Epoxidation of alcohols

Reaction times with the catalytic method are comparable to those obtained with the stoichiometric method and Z-disubstituted allylic alcohols can be efficiently epoxidized at —20 JC in 1 -4 hours using just 5% titanium(IV) isopropoxide and 6-7.5% tartrate (Table 4). The method is especially useful for epoxidation of alcohols that react only very slowly under normal conditions. In particular, Z-disubstituted allylic alcohols (Table 4) react at useful rates only if the reaction is warmed to —10 °C. In the catalytic procedure the absence of large quantities of titanium salts and tartrate minimize epoxide opening that would be a problem in the stoichiometric procedure at this temperature. A similar situation exists for unsymmetrical disubstituted allylic alcohols (Table 4) which are also prone to opening under the conditions of the stoichiometric method. 

The bulk of oxidations with tert-butyl hydroperoxide consists of epoxidations of alkenes in the presence of transition metals [147, 215, 216, 217, 218]. In this way, a,p-unsaturated aldehydes [219] and ketones [220] are selectively oxidized to epoxides without the involvement of the carbonyl function. Other applications of tert-butyl hydroperoxide such as the oxidation of lactams to imides [225], of tertiary amines to amine oxides [226, 227], of phosphites to phosphates [228], and of sulfides to sulfoxides [224] are rare. In the presence of a chiral compound, enantioselective epoxidations of alcohols are successfully accomplished with moderate to high enantiomeric excesses [221, 222, 223]. 

Kinetic resolution of another allylic alcohol in the Sharpless epoxidation was also employed in the synthesis of (Jl)-lO and fully oxygenated AB building block 35 (Scheme 6) [47]. Epoxidation of alcohol 34 [48] followed by LAH reduction and then oxidation with the Fetizon reagent [41,49] furnished hydroxyketone (Jl)-lO. Ketahzation of the carbonyl group and subsequent stereoselective benzyUc hydroxylation, using iodosobenzene in the presence of [ 5,10,15,20-tetrakis(pentafluorophenyl)-2 lH,23H-porphine ] iron(lll) chlo-... 

An elegant de novo total asymmetric synthesis of (-l-)-DNJ, based on the RCM approach, was proposed by Poisson (Scheme 38). It was initiated from oxirane 193 (ee>99%), obtained by the Sharpless asymmetric epoxidation of alcohol 192 with subsequent Payne rearrangement. 

Prepared by epoxidation of styrene with per-oxyelhanoic acid. Reactions are similar to those of aliphatic epoxides (s e, e.g. ethylene oxide). Reacts with alcohols to give mono-ethers, e g. PhCH(0Me)CH20H. Phenols give resins. 

Regioselective epoxidation of allylic and homo-allylic alcohols... 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

Sharpless epoxidations can also be used to separate enantiomers of chiral allylic alcohols by kinetic resolution (V.S. Martin, 1981 K.B. Sharpless, 1983 B). In this procedure the epoxidation of the allylic alcohol is stopped at 50% conversion, and the desired alcohol is either enriched in the epoxide fraction or in the non-reacted allylic alcohol fraction. Examples are given in section 4.8.3. 

In all cases examined the ( )-isomers of the allylic alcohols reacted satisfactorily in the asymmetric epoxidation step, whereas the epoxidations of the (Z)-isomers were intolerably slow or nonstereoselective. The eryfhro-isomers obtained from the ( )-allylic alcohols may, however, be epimerized in 95% yield to the more stable tlireo-isomers by treatment of the acetonides with potassium carbonate (6a). The competitive -elimination is suppressed by the acetonide protecting group because it maintains orthogonality between the enolate 7i-system and the 8-alkoxy group (cf the Baldwin rules, p. 316). 

As a further application of the reaction, the conversion of an endocyclic double bond to an c.xo-methylene is possible[382]. The epoxidation of an cWo-alkene followed by diethylaluminum amide-mediated isomerization affords the allylic alcohol 583 with an exo double bond[383]. The hydroxy group is eliminated selectively by Pd-catalyzed hydrogenolysis after converting it into allylic formate, yielding the c.ro-methylene compound 584. The conversion of carvone (585) into l,3-disiloxy-4-methylenecyclohexane (586) is an example[382]. 

Although the chemical reactions of epoxides will not be covered m detail until the fol lowing chapter we shall introduce their use m the synthesis of alcohols here... 

Epoxidation of an alkene followed by lithium aluminum hydride reduction of the result mg epoxide gives the same alcohol that would be obtained by acid catalyzed hydration (Section 610) of the alkene... 

Propylene oxide-based glycerol can be produced by rearrangement of propylene oxide [75-56-9] (qv) to allyl alcohol over triUthium phosphate catalyst at 200—250°C (yield 80—85%) (4), followed by any of the appropriate steps shown in Figure 1. The specific route commercially employed is peracetic acid epoxidation of allyl alcohol to glycidol followed by hydrolysis to glycerol (5). The newest international synthesis plants employ this basic scheme. 

Displacement of activated chlorine atoms also proceeds with certain types of organic compounds, but only in the presence of Lewis acid catalysts. Particular examples include epoxides, polyhydric alcohols, trialkylphosphites (12), and P-aminocrotonates (13). These additives are commonly used in conjunction with metallic stabilizers to provide complete, high performance, commercial stabilizer packages. 

This chemical bond between the metal and the hydroxyl group of ahyl alcohol has an important effect on stereoselectivity. Asymmetric epoxidation is weU-known. The most stereoselective catalyst is Ti(OR) which is one of the early transition metal compounds and has no 0x0 group (28). Epoxidation of isopropylvinylcarbinol [4798-45-2] (1-isopropylaHyl alcohol) using a combined chiral catalyst of Ti(OR)4 and L-(+)-diethyl tartrate and (CH2)3COOH as the oxidant, stops at 50% conversion, and the erythro threo ratio of the product is 97 3. The reason for the reaction stopping at 50% conversion is that only one enantiomer can react and the unreacted enantiomer is recovered in optically pure form (28). 

Enzymatic hydrolysis of A/-acylamino acids by amino acylase and amino acid esters by Hpase or carboxy esterase (70) is one kind of kinetic resolution. Kinetic resolution is found in chemical synthesis such as by epoxidation of racemic allyl alcohol and asymmetric hydrogenation (71). New routes for amino acid manufacturing are anticipated. 

Hydroperoxide Process. The hydroperoxide process to propylene oxide involves the basic steps of oxidation of an organic to its hydroperoxide, epoxidation of propylene with the hydroperoxide, purification of the propylene oxide, and conversion of the coproduct alcohol to a useful product for sale. Incorporated into the process are various purification, concentration, and recycle methods to maximize product yields and minimize operating expenses. Commercially, two processes are used. The coproducts are / fZ-butanol, which is converted to methyl tert-huty ether [1634-04-4] (MTBE), and 1-phenyl ethanol, converted to styrene [100-42-5]. The coproducts are produced in a weight ratio of 3—4 1 / fZ-butanol/propylene oxide and 2.4 1 styrene/propylene oxide, respectively. These processes use isobutane (see Hydrocarbons) and ethylbenzene (qv), respectively, to produce the hydroperoxide. Other processes have been proposed based on cyclohexane where aniline is the final coproduct, or on cumene (qv) where a-methyl styrene is the final coproduct. 

The ratio of yy -epoxide (shown above) to ant -eipoxide is 10—25 1 with TYZORTPT catalysis, whereas vanadjdacetylacetonate is less selective and y -chloroperoxybenzoic acid gives the reverse 1 25 ratio. It is supposed that TYZOR TPT esterifies the free hydroxyl, then coordinates with the peroxide to favor yy -epoxidation (135). This procedure is related to that for enantioselective epoxidation of other allyflc alcohols in 9—95% enantiomeric excess (135). 

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). 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

Fig. 20. UV initiated cationic cure of epoxidized block copolymer in the presence of alcohol (Kraton Polymer s EKP-207 and L1203 inono-ol).

Lithium aluminum hydride (LiAlH4) is the most powerful of the hydride reagents. It reduces acid chlorides, esters, lactones, acids, anhydrides, aldehydes, ketones and epoxides to alcohols amides, nitriles, imines and oximes to amines primary and secondary alkyl halides and toluenesulfonates to... 

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