Rearrangements of Epoxides

Epoxides are reactive, versatile intermediates in organic chemistry [1,2], The epoxidation of olefins and subsequent rearrangement in the presence of acidic or basic catalysts is widely used for the preparation of aldehydes, ketones, ethers, or alcohols. The reactions are used for the synthesis of a variety of fine chemicals and are conventionally catalyzed with homogeneous catalysts such as metal halides or mineral acids. Substitution of these homogeneous systems by heterogeneous catalysts is, however, becoming increasingly attractive because they are readily separated from the product and do not usually cause environmental problems. 

Acidic activation of the epoxide can be achieved either by Brpnsted-acidic catalysis via addition of a proton to the epoxide oxygen or by Lewis-acidic catalysis via coordination of the epoxide oxygen to a multivalent cation. In basic catalysis one of the epoxide carbons is attacked by a nucleophile. Only acid-catalyzed ringopening leads to an intermediate carbocation (3) which can easily result in the mi- 

In contrast, heterogeneous catalysts are readily separated from the products this is essential for fine chemicals such as fragrances, flavors, pharmaceuticals, or their precursors, because they are intended for human consumption and so have to meet the highest standards of quality. 

For this reason heterogeneous catalysts such as Si02, AI2O3, ZnO, and WO, supported metals and a variety of precipitated phosphates have been tested for epoxide rearrangement reactions. Use of these conventional catalysts often results in the formation of aldol condensation products and mixtures of ketones and aldehydes as by-products. The heavier molecules formed by aldol condensation are the first step in the formation of coke thus limiting the lifetime of these catalysts. 

A further advantage of heterogeneous catalysts is, that they can be used in gas-phase reactions so that continuous processes can be created with relatively low technical (equals financial) effort. 

Rearrangements of epoxides and their derivatives under the presence of Lewis acids are valuable tools in the synthesis of carbonyl compounds. Kita and coworkers have recently shown that the rearrangement of six membered 2,3-epoxy alcohols (45) in the presence of nonchelating Lewis acids such as BF3 OEt2 gave the 5-membered ring P-hydroxy ketone (46). In contrast, the same reaction under the influence of SnCU gives a six membered a-hydroxy ketone (47) (Equation 30) [32]. 

The same authors showed that this type of rearrangement is applicable to the case of acyclic 2,3-epoxy alcohols, such as (48), to give P-hydroxy ketone (49) (Equation 31) [32]. 

Hegedus and coworkers have shown that the reaction of optically active a-oxazolidinonylallenylstannanes (50) with oxiranes, in the presence of BF3 OEt2, produces the p-hydroxypropargylamines (51) with high syn diastereoselectivity (Equation 32) [33]. Here, the Lewis acid is responsible for the rearrangement of the oxiranes to the corresponding aldehydes via alkyl, aryl or a hydride shift. 

An elegant example of BF3 OEt2-promoted epoxide ring opening was reported by Parrain and coworkers (Equation 34) [35]. This method represents the first S-exo selective oxacyclization approach toward the synthesis of bridged bis-oxocane type compounds such as (54). 

Kita and coworkers have performed a study of BF3 OEt2 promoted rearrangements of 2-aryl-2,3-epoxy acylates and have shown that cyclic 2-aryl-2,3-epoxy acylate 

Epoxide (88) is converted to C-norpregnane (89) in 60% yield by methyl-magnesium iodide in refluxing ether-benzene. No rearrangement to the C-norsteroid occurs with dimethylmagnesium. 

The steroid epoxide rearrangement can occur with Grignard reagents only if both carbons of the epoxide ring are secondary. 

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Aldehyde (41) can be made by rearrangement of epoxide (42) and the Robinson annelation gives (39) in one step. 

Acid-catalysed rearrangement of epoxides is another widely used reaction in the fine chemicals industry. Here again the use of solid acid catalysts such as zeolites is proving advantageous. Two examples are shown in Fig. 2.25 the isomerization of rsophorone oxide (Elings et al., 1997) and the conversion of a-pinene oxide to campholenic aldehyde (Holderich et al., 1997 Kunkeler etal., 1998). Both products are fragrance intermediates. 

Zeolites have also been described as efficient catalysts for acylation,11 for the preparation of acetals,12 and proved to be useful for acetal hydrolysis13 or intramolecular lactonization of hydroxyalkanoic acids,14 to name a few examples of their application. A number of isomerizations and skeletal rearrangements promoted by these porous materials have also been reported. From these, we can underline two important industrial processes such as the isomerization of xylenes,2 and the Beckmann rearrangement of cyclohexanone oxime to e-caprolactam,15 which is an intermediate for polyamide manufacture. Other applications include the conversion of n-butane to isobutane,16 Fries rearrangement of phenyl esters,17 or the rearrangement of epoxides to carbonyl compounds.18... 

K. Smith, G. A. El-Hiti, and M. Al-Shamalia, Rearrangement of epoxides to carbonyl compounds in the presence of reusable acidic zeolite catalysts under mild conditions, Catal. Lett., 109 (2006) 77-82. 

Mechanisms for nucleophilic aliphatic substitution at glycosides, 41, 277 Mechanisms of hydrolysis and rearrangements of epoxides, 40, 247 Mechanisms of oxygenations in zeolites, 42, 225 Mechanisms, nitrosation, 19, 381... 

BASE-INDUCED REARRANGEMENT OF EPOXIDES TO ALLYLIC ALCOHOLS trans-Pinocarveol,... 

TT-ALLYLNICKEL HALIDES METHALLYLBENZENE, 52, 115 Rearrangement of epoxides to allylic alcohols, 53, 17 Reduction, by controlled-po-tential electrolysis, 52, 22 by lithium aluminum hydride of exo-3,4-dichlorobicyclo [3.2.l]oct-2-ene to 3-chlorobicyclo[3.2.l]oct-2-ene, 51, 61... 

S)-(-)-CITRONELLOL from geraniol. An asymmetrically catalyzed Diels-Alder reaction is used to prepare (1 R)-1,3,4-TRIMETHYL-3-C YCLOHEXENE-1 -CARBOXALDEHYDE with an (acyloxy)borane complex derived from L-(+)-tartaric acid as the catalyst. A high-yield procedure for the rearrangement of epoxides to carbonyl compounds catalyzed by METHYLALUMINUM BIS(4-BROMO-2,6-DI-tert-BUTYLPHENOXIDE) is demonstrated with a preparation of DIPHENYL-ACETALDEHYDE from stilbene oxide. A palladium/copper catalyst system is used to prepare (Z)-2-BROMO-5-(TRIMETHYLSILYL)-2-PENTEN-4-YNOIC ACID ETHYL ESTER. The coupling of vinyl and aryl halides with acetylenes is a powerful carbon-carbon bond-forming reaction, particularly valuable for the construction of such enyne systems. 

Scheme 8.7. Mechanism of the electrochemically catalysed rearrangement of epoxides to ketones.

We have previously reported that when the rearrangement of trans-stilbene oxide was carried out with CF3SO3H, the solution turned red and the product diphenylacetaldehyde was less pure than that obtained with bismuth triflate. This observation points to the role of bismuth(III) triflate as a Lewis acid in the rearrangement of epoxides and not to protic acid catalysis by triflic acid released by hydrolysis of bismuth triflate. 

Kirk DN, Hartshorn MP (1968) Rearrangement of epoxides. In Steroid reaction mechanisms. Elsevier, Amsterdam, p 353... 

Manganese(lll) acetate oxidation of (+)-p-menth-l-ene yields the two lactones (165 X=0, Y = CH2) and (165 X = CH2, Y = O) as major products together with anticipated acetates similar oxidation of (+)-pulegone yields the C-2 acetates in low yield and oxidation of isomenthone in the presence of isopropenyl acetate results in acetonylation at C-2 and C-4. Further examples of the rearrangement of epoxides with KOBu -aprotic solvents (pyridine is favoured) have been reported (c/. Vol. 6, p. 44), e.g. (166) to (167), although with the corresponding 1,2-epoxy-... 

Enantioselective deprotonation.2 The rearrangement of epoxides to allylic alcohols by lithium dialkylamides involves removal of the proton syn to the oxygen.3 When a chiral lithium amide is used with cyclohexene oxide, the optical yield of the resulting allylic alcohol is 3-31%, the highest yield being obtained with 1. 

BASE-INDUCED REARRANGEMENT OF EPOXIDES T 0 ALLYLIC ALCOHOLS trans- PINOCARVEOL... 

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