Hydroxyl group-directed epoxidation

The hydroxyl group-directed epoxidation was utilized by M. Isobe et al. in their total synthesis of 11-deoxytetrodotoxin. ° The six-membered cyclic allylic alcohol was treated with mCPBA in the presence of a phosphate buffer to afford an almost quantitative yield of the desired (3-epoxide. 

On the other hand, H.B. Henbest realised that adjacent polar functional groups have a directing effect on the epoxidation of alkenes as well as on other related reactions [2]. A very well known example is the 5yn-directing effect of an ally lie hydroxyl group in epoxidations of cyclic alkenes (Scheme 10.1) ... 

In the epoxidation of acyclic allylic alcohols (Scheme 6), the diastereoselectivity depends significantly on the substitution pattern of the substrate. The control of the threo selectivity is subject to the hydroxyl-group directivity, in which conformational preference on account of the steric interactions and the hydrogen bonding between the dioxirane oxygen atoms and the hydroxy functionality of the allylic substrate steer the favored 7r-facial... 

Cl 1-25 of the milbemycins. The intramolecular spiroketalization theme was slightly altered to feature an endocyclic enol ether [86] by condensation of a lithio-2-benzenesulfonyl-tetrahydropyran with a suitable epoxide. An alternative but not enantiospecific approach from lactone B 3 comes from a double Baeyer-Villiger oxidation of bicyclo[2.2.1]heptane-2,5-dione to control [107] the relative stereochemistry in the B ring. The acetylenic partner was in turn derived from two different routes, the more selective being an anti hydroxyl group directed alkylation of a homopropargylic alcohol. 

Sharpless advanced this notion through using a metal-based epoxidation catalyst (Scheme 4.18) [44]. This approach took advantage of the capacity of VO(acac)j to coordinate simultaneously to alcohols and peroxides and promote regioselective epoxidations of allylic and homoal-lylic alcohols with iBuOOH as the oxidant, as shown by the conversion of 87 to 88. This approach also provides stereoselectivity, as shown by the transformation of 89 to 90 in which the hydroxyl group directs a yn-oxidation of the alkene. This procedure is selective because alkyl peroxides generally do not epoxidize alkenes but can be activated by coordination to the alcohol-coordinated vanadium Lewis acid. 

When the OAc group was a hydroxyl, the epoxidation selectivity was not very good, presumably because of the known directing effect of hydroxyl groups in peracid epoxidations. 

Our discovery that epoxides can initiate carbocationic polymerization led to the effective direct functionalization of PIBs with hydroxyl groups. Figure 7.18 shows our novel method of direct surface functionalization of SDIBSs using 4-(l,2-oxirane-isopropyl)-styrene, a new inimer. 

The anti stereospecificity of epoxidation by the peracid is interpreted as due to association of the reagent with the allylic hydroxyl group which directs the entering oxygen atom to the same face of the molecule. The stereospecificity of bromohydrin formation is explicable in terms of steric approach control involving initial attack of the bulky bromine atom on the face opposite to the benzylic hydroxyl group (7). 

The oxidative cyclization of vinylallenes need not be directed by a pendant hydroxyl group in order to succeed. The higher reactivity of the allene compared with the exocyclic methylene group in 73 (Eq. 13.23) with monoperphthalic acid leads primarily to the allene oxide which rearranges to cydopentenone 74 [27]. Inevitably some epoxidation of the alkene also takes place during the reaction. When m-CPBA is used as the oxidant, another side reaction is associated with m-chlorobenzoic add-mediated decomposition of the intermediate epoxide. It is possible to overcome this problem by performing the epoxidation in dichloromethane in a two-phase system with aqueous bicarbonate so as to buffer the add [28]. 

Allylic alcohols are interesting substrates for epoxidation because they produce epoxides with a hydroxyl group as additional functional group that is able to play an important role in the subsequent synthesis of complex molecules [105]. This synthesis aspect certainly benefits from the hydroxy-group directed selectivity of oxygen delivery. 

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