Alkenes, epoxidation secondary reactions

The reaction between epoxides and ammonia (or ammonium hydroxide) is a general and useful method for the preparation of (3-hydroxyamines. With epoxide derived from terminal alkenes, the reaction with ammonia gives largely the primary amine, but secondary and tertiary amine products are possible from the appropriate epoxide. The reaction of 121 with ammonium hydroxide with microwave irradiation, for example, gave 122. Ethanolamines, which are useful solvents... 

Although the final yields of ketone are not high, i.e. they range from 50 to 67%, the reaction is very useful because it can be carried out on substrates with several other functional groups. For example, the reaction is successful when acetals, thioacetals, lactones, non-conjugated alkenes, epoxides, alcohols, and secondary bromides are present in the alkyne. 

Iodosylarenes other than iodosylbenzene have also been used in the transition metal catalyzed oxidation reactions. The soluble o-(tert-butylsulfonyl)iodosylbenzene (Section 2.1.4) can serve as an alternative to iodosylbenzene in (porphyrin)manganese(III)-catalyzed alkene epoxidation reactions [718]. A convenient recyclable reagent, w-iodosylbenzoic acid, can selectively oxidize primary and secondary alcohols to the... 

Autoxidation of alka-2,4-dienals accompanied by retroaldolisa-tion leads temporarily to epoxides and finally to relatively stable end products. Similarly to alk-2-enals, the main reaction products include alkanals, alkenals, dialdehydes (including malondialde-hyde) and hydrocarbons. Some secondary reactions of alka-2,4-dienals are shown in Figure 3.53. 

The method is quite useful for particularly active alkyl halides such as allylic, benzylic, and propargylic halides, and for a-halo ethers and esters, but is not very serviceable for ordinary primary and secondary halides. Tertiary halides do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and elimination predominates. The reaction can also be applied to activated aryl halides (such as 2,4-dinitrochlorobenzene see Chapter 13), to epoxides, " and to activated alkenes such as acrylonitrile. The latter is a Michael type reaction (p. 976) with respect to the alkene. 

To date, the most frequently used ligand for combinatorial approaches to catalyst development have been imine-type ligands. From a synthetic point of view this is logical, since imines are readily accessible from the reaction of aldehydes with primary or secondary amines. Since there are large numbers of aldehydes and amines that are commercially available the synthesis of a variety of imine ligands with different electronic and steric properties is easily achieved. Additionally, catalysts based on imine ligands are useful in a number of different catalytic processes. Libraries of imine ligands have been used in catalysts of the Strecker reaction, the aza-Diels-Alder reaction, diethylzinc addition, epoxidation, carbene insertions, and alkene polymerizations. 

Photoepoxidation of alkenes with oxygen in the presence of photosensitizers266-268 can be used as a synthetic method. The complete absence of any nucleophile in the reaction mixture prevents secondary transformations of the formed oxirane and thus allows the preparation of sensitive epoxides. 

Ketones from halohydrins. Palladium acetate complexed with a triarylphos-phine, particularly tri-o-tolylphosphine, converts halohydrins into ketones in the presence of K2C03. Yields are about 70-85% for substrates in which the halogen is secondary or tertiary, but less than 50% when the halogen is primary because of epoxide formation. The reaction is useful for conversion of alkenes to ketones in those instances in which halohydrins are formed regioselectively. 

Iodine-catalysed hydroperoxidation of cyclic and acyclic ketones with aqueous hydrogen peroxide in acetonitrile is an efficient and eco-friendly method for the synthesis of gem -dihydroperoxides and the reaction is conducted in a neutral medium with a readily available low-cost oxidant and catalyst.218 Aryl benzyl selenoxides, particularly benzyl 3,5-bis(trifluoromethyl)phenyl selenoxide, are excellent catalysts for the epoxidation of alkenes and Baeyer-Villiger oxidation of aldehydes and ketones with hydrogen peroxide.219 Efficient, eco-friendly, and selective oxidation of secondary alcohols is achieved with hydrogen peroxide using aqueous hydrogen bromide as a catalyst. Other peroxides such as i-butyl hydroperoxide (TBHP), sodium... 

The rate constants for oxidation of a series of cycloalkenes with ozone have been determined using a relative rate method. The effect of methyl substitution on the oxidation of cycloalkenes and formation of secondary organic aerosols has been analysed.155 Butadiene, styrene, cyclohexene, allyl acetate, methyl methacrylate, and allyl alcohol were epoxidized in a gas-phase reaction with ozone in the absence of a catalyst. With the exception of allyl alcohol, the yield of the corresponding epoxide ranged from 88 to 97%.156 Kinetic control of distereoselection in ozonolytic lactonization has been (g) reported in the reaction of prochiral alkenes.157... 

The most important catalytic asymmetric syntheses include addition reactions to C=C double bonds. One of the best known is the Sharpless epoxidations. Sharpless epoxidations cannot be carried out on all alkenes but only on primary or secondary allylic alcohols. Even with this limitation, the process has seen a great deal of application. 

The aminocyclitol moiety was synthesized in a stereocontrolled manner from cis-2-butene-l,4-diol (Scheme 40)112 by conversion into epoxide 321 via Sharpless asymmetric epoxidation in 88% yield.111 Oxidation of 321 with IBX, followed by a Wittig reaction with methyl-triphenylphosphonium bromide and KHMDS, produced alkene 322. Dihydroxylation of the double bond of 322 with OSO4 gave the diol 323, which underwent protection of the primary hydroxyl group as the TBDMS ether to furnish 324. The secondary alcohol of 324 was oxidized with Dess-Martin periodinane to... 

A catalytic method which promises to find wide application in view of its mildness and ease of execution uses a catalytic amount of tetra-n-propylammonium perruthenate (TPAP) with A7-methylmorpholine -oxide (NMO) as the cooxidant. ° l4imary (and secondary) alcohols which contain a range of ftinc-tional groups (alkenes, tetrahydropyran ethers, epoxides, lactones, silyl ethers and indoles inter alia) can be oxidized without interference by the other functional group (equations 21-23). The performance of the reagent is improved further by including molecular sieves in the reaction mixture. ... 

The discussion to this point has focused entirely on the epoxidation of allylic (and homoallylic) alcohols catalyzed by the [Ti(OR)2(tartrate)] complex. The role of the alkene as a nucleophile towa the activated peroxide oxygen in Ais reaction has been established (see Section 3.2.6). If the alkene of the allylic alcohol is replaced by another nucleophilic poup then, in principle, oxidation of that group may occur (equation 8). In practice, oxidations of this type have b n observed and generally have been carried out with a substrate bearing a racemic secondary alcohol so that kinetic resolution is achieved. While these oxidations are not strictly within the scope of this chapter, they are summarized briefly in... 

Where functional groups are present which are more readily oxidized than the ether group, multiple reactions can occur. For example, in their total synthesis of (-i-)-tutin and (-i-)-asteromurin A, Yamada et al. observed concomitant oxidation of a secondary alcohol function in the oxidation of the ether (30) with ruthenium tetroxide (equation 24). The same group successfully achieved the simultaneous oxidation of both ether functions of the intermediate (31) in their related stereocontrolled syntheses of (-)-picrotox-inin and (-i-)-coriomyrtin (equation 25). Treatment of karahana ether (32) with excess ruthenium tetroxide resulted in the formation of the ketonic lactone (33) via oxidation of both the methylene group adjacent to the ether function and the exocyclic alkenic group (equation 26). In contrast, ruthenium tetroxide oxidation of the steroidal tetral drofuran (34) gave as a major product the lactone (35) in which the alkenic bond had been epoxidized. A small amount of the 5,6-deoxylactone (17%) was also isolated (equation 27). This transformation formed the basis of a facile introduction of the ecdysone side chain into C-20 keto steroids. 

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