Rearrangement to alcohols

Benzo-fused epoxides 20 (n = 1 or 2) underwent facile rearrangement to alcohols 21 (n = 1 or 2, respectively) upon treatment with LDA at room temperature in only 1 h, owing to the acidic nature of their benzylic protons (Scheme 5.7) [10]. Similarly, 3,4-epoxycyclooctene 23 gave alcohol 24 [11]. 

In contrast to these results, a preference for rearrangement through an exo-transition state has been detected in the rearrangement of several cyclic allylic sulfoxides. For example, while sulfoxide 36 rearranged to alcohol 37 with 60% ee, introduction of bulky substituents at the (i position of the ring enhanced the optical purity to 90%, as a result of further destabilization of the endo conformation (equation 21)82,84. 

Sulfide and selenide precursors for 2,3-rearrangements can be obtained stereochemically pure by chal-cogeno-etherifications (equation 78). From these precursors thio-(211) and seleno-(211) were prepared by oxidation. While the sulfoxide refused to rearrange to alcohol (212) under various conditions, the selenoxide did so even at 0 °C. Here, the extra driving force of selenoxide vs. sulfoxide rearrangements was an essential it pushed the selenoxide through a transition state obviously too sterically hindered for the less reactive sulfur analog. 

Reactions of ethers with a mobile proton Cleavage of ketones, rearrangement to alcohols s. 16, 763 ... 

The reaction of trivalent carbocations with carbon monoxide giving acyl cations is the key step in the well-known and industrially used Koch-Haaf reaction of preparing branched carboxylic acids from al-kenes or alcohols. For example, in this way, isobutylene or tert-hutyi alcohol is converted into pivalic acid. In contrast, based on the superacidic activation of electrophiles leading the superelectrophiles (see Chapter 12), we found it possible to formylate isoalkanes to aldehydes, which subsequently rearrange to their corresponding branched ketones. 

Furthei-more, the cyclization of the iododiene 225 affords the si.x-membered product 228. In this case too, complete inversion of the alkene stereochemistry is observed. The (Z)-allylic alcohol 229 is not the product. Therefore, the cyclization cannot be explained by a simple endo mode cyclization to form 229. This cyclization is explained by a sequence of (i) e.vo-mode carbopallada-tion to form the intermediate 226, (ii) cydopropanation to form 227. and (iii) cyclopropylcarbinyl to homoallyl rearrangement to afford the (F3-allylic alcohol 228[166]. (For further examples of cydopropanation and endo versus e o cyclization. see Section 1.1.2.2.)... 

Carbocations derived from the alcohol are probably the reactive species, but data concerning by-products expected with carbocationic intermediates are lacking. Rearrangement of 2-alkylaminothiazoles to 2-amino-5-alkylthiazoles may also explain the observed products 2-aminothiazole with benzyl chloride yields first 2-benz Iaminothiazole (206). which then rearranges to 2-amino-5-benzvlthiazole (207) (Scheme 130) (163. 165. 198). 

Alkene synthesis via alcohol dehydration is complicated by carbocation rearrangements A less stable carbocation can rearrange to a more sta ble one by an alkyl group migration or by a hydride shift opening the possibility for alkene formation from two different carbocations... 

Esters derived from the primary alcohols are the most stable and those derived from the tertiary alcohols are the least stable. The decomposition temperature is lower in polar solvents, eg, dimethyl sulfoxide (DMSO), with decomposition occurring at 20°C for esters derived from the tertiary alcohols (38). Esters of benzyl xanthic acid yield stilbenes on heating, and those from neopentyl alcohols thermally rearrange to the corresponding dithiol esters (39,40). The dialkyl xanthate esters catalytically rearrange to the dithiol esters with conventional Lewis acids or trifluoroacetic acid (41,42). The esters are also catalytically rearranged to the dithiolesters by pyridine Ai-oxide catalysts (43) ... 

Disubstituted and trisubstituted 3-isonitrosopyrroles rearrange to 3-acylisoxazoles under the influence of hot, dilute mineral acids. For example, isonitrosotriphenylpyrrole (436), when treated with boiling alcoholic mineral acid, is converted into 3-benzoyl-4,5-diphenyl-isoxazole (437) (62HC(17)1, p. 34). 

The treatment of 3-acylisoxazoles (438) with hydroxylamine hydrochloride gives furazan ketones (439). On the other hand, furazan ketones (439) rearrange to 3-acylisoxazoles (438) with a loss of hydroxylamine under the influence of a mineral acid. Thus, by refluxing phenacylphenylfurazan with concentrated alcoholic hydrogen chloride, 3-benzoyl-5-phenyl-isoxazole is formed similarly, phenyl(phenacylphenyl)furazan gives 3-benzoyl-3,5-diphenyl-isoxazole (62HC(17)1, p. 35). 

Formation of the 3-cyclohexeityl cation from the alcohol in superacid media is followed by more extensive rearrangement to give the methylcyclopentenyl ion, which is tertiary and allylic. ... 

Hydroxyl groups are stable to peracids, but oxidation of an allylic alcohol during an attempted epoxidation reaction has been reported." The di-hydroxyacetone side chain is usually protected during the peracid reaction, either by acetylation or by formation of a bismethylenedioxy derivative. To obtain high yields of epoxides it is essential to avoid high reaction temperatures and a strongly acidic medium. The products of epoxidation of enol acetates are especially sensitive to heat or acid and can easily rearrange to keto acetates. 

Carbocation rearrangements occur in the reactions of some secondary alco hols with DAST, thus isobutyl alcohol gives a mixture of isobutyl fluoride and tert-hxAy] fluonde [95] (Table 6), and both bomeol and isoborneol rearrange to the same 3-fluoro-2 2,3-tnraethylbicyclo[2 2 IJheptane (72-74%) accompanied by camphene [95]... 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

The benzothiazine equivalent of a 1,7 naphthyridine (58) has also been prepared. The reaction did not work in alcoholic solvents, but when DMF was used 57 rearranged to provide the desired product in moderate yield. 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

Halogenation of the 7 position also proves compatible with good antiinflammatory activity. Construction of this compound, aclomethasone dipropionate (80), starts by introduction of the required unsaturation at the 6,7 position by dehydrogenation with DDQ (76). The highly hindered nature of the hydroxyl at position 17 requires that a roundabout scheme be used for formation of the corresponding ester. Thus treatment of 76 with ethyl orthoformate affords first the cyclic orthoformate This then rearranges to the 17 ester on exposure to acetic acid. Acylation of the 21 alcohol is accomplished in straightforward fashion with... 

Interestingly, the product actually isolated from alkyne hydration is not the vinylic alcohol, or enol (ene + ol), but is instead a ketone. Although the enol is an intermediate in the reaction, it immediately rearranges to a ketone by a process called keto-enol tautomerisni. The individual keto and enol forms are said to be tautomers, a word used to describe constitutional isomers that interconvert rapidly. With few exceptions, the keto-enol tautomeric equilibrium lies on the side of the ketone enols are almost never isolated. We ll look more closely... 

The (3-elimination of epoxides to allylic alcohols on treatment with strong base is a well studied reaction [la]. Metalated epoxides can also rearrange to allylic alcohols via (3-C-H insertion, but this is not a synthetically useful process since it is usually accompanied by competing a-C-H insertion, resulting in ketone enolates. In contrast, aziridine 277 gave allylic amine 279 on treatment with s-BuLi/(-)-spar-teine (Scheme 5.71) [97]. By analogy with what is known about reactions of epoxides with organolithiums, this presumably proceeds via the a-metalated aziridine 278 [101]. 

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