Epoxides synthesis from halohydrins

Although the bulk of this section is concerned with the formal addition of a single atom across both ends of a C=0 double bond, halohydrins also result from the addition of a nucleophile (H or R ) to carbonyl compounds bearing an adjacent leaving group or its equivalent (path b, Scheme 1). The use of this approach for epoxide synthesis was pioneered byComforth and coworkers as early as 1959. The scope of this process is very wide, so only a few highlights will be covered here. 

Epoxides can also be prepared from halohydrins, themselves produced by electrophilic addition of ffO X to alkenes (Section 8.3). When a halohydrin is treated with base, ffX is eliminated and an epoxide is produced by an intramolecular Williamson ether synthesis. That is, the nucleophilic alkoxide ion and the electrophilic alkyl halide are in the same molecule. 

Base promoted cyclization of vicinal halohydrms (Section 16 10) This reaction is an intramolecu lar version of the Williamson ether synthesis The alcohol function of a vicinal halohydrin is con verted to its conjugate base which then displa ces halide from the adjacent carbon to give an epoxide... 

Silica gel-based catalytic systems have been described as efficient promoters for a number of organic reactions.28 Illustrative examples include the oxidative cleavage of double bonds catalyzed by silica-supported KM11O4,29 reaction of epoxides with lithium halides to give /i-halohydrins performed on silica gel,30 selective deprotection of terf-butyldimethylsilyl ethers catalyzed by silica gel-supported phosphomolybdic acid (PMA),31 and synthesis of cyclic carbonates from epoxides and carbon dioxide over silica-supported quaternary ammonium salts.32... 

Nakamura T, Nagasawa T et al (1991) A new catalytic function of halohydrin hydrogen-halide-lyase, synthesis of P-hydroxynitriles from epoxides and cyanide. Biochem Biophys Res Commun 180 124—130... 

Fig. 40 Concept for the two-step synthesis of enantiomerically pure (S)-epoxides out of aliphatic 1-halogenated 2-ketones. The ketone was reduced by a recombinant whole-cell catalyst bearing alcohol dehydrogenase from Lactobacillus kefir (LKADH) and glucose dehydrogenase (GDH) for regeneration of NADPH. Base-induced cyclization of the enantiomerically pure (5)-(3-halohydrin intermediate gave the desired (S)-epoxides in high yield and enantiomeric purity (>99% ee)...

Synthesis of Epoxides from Chiral Chlorohydrins. Asymmetric halogenation of CSA-derived esters allows for the formation of enantiomerically pure halohydrins and terminal epoxides (eq 23). ... 

The conversion of halohydrins into epoxides by the action of base is simply an adaptation of the Williamson synthesis (Sec. 17.5) a cyclic compound is obtained because both alcohol and halide happen to be part of the same molecule. In the presence of hydroxide ion a small proportion of the alcohol exists as alkoxide this alkoxide displaces halide ion from another portion of the same molecule to yield the cyclic ether. 

Synthesis of Epoxides from Haiohydrins (Section 11.8C) Formation of the halohydrin and the following intramolecular Sf 2 reaction are both stereoselective (the configuration of the alkene is retained in the epoxide) and stereospecific (for alkenes that show ds, trans isomerism, the configuration of the epoxide depends on the configuration of the alkene). 

Oxirans. - The synthesis of l,2-anhydro-3,4-di-0-benzyl-6-deoxy-a-D-glucopyranose and its conformational analysis have been reported. A range of epoxides have been prepared by base treatment of bromohydrins, which were made by reaction of hydrogen bromide with aldonolactones. A one-pot conversion of vicinal diols into epoxides employs halohydrin ester intermediates generated from cyclic orthoacetates and either acetyl bromide or trimethylsilyl chloride. Levoglucosenone has been transformed into l,6 3,4-dianhydro-p-D-talopyranose by way of a trn/w-iodo-acetoxylation of the alkene moiety... 

Epoxides can be produced by elimination of HCl from vidnal-halohydrins by halohydrin dehalogenase enzymes. These enzymes can be used for the resolution of racemic halohydrins to chiral halohydrins that can be converted easily to chiral epoxides, an important building block for synthesis of variety of compounds (Figure 1.14). 

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