Epoxides, preparation from alkenes

The following section describes the preparation of epoxides by the base promoted ring closure of vicinal halohydrms Because vicinal halohydrms are customarily prepared from alkenes (Section 6 17) both methods—epoxidation using peroxy acids and ring closure of halohydrms—are based on alkenes as the starting materials for preparing epoxides... 

Since the epoxidation of alkenes with peracids was discovered by Prilezajew in 1909 [29], epoxides have played a major role in organic chemistry and industry, providing important intermediates for the synthesis of more complex molecules. Metal-catalyzed epoxidation reactions have received much attention in recent decades since the discovery of the Sharpless epoxidation [30, 31], but most epoxides were prepared from alkenes primarily by their interaction with peracids. 

The NMR spectroscopy of oxiranes has attracted considerable interest because the oxiranes can be easily prepared from alkenes under mild conditions. Thus, it is worthwhile investigating so-called epoxidation-induced shifts (E1S) by comparing the observed 13C chemical shifts of an oxirane to the shifts in the corresponding alkene440 441. However, a differentiation of diastereomers using these shifts is not always reliable. The situation is more favorable in confor-... 

Epoxides (oxiranes) are three-membered cyclic ethers. The simplest and commercially most important example is ethylene oxide, manufactured from ethylene, air, and a silver catalyst. In the laboratory, epoxides are most commonly prepared from alkenes and organic peroxy acids. 

Epoxides can be synthesised by the action of aldehydes or ketones with sulphur-ylides. They can also be prepared from alkenes by reaction with m-chloroperoxybenzoic acid. 

Epoxides may be prepared from alkenes by the action of a peroxy acid such as m-chloroperbenzoic acid (Scheme 2.20a) or via the formation of a bromohydrin or iodohydrin and the treatment of this with base (Scheme 2.20b). Since the initial electrophile, the bromine or the iodine, is displaced in the second step when the epoxide is formed, the stereochemistry of this epoxidation is likely to differ from that of the reaction with peroxy acid. 

Carbon-Oxygen Bond Formation. CAN is an efficient reagent for the conversion of epoxides into /3-nitrato alcohols. 1,2-cA-Diols can be prepared from alkenes by reaction with CAN/I2 followed by hydrolysis with KOH. Of particular interest is the high-yield synthesis of various a-hydroxy ketones and a-amino ketones from oxiranes and aziridines, respectively. The reactions are operated under mild conditions with the use of NBS and a catalytic amount of CAN as the reagents (eq 25). In another case, N-(silylmethyl)amides can be converted to A-(methoxymethyl)amides by CAN in methanol (eq 26). This chemistry has found application in the removal of electroauxiliaries from peptide substrates. Other CAN-mediated C-0 bondforming reactions include the oxidative rearrangement of aryl cyclobutanes and oxetanes, the conversion of allylic and tertiary benzylic alcohols into their corresponding ethers, and the alkoxylation of cephem sulfoxides at the position a to the ester moiety. 

However, we know of no reactions that convert alcohols directly to epoxides. Because we do know that epoxides are prepared from alkenes, we expand our retrosynthesis to reflect that. 

Chlorohydrin B, prepared from alkene A by addition of Cl and OH, is converted to epoxide C with base. C is converted to estrone in one step. 

The preparation of lyn-epoxide (19) from alkene (18) by Sharpless epoxidation proceeds with inversion of the selectivity expected by the empirical rule established for simple allylic alcohols. ... 

Oxaziridines unsubstituted at nitrogen as well as some iV-acylated oxaziridines offer synthetic potentialities due to their ability to transfer their nitrogen function to nucleophiles (Section 5.08.3.1.4). The simplicity of preparation of some aziridines from alkenes and the Spiro oxaziridine (S2) equals the simplicity of epoxidation. Aziridine (299), for example, is obtained by simple heating of indene with (52) in toluene (74KGS1629). 

Is either of the epoxides formed in the preceding reactions chiral Is either epoxide optically active when prepared from the alkene by this method ... 

A mixed-valent polymolybdate on active carbon was prepared from molybdenum metal and H202, followed by the addition of active carbon to the aqueous solution [114,115], This catalyzed the epoxidation of several alkenes in 2-propanol using H202 as an oxidant, while the efficiency of H202 utilization was very low (< 25%). The epoxidation likely proceeded mainly on the surface of the catalyst because the recovered catalyst showed almost similar catalytic activity. 

An epoxide is formed from alkene and peroxymethanoic acid (H202 -l- HC02H) but is cleaved by the HC02H present to a frans-diol. Alternatively, osmium tetroxide may be used in fe/t-butyl alcohol and leads to the c/ s-diol. Potassium permanganate in neutral can be useful for preparation of c/ s-glycols. (See Section 11-70.)... 

Sharpless epoxidation of (E)-(l,2-dialkyl)vinylsilanols 13, prepared from hydrolysis of ( )-( 1,2-dialkyl )vinyldimethylbutoxysilanes 12, gave silylepoxides 14, which were treated with Et4NF in MeCN to afford epoxides 15 in 62-70% overall yield and 44-70% ee (Scheme 6AA.6).7 The overall transformation can be considered as asymmetric epoxidation of simple internal alkenes. This approach was applied to the synthesis of a naturally occurring insect sex pheromone (+)-disparlure.7... 

Homologous biphenyl and binaphthyl tertiary azepines (4) and quaternary iminium salts, prepared from (+)-(5,5 )-L-acetonamine, behave as effective catalysts for the enantioselective epoxidation of unfunctionalized alkenes with Oxone (ee up to 83%).113... 

Using retrosynthetic analysis, we recognize that the c/.v-epoxide can be prepared from the c/s-alkene. The m-alkene can be prepared by catalytic hydrogenation of an alkyne. Finally, substituted alkynes can be prepared by nucleophilic substitution reactions using acetylide ion nucleophiles (see Section 10.8). On the basis of this analysis, the synthesis reported in the literature was accomplished as shown in Figure 23.3. 

The epoxide can be prepared from an alkene and the amide from a carboxylic acid. The new target. 2-ethyl-2-hexenoic acid, has a CC double bond in conjugation with the carbonyl group of the carboxylic acid. Whenever a compound with an ,/3-unsaturated carbonyl group is encountered, it is worthwhile to consider the possibility of using an aldol condensation (see Section 20.5) or a related reaction to prepare it. To examine this possibility, the aldehyde that will provide the carboxylic acid upon oxidation is disconnected at the double bond. Because both fragments produced by this disconnection are the same, it is apparent that an aldol condensation of butanal can be employed to prepare this compound. The synthesis was accomplished as shown in Figure 23.5. 

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