Base-catalyzed reactions, with epoxides

The base-catalyzed reaction of epoxide with phenol, in equimolar amounts, is somewhat slower than that of the alcohol-epoxide with the same catalyst. The mechanism of reaction is given in the following reactions ... 

Mechanism 14-4 Base-Catalyzed Opening of Epoxides 653 14-14 Orientation of Epoxide Ring Opening 654 14-15 Reactions of Epoxides with Grignard and Organolithium Reagents 656 14-16 Epoxy Resins The Advent of Modern Glues 656 Summary Reactions of Epoxides 658 EssentialTerms 660 Study Problems 662... 

The reaction of an epoxide with hydroxide ion leads to the same product as the acid-catalyzed opening of the epoxide a 1,2-diol (glycol), with anti stereochemistry. In fact, either the acid-catalyzed or base-catalyzed reaction may be used to open an epoxide, but the acid-catalyzed reaction takes place under milder conditions. Unless there is an acid-sensitive functional group present, the acid-catalyzed hydrolysis is preferred. 

When an unsymmetrical secondary alcohol is formed, depending on which carbon-oxygen bond is cleaved. With propylene oxide, for example, a base-catalyzed reaction favors the formation of the secondary alcohol almost exclusively, whereas, a non-catalytic or acid-catalyzed alcoholysis yields a mixture of the isomeric ethers. However, the reactions of other a-epoxides, such as 3,4-epoxy-l-butene, 3,4-epoxy-l-chloropropane (epichlorohydrin), 3,4-epoxy-l-propanol (glycidol), and styrene oxide, are more complicated with respect to which isomer is favored. ... 

Epoxides. The reaction between epoxides and hydroxyl groups is an acid- or base-catalyzed reaction however, all work in the wood field has been with base-catalyzed reactions ... 

Epoxides undergo acid-catalyzed reactions with extreme ease, and—unlike ordinary ethers—can even be cleaved by bases. Some of the important reactions are outlined below. 

Let us look, for example, at the reaction of ethylene oxide with phenol. Acid catalyzes reaction by converting the epoxide into the highly reactive protonated epoxide. Base catalyzes reaction by converting the phenol into the more strongly nucleophilic phenoxide ion. 

Before all these acetal-based protecting groups were introduced, the tetrahydropyranyl (THP) ether had found extensive use in organic synthesis. It can easily be synthesized from a variety of hydroxy-containing compounds like carbohydrates, amino acids, steroids and nucleotides by the acid-catalyzed reaction with dihydropyran. It is stable to bases, but the protection is removed through acidic hydrolysis with hydrochloric acid, toluenesulfonic acid or acidic ion-exchange resin (Scheme 27). In the case of acid sensitive substrates, e.g. containing an epoxide or a further acetal, pyridinium p-toluenesulfonate should be applied for particularly mild deprotection conditions. ... 

Reactions with unsaturated compounds. /-Butyl hydroperoxide decomposes smoothly at 95-105° and hydroxylates double bonds, and even a,)3-unsaturated ketones the reactions are catalyzed by small amounts of osmium tetroxide and afford cir-glycols. In benzene solution in the presence of Triton B as catalyst it converts a ,/3-unsaturated ketones into the corresponding epoxides in yields of 50-90%. The steric requirement of the base-catalyzed reaction are indicated by the failure to react with isophorone or A -3-ketosteroids. Payne effected smooth preparation of /3-phenylglycidaldehyde by allowing cinnamaldehyde and /-butyl... 

The base-catalyzed reaction, however, proceeded readily at 100 C with 0.2% mol of potassium hydroxide and exhibited a high degree of selectivity. As can be seen from Figure 6, disappearance of phenol and epoxide proceeded at the same rate throughout the course of the reaction. This phenomenon indicates that epoxide reacted with phenol to the essential exclusion of any epoxide-alcohol reaction, Shechter and Wynstra (8) proposed a mechanism in which the phenol first is ionized to phenoxide ion as shown in Reaction 24 ... 

In a variation on this theme MgioAl2(OH)24C03 has been shown to catalyze the oxidation of a variety of olefins-linear and cyclic-and unsaturated alcohols and ketones with H2O2 in the presence of benzonitrile [60]. The reaction involves in situ formation of the Payne reagent [61], PhC(OOH)=NH, by base-catalyzed reaction of H2O2 with benzonitrile (Eq. 5). Reaction with the olefin then affords the epoxide and one equivalent of benzamide (Eq. 6). 

Epoxides from ],2-diols. A onc-pol conversion of 1,2-diols into epoxides involves conversion to an orthoestcr 1 by acid-catalyzed reaction with trimethyl orthoacetatc. This derivative is then treated with acetyl chloride, bromide, or iodide and (C l,).,SiCI with inversion at the halide center formed. Base-catalyzed hydrolysis and cyclization provides the epoxide with a second inversion. 

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. ... 

The enantiomeric fragment ( S)-392 is available from 386 by mesylation (393) followed by base-catalyzed cyclization (with inversion of configuration) to the (R)-epoxide 388. A similar series of reactions transforms (i )-388 to the iodide (S)-392 with 100% ee. 

The basic catalysis of the epoxide-phenol reaction has been studied by a variety of authors (12,13). In general, the conclusion has been that basic catalysis gives selectivity for the phenol-epoxide reaction over the secondary alcohol-epoxide reaction (the secondary alcohol being formed from the opening of an epoxide). Although the base catalyzed reaction has been studied, the specific mechanism for triphenylphosphine Catalysis has not been determined. We propose the mechanism shown in Reaction Scheme 3 which is consistent with our experimental results. 

There is a frequently noted incompatibility of organoiithiums with many chiral Lewis acids, which are often employed for asymmetric openings of epoxides [99]. Analogous Lewis base-catalyzed reactions are rare [100]. However, activation by Lewis acids, such as BFj OEt2, is necessary for the opening of less reactive epoxides [101]. While organoiithiums are rarely employed, applications of hetero-nucleophiles are well known in enantioselective desymmetrizations of meso-epoxides [102]. 

Although acid-catalyzed and uncatalyzed alcohol-epoxide reactions are known to lead to a mixture of isomeric species, the base-catalyzed reactions give a product that is almost exclusively a primary ether and a secondary alcohol. If, then, a secondary alcohol is reacted with a glycidyl ether under conditions of base catalysis (to yield a new secondary alcohol), the almost exclusive reaction will be that of glycidyl ether with secondary alcohol. The reaction would still be complicated by the competition of the new hydroxyls with the starting alcohol for epoxide. 

Thus in the aldol addition, just as in the case of epoxide-opening reactions, the chloride ion, formed as a necessary consequence of the mechanism of Lewis base catalysis with chlorosilanes, is not innocuous. In fact, it is a competent nucleophile that can attack an aldehyde or an epoxide activated by the Lewis base-coordinated silicenium cation in an intermolecular fashion. The desire to understand these two seemingly inconsistent results obtained in our study of the Lewis base-catalyzed reactions of trichlorosilanes presented an opportunity for the development of novel catalytic processes. For example, if a chloride ion can capture these activated electrophiles, could other exogenous nucleophiles be employed to intercept these reactive intermediates If so, a wide variety of bond-forming processes mediated by the phosphoramide-bound chiral Lewis acid [LB SiCls]" would be feasible. At this point it remained unclear if (1) an exogenous nucleophile could compete with the ion-paired chloride and (2) what kinds of nucleophiles could be compatible with the reaction conditions. 

Such copolymers of oxygen have been prepared from styrene, a-methylstyrene, indene, ketenes, butadiene, isoprene, l,l-diphen5iethylene, methyl methacrjiate, methyl acrylate, acrylonitrile, and vinyl chloride (44,66,109). 1,3-Dienes, such as butadiene, yield randomly distributed 1,2- and 1,4-copolymers. Oxygen pressure and olefin stmcture are important factors in these reactions for example, other products, eg, carbonyl compounds, epoxides, etc, can form at low oxygen pressures. Polymers possessing dialkyl peroxide moieties in the polymer backbone have also been prepared by base-catalyzed condensations of di(hydroxy-/ f2 -alkyl) peroxides with dibasic acid chlorides or bis(chloroformates) (110). 

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