Epoxides directed epoxidation

The epoxides may be converted into 1 2-glycols by hydrolysis. In some cases the 1 2-glycol may be produced directly by carrying out the epoxidation in the presence of water. If the 1 2-glycol is desired, it is usually better to employ performic acid or peracetic acid, the latter best in the presence of a trace of sulphuric acid. An epoxide is first formed, followed by the hydroxy-formate or hydroxy-acetate, and ultimately the 1 2-glycol ... 

Henbest Epoxidation- epoxidation directed by a polar group... 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

The direct oxidation of fluoroalkenes is also an excellent general synthesis procedure for the preparation of perfluoroepoxides (eq. 8). This method exploits the low reactivity of the epoxide products to both organic and inorganic free radicals. 

The optical activity of malic acid changes with dilution (8). The naturally occurring, levorotatory acid shows a most peculiar behavior in this respect a 34% solution at 20°C is optically inactive. Dilution results in increasing levo rotation, whereas more concentrated solutions show dextro rotation. The effects of dilution are explained by the postulation that an additional form, the epoxide (3), occurs in solution and that the direction of rotation of the normal (open-chain) and epoxide forms is reversed (8). Synthetic (racemic) R,.9-ma1ic acid can be resolved into the two enantiomers by crystallisation of its cinchonine salts. 

Additioaal uses for higher olefias iaclude the productioa of epoxides for subsequeat coaversioa iato surface-active ageats, alkylatioa of benzene to produce drag-flow reducers, alkylation of phenol to produce antioxidants, oligomeriza tion to produce synthetic waxes (qv), and the production of linear mercaptans for use in agricultural chemicals and polymer stabilizers. Aluminum alkyls can be produced from a-olefias either by direct hydroalumination or by transalkylation. In addition, a number of heavy olefin streams and olefin or paraffin streams have been sulfated or sulfonated and used in the leather (qv) iadustry. 

General Reaction Chemistry of Sulfonic Acids. Sulfonic acids may be used to produce sulfonic acid esters, which are derived from epoxides, olefins, alkynes, aHenes, and ketenes, as shown in Figure 1 (10). Sulfonic acids may be converted to sulfonamides via reaction with an amine in the presence of phosphoms oxychloride [10025-87-3] POCl (H)- Because sulfonic acids are generally not converted directiy to sulfonamides, the reaction most likely involves a sulfonyl chloride intermediate. Phosphoms pentachlotide [10026-13-8] and phosphoms pentabromide [7789-69-7] can be used to convert sulfonic acids to the corresponding sulfonyl haUdes (12,13). The conversion may also be accompHshed by continuous electrolysis of thiols or disulfides in the presence of aqueous HCl [7647-01-0] (14) or by direct sulfonation with chlorosulfuric acid. Sulfonyl fluorides are typically prepared by direct sulfonation with fluorosulfutic acid [7789-21-17, or by reaction of the sulfonic acid or sulfonate with fluorosulfutic acid. Halogenation of sulfonic acids, which avoids production of a sulfonyl haUde, can be achieved under oxidative halogenation conditions (15). 

Besides direct hydrolysis, heterometaHic oxoalkoxides may be produced by ester elimination from a mixture of a metal alkoxide and the acetate of another metal. In addition to their use in the preparation of ceramic materials, bimetallic oxoalkoxides having the general formula (RO) MOM OM(OR) where M is Ti or Al, is a bivalent metal (such as Mn, Co, Ni, and Zn), is 3 or 4, and R is Pr or Bu, are being evaluated as catalysts for polymerization of heterocychc monomers, such as lactones, oxiranes, and epoxides. An excellent review of metal oxoalkoxides has been pubUshed (571). 

Chlorohydrins from Epoxides. Traditionally epoxides have been manufactured by the dehydrochlotination of chlorohydrins. However, the reverse reaction may be used as a source of chlorohydrins, especially ia the case of ethyleae chlorohydria from ethyleae oxide [75-21-8] which is aow produced by the direct oxidatioa of the olefia. A study of the reactioa of hydrogea chloride with propyleae oxide [75-56-9] showed that an anhydrous system at low temperatures (<0° C) gives the highest yield of chlorohydria with best isomeric selectivity (16). 

For many years ethylene chlorohydrin was manufactured on a large iadustrial scale as a precursor to ethylene oxide, but this process has been almost completely displaced by the direct oxidation of ethylene to ethylene oxide over silver catalysts. However, siace other commercially important epoxides such as propylene oxide and epichlorohydrin cannot be made by direct oxidation of the parent olefin, chlorohydrin iatermediates are stiU important ia the manufacture of these products. 

When heated in the presence of a carboxyHc acid, cinnamyl alcohol is converted to the corresponding ester. Oxidation to cinnamaldehyde is readily accompHshed under Oppenauer conditions with furfural as a hydrogen acceptor in the presence of aluminum isopropoxide (44). Cinnamic acid is produced directly with strong oxidants such as chromic acid and nickel peroxide. The use of t-butyl hydroperoxide with vanadium pentoxide catalysis offers a selective method for epoxidation of the olefinic double bond of cinnamyl alcohol (45). 

A commonly used alternative to the direct bromination of ketones is the halogenation of enol acetates. This can be carried out under basic conditions if necessary. Sodium acetate, pyridine or an epoxide is usually added to buffer the reaction mixture. The direction of enolization is again dependent upon considerations of thermodynamic and kinetic control therefore, the proportion of enol acetates formed can vary markedly with the reaction conditions. Furthermore, halogenation via enol acetates does not necessarily give the same products as direct halogenation of ketones 3. 23... 

The influence of the conformational factors, which play a decisive role in directing oxide fission in the above cases is no longer operative in the case of 3-keto-5a,6a-epoxides and their 3-ethylene ketals. With these substrates the —I effect of the BFs-complexed 3-keto or 3-ketal grouping predominates leading to the fluorohydrins. Thus, treatment of both 5a,6a-oxidopregnane-3,20-dione (35) and its 3,20-bisethylene ketal with BFg-etherate in benzene-ether affords in 45% yield the 6jff-fluoro-5a-hydroxy-derivative (36) and its 3-ethylene ketal, respectively. which are converted into the 6a-fluoro-A -CH3... 

However, suitably located hydroxyl and acetoxyl functions can assist the cisoid approach of the peracid reagent. While 4jS-acetoxycholest-5-ene gives a 9 1 ratio of the a- and jS-epoxides, the 4a-acetoxy-5-ene yields the a-epoxide exclusively. The directive effect can be used to prepare and /9-oxiranes from A -steroids as illustrated by the epoxidation of (16) and (18). 

Another unusual directive effect has been observed in the epoxidation of A -double bonds, which in most cases takes place predominantly on the a-side, e.g. 23. However, when carbon-17 is sp hybridized, epoxidation gives exclusively the -epoxide e.g., 25). 

Henbest and Jackson have rationalized these remote directive effects on the basis of the well-supported mechanism of alkaline epoxidations. The initial step in the reaction is the reversible addition of the hydroperoxide ion... 

An oxirane formed by the direct epoxidation, which usually occurs from the sterically least hindered side of the molecule, can be converted into its stereoisomer by a reaction sequence which involves the diaxial opening (in acetic acid at 100° for 2 hr) of the epoxide to a diol mo noacetate. Subsequent mesylation followed by treatment with base gives the inverted oxirane, as shown for the sequence (69) (70) (71) (72). ... 

Among the more exotic methods which have been used for the direct epoxidation of steroid olefins are chromic acid, ozone, e.g., (84), and photochemical oxygenation. Ozone is useful for the epoxidation of the unreactive 8,9-olefin, but the results of the other unusual methods can usually be duplicated by the methods of epoxidation discussed above. 

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. 

Conversion of an epoxide directly to an acetonide is accomplished with acetone and SnCl4 (81-86% yield) or with A-(4-methoxybenzyl)-2-cyan- opyridinium hexafluoroantimonate [A-(4-MeOC6H4CH2)-2-CN-PyrSbFJ (59-100% yield). ... 

In addition, the cyclopentylidene ketal has been prepared from dimethoxy-cyclopentane, TsOH, CH3CN, or cyclopentanone (PTSA, CUSO4 >70% yield) and can be cleaved with 2 1 ACOH/H2O, rt, 2 h. Certain epoxides can be converted directly to cyclopentylidene derivatives as illustrated in the following reaction ... 

Cyclic carbonates are prepared directly from epoxides with LiBr, CO2, NMP (l-methyl-2-pyrrolidinone), 100°. ... 

The product of nucleophilic attack can be anticipated by examining the lowest-unoccupied molecular orbital (LUMO) on protonated cyclopentene oxide. From which direction (top or bottom) would a nucleophile be more likely to approach each epoxide carbon in order to transfer electrons into this orbital Explain. Does one carbon contribute more to the LUMO, or is the orbital evenly spread out over both epoxide carbons Assuming that LUMO shape dictates product stereochemistry, predict which stereoisomers will be obtained, and their approximate relative amounts. Is the anticipated kinetic product also the thermodynamic product (Compare energies of 1,2-cyclopentanediol stereoisomers to tell.)... 

Stereoselective epoxidation can be realized through either substrate-controlled (e.g. 35 —> 36) or reagent-controlled approaches. A classic example is the epoxidation of 4-t-butylcyclohexanone. When sulfonium ylide 2 was utilized, the more reactive ylide irreversibly attacked the carbonyl from the axial direction to offer predominantly epoxide 37. When the less reactive sulfoxonium ylide 1 was used, the nucleophilic addition to the carbonyl was reversible, giving rise to the thermodynamically more stable, equatorially coupled betaine, which subsequently eliminated to deliver epoxide 38. Thus, stereoselective epoxidation was achieved from different mechanistic pathways taken by different sulfur ylides. In another case, reaction of aldehyde 38 with sulfonium ylide 2 only gave moderate stereoselectivity (41 40 = 1.5/1), whereas employment of sulfoxonium ylide 1 led to a ratio of 41 40 = 13/1. The best stereoselectivity was accomplished using aminosulfoxonium ylide 25, leading to a ratio of 41 40 = 30/1. For ketone 42, a complete reversal of stereochemistry was observed when it was treated with sulfoxonium ylide 1 and sulfonium ylide 2, respectively. ... 

Directing influence of functional groups and geometry of reactant molecules on the peroxide epoxidation of alkenes 99UK206. 

Hydroxy group directivity in the epoxidation of chiral allylic alcohols 99ACR703. 

---