dimethyloxirane in methanol or acetic acid is a stereospecific anti addition3  

In the case of epoxides of 1-arylcyclohexene, there is direct evidence for a carbocation intermediate. The hydrolysis product can be diverted by addition of azide ion as a competing nucleophile. As expected for a carbocation intermediate, both the cis and trans diols are formed. 

The conformationally biased cis- and trans-4-t- )vXy derivatives were examined. The stereochemistry of both acid- and base-catalyzed reactions was investigated in 85 15 DMSO-H2O. Under acidic conditions the epoxides give anti ring opening and the reaction is stereospecific. The base-catalyzed reactions involve tranx-diaxial ring opening. The acid-catalyzed reactions occur by preferential opening of the benzylic bond with inversion.  

SECTION 10.2. ADDITION OF OXYGEN AT CARBON-CARBON DOUBLE BONDS 

Epoxidation Followed by Ring Opening to an Allyl Alcohol 

Alumina has been found to be a useful catalyst for nucleophilic ring opening of epoxides by amines, alcohols, carboxylic acids, and thiols. These reactions are believed to be concerted processes in which both the alumina and nucleophile participate with the alumina acting as a Lewis acid. In unsymmetrical epoxides, the reactions show a modest (1 2-l 10) selectivity for attack by the nucleophile at the less hindered carbon of the epoxide. 

Double bonds having oxygen and halogen substituents are susceptible to epoxida-tion, and the reactive epoxides that are thereby generated serve as intermediates in some useful synthetic transformations. Vinyl chlorides furnish haloepoxides, which can rearrange to a-haloketones  

Oxidations an epoxide is often part of a more extensive molecular transformation.109 In many 

Epoxidation followed by ring opening to an allyl alcohol 

Addition of Oxygen at Carbon-Carbon Double Bonds 

When simple aliphatic epoxides such as propylene oxide react with hydrogen halides, the dominant product has the halide at the less-substituted primary carbon.111 

In cyclic systems, ring opening gives the diaxial diol. 

Epoxidation may be preliminary to solvolytic or nucleophilic ring opening in synthetic sequences. In acidic aqueous solution, epoxides are opened to give diols by an anti addition process. In cyclic systems, ring opening occurs to give the diaxial diol. 

Base-catalyzed reactions, in which the nucleophile provides the driving force for ring opening, usually involve breaking of the epoxide bond at the less substituted 

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When asymmetric epoxidation of a diene is not feasible, an indirect route based on asymmetric dihydroxylation can be employed. The alkene is converted into the corresponding syn-diol with high enantioselectivity, and the diol is subsequently transformed into the corresponding trans-epoxide in a high-yielding one-pot procedure (Scheme 9.5) [20]. No cpirricrizalion occurs, and the procedure has successfully been applied to natural product syntheses when direct epoxidation strategies have failed [21]. Alternative methods for conversion of vicinal diols into epoxides have also been reported [22, 23]. 

Synthesis of Allylic Alcohol Xa. A 3.84 g sample of olefin VII was treated with m-chloroperoxybenzoic acid (MCPBA) in dichloromethane for 1.5 hours at 0°C and 2.5 hours at 20°C. The NMR spectrum of the crude product indicated a mixture of approximately 75% epoxide VIII and 25% IX (structural assignments based upon assumed epoxidation preferentially from the less hindered side). Purification by column chromatography furnished 0.61 g of IX and 2.58 g of VIII. The separation was performed for characterization purposes the crude epoxidation mixture was suitable for subsequent transformations. 

Subsequent deprotection of the desired z-isomer (39a) afforded desoxye-pothilone B (epothilone D), which had previously been epoxidized to epothilone B (5) [14b]. Alcohol 37 did not undergo RCM using 1 or 3 [14b]. The failure of initiator (1) to effect this transformation may be due to its incompatibility with unprotected hydroxyl groups [19]. 

The wide scope application of this transformation arises not only from the utility of epoxide compounds but also from the subsequent regiocontrolled and stereocontrolled nucleophilic substitution (ring-opening) reactions of the derived epoxy alcohol. These, through further functionalization, allow access to an impressive array of target molecules in enantiomerically pure form. 

Scheme 4-21 shows the preparation of L-threitol and L-erythritol.38 Epoxy alcohols (2J ,3iS)-61 and (2S,3/ )-61. generated by asymmetric epoxidation, are exposed to sodium benzenethiolate and sodium hydroxide in a protonic solvent to undergo base-catalyzed rearrangement, yielding the threo-diol 62 and erythro-diol 63, which can then be converted to the corresponding tetraacetate of l-threitol 67 and L-erythritol 69 through subsequent transformations. 

Using the enolate of ferf-butyl bromoacetate with 1,5-lactones 58 (Scheme 18) led directly to exocyclic epoxides 59, which were subsequently transformed into compounds 60 [77]. Alternatively, cationic reduction of epoxides 59a-c provided C-glycosyl compounds 61a-c. Upon esterification of the latter as... 

Chemistry of low-valent titanium and zirconium has produced a number of powerful methods for the transformation of carbohydrates to carbocyclic compounds. The Ti(III)-mediated generation of a radical from epoxides and its subsequent cyclization [32] was discussed earlier under free radical methods (see Scheme 9). As shown in Scheme 12,... 

The above system could further be applied to the epoxidation of allylic alcohols [35, 36], monoterpenes [37] and oc,P-unsaturated carboxylic acids [38], the oxidation of alcohols [35, 36], amines [39] and alkynes [40], and the oxidative transformation of diols [35, 41-44]. The subsequent spedroscopic and kinetic studies by many researchers show that [P04 W0(02)2 4]3 is a true catalytically adive species formed by the readion of H3[PW12O40] with excess H202 (Figure 6.3) [45-48],... 

This concept has been applied for the synthesis of the structurally complex and highly oxyfunctionalized triquinane (—)-coriolin (Sch. 31) [61]. Two carbonyl groups, both in the right position for 1,2-acyl shift were present in the trimethyl-functionalized bicyclo[2.2.2]octenone 58. With a site-selectivity of 85% the expected regioisomeric tricyclic dione 59 was formed as a mixture of epimers (Sch. 31). Subsequent transformations involving the annulations of the third five-membered ring as well as epoxidation and hydroxylation steps led to the desired natural product... 

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