Reduction of epoxide

Regioselectivity of C—C double bond formation can also be achieved in the reductiv or oxidative elimination of two functional groups from adjacent carbon atoms. Well estab llshed methods in synthesis include the reductive cleavage of cyclic thionocarbonates derivec from glycols (E.J. Corey, 1968 C W. Hartmann, 1972), the reduction of epoxides with Zn/Nal or of dihalides with metals, organometallic compounds, or Nal/acetone (seep.lS6f), and the oxidative decarboxylation of 1,2-dicarboxylic acids (C.A. Grob, 1958 S. Masamune, 1966 R.A. Sheldon, 1972) or their r-butyl peresters (E.N. Cain, 1969). 

Perfluorinated epoxides, which are generally susceptible to C-O cleavage during nucleophihc attack, are cleaved by lithium alummum hydnde Of the available examples, reduction of epoxides from two types of internal olefm to give alcohols IS shown [4S] (equations 37a and 37b)... 

Reduction of epoxide 21 with lithium aluminium hydride gave a crystalline branched-chain methyl heptoside derivative 24. The NMR spectra of compounds 21 and 24 were very similar. In the spectrum of compound 24 the disappearance of the two sharp doublets at r 6.80 and 7.45 (2 protons) and the appearance of a singlet at r 8.65 (3 protons) is consistent with the reductive cleavage of epoxide 21 to give a substance 24 with a methyl substituent. The multiplet at r 7.40-8.50 ( 5 protons ) was assigned to the four protons of the two methylene groups and the hydroxylic proton. 

Hydride Transfer In some reactions, a hydride ion is transferred to or from the substrate. The reduction of epoxides with LiAlH4 is an example (10-85). Another is the Cannizzaro reaction (19-60). Reactions in which a carbocation abstracts a hydride ion belong in this category ... 

By studying the NMR spectra of the products, Jensen and co-workers were able to establish that the alkylation of (the presumed) [Co (DMG)2py] in methanol by cyclohexene oxide and by various substituted cyclohexyl bromides and tosylates occurred primarily with inversion of configuration at carbon i.e., by an 8 2 mechanism. A small amount of a second isomer, which must have been formed by another minor pathway, was observed in one case (95). Both the alkylation of [Co (DMG)2py] by asymmetric epoxides 129, 142) and the reduction of epoxides to alcohols by cobalt cyanide complexes 105, 103) show preferential formation of one isomer. In addition, the ratio of ketone to alcohol obtained in the reaction of epoxides with [Co(CN)5H] increases with pH and this has been ascribed to differing reactions with the hydride (reduction to alcohol) and Co(I) (isomerization to ketone) 103) (see also Section VII,C). 

Lithium triethylborohydride is a superior reagent for the reduction of epoxides that are relatively unreactive or prone to rearrangement.169... 

Before turning to epoxide opening with low valent metal complexes, the reduction of epoxides under Birch conditions [10-13] will be discussed very briefly for historical reasons. The initially formed radical is reduced further to give carbanionic species, that do not display the reactivity of radicals. No C - C bond-forming reactions have initially been reported. 

The reduction of epoxides occurs with the reagent combinations Et3SiH/BF3566 and EtjSiH/BI 3 01 T24<)7 The reductive iodination of epoxides is carried out with the combination of TMDO and iodine (Eq. 344).357 The yields are good to excellent. The reductive bromination of epoxides is accomplished in a similar manner. Trimethylchlorosilane is found to enhance these reactions.567... 

In contrast to Red-Al reductions, DIBAL-H or LiBH4/Ti(OPr1)4 reduction of epoxides yields 1,2-diols as the major products.32 When treated with DI-BAL-H, ratios of 1,3- to 1,2-diol ranging from 1 6 to 1 13 have been observed. 

Scheme 4.44 Total synthesis of mimulaxanthin via ring-opening reduction of epoxide 169.

Because the reduction potential of ether is usually more negative than that of halides, examples that belong to this category are rather rare. Generally, cathodic reduction of ethers is similar to that of alcohols, and nonactivated ethers are not reducible under the conditions of electroreduction. Activated ethers such as benzylic and allylic ethers are elec-trochemically reduced to a limited extent (Scheme 7) [1, 15, 16]. Reduction of epoxides is usually difficult however, electroreductive cleavage of activated epoxides to the corresponding alcohols is reported [17, 18]. The cleavage of the C—O bond of ethers is more easily accomplished in anodic oxidation than in cathodic reduction, which is stated in Chapter 6. 

More frequent than the deoxygenation of epoxides to alkenes is reduction of epoxides to alcohols. Its regiospecificity and stereospecificity depend on the reducing agents. 

Reagents of choice for reduction of epoxides to alcohols are hydrides and complex hydrides. A general rule of regioselectivity is that the nucleophilic complex hydrides such as lithium aluminum hydride approach the oxide from the less hindered side [511, 653], thus giving more substituted alcohols. In contrast, hydrides of electrophilic nature such as alanes (prepared in situ from lithium aluminum hydride and aluminum halides) [653, 654, 655] or boranes, especially in the presence of boron trifluoride, open the ring in the opposite direction and give predominantly less substituted alcohols [656, 657,658]. As far as stereoselectivity is concerned, lithium aluminum hydride yields trans products [511] whereas electrophilic hydrides predominantly cis products... 

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). 

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... 

Reduction of acetals or ortho esters 0-80 Reduction of epoxides 0-92 Cleavage of acetals or ortho esters with Grignard reagents... 

Pentanol was first used m conjunction with eodium reduction of epoxides in 1306 by Klinger and Lonnes,94 who converted tetruplu-ml ethylene oxide into tetraphenylethane (Eq. 323). The known facility... 

General aspects of the lithium aluminum hydride reduction of epoxides have been discussed briefly by EIiel4W> and also by Parker and Isaacs1801 within a broader context of nucleophilic reactions. Excellent reviews covering the literature up to 1966 are those of Brown, Gaylord,8 8 and also Micovic and Mihailovio.1188 No attempt to encompass fully the voluminous literature of this topio will be made in the present article, although a representative sampling has been collected in Table 9, to which reference may be made for further detail,... 

Deep-seated rearrangements have likewise been known to occur during lithium aluminum hydride reduction of epoxides. Among thw is the interesting reaction reported by Barton and Brooke i involving the morolic acid derivative shown in Eq. (402). 

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