Allylic alcohol dehydration

When used at room temperature in the presence of an active platinum catalyst in an inert solvent, e.g., acetone or ethyl acetate, oxygen will oxidize nonhindered, saturated hydroxyl groups and exposed allylic alcohols. This reagent has found extensive use in sugar chemistry and is particularly suited for the selective oxidation of either 3a- or 3j -alcohols of steroids. Other hydroxyl groups on the steroid skeleton are much less sensitive to oxidation. As a result, this reaction has been used extensively in research on polyhydroxy cardiac-active principles, e.g., the cardenolides and bufadienolides, where the 3-hydroxyl group is easily oxidized without extensive oxidation or dehydration of other hydroxyl groups. The ordinarily difficult selective oxidation of the... 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

Another interesting example of dehydrative C-C coupling involves the alkylation of benzimidazole 36 with allyl alcohol 37, which is catalysed by complex 39 [15], The reaction is believed to proceed by alkene complex formation with the allyl alcohol 37 with loss of water from the NH proton of the NHC ligand and OH of the allyl alcohol to give an intermediate Ji-allyl complex. The initially formed 2-allylbenzimidazole isomerises to a mixture of the internal alkenes 38 (Scheme 11.9). 

Scheme 11.9 Dehydrative coupUng of a benzimidazole with allyl alcohol...

With ethylenic hydrocarbons, as seen on p.237, it is rather difficult to know whether a dangerous reaction is due to the instability of the double bond or its polymerisation. Allylic alcohol dehydration is one example. Alcohols treated in a sulphuric acid medium can form, according to the conditions and the alcohol structure, either an ethylenic hydrocarbon or an ether. 

The enol ethers of P-dicarbonyl compounds are reduced to a, 3-unsaturated ketones by LiAlH4, followed by hydrolysis.115 Reduction stops at the allylic alcohol, but subsequent acid hydrolysis of the enol ether and dehydration leads to the isolated product. This reaction is a useful method for synthesis of substituted cyclohexenones. 

Several methods and reaction pathways have been reported for the conversion of glycerol in the literature, such as etherification, esterification [1], and oxidation [2], Via ionic dehydration acetol [3] and acrolein can be produced. The radical steps result in aldehydes, allyl alcohol, etc. [4], If the dehydration is followed by a hydrogenation step, propanediols (1,2- or 1,3-) can be obtained [5-6]. 

Metallocyclopentenes are frequently formed in photochemical reactions of the Group 14 metal alkyls or catenates in the presence of dimethylbutadiene. This class of compound also has an extensive photochemistry82. For example, photolysis of 51 (R = H or Me) produced the allylic alcohols 52 and 53 and, for R = H, 54. These alcohols could be dehydrated over AI2O3 to give the germole 55 along with other diene compounds. 

Ruthenium catalysts have also been used in this context.200,201 In particular, the cationic ruthenium complex, CpRu(CH3CN)3PF6, in conjunction with carboxylic acid ligand 3, has been used to achieve the remarkably chemoselective allylation of a variety of alcohols via dehydrative condensation with allyl alcohol (Equation (50)).202 It is worth noting that this transformation proceeds with 0.05 mol% catalyst loading and does not require the use of excess allyl alcohol. 

In a previous section, the effect of plasma on PVA surface for pervaporation processes was also mentioned. In fact, plasma treatment is a surface-modification method to control the hydrophilicity-hydrophobicity balance of polymer materials in order to optimize their properties in various domains, such as adhesion, biocompatibility and membrane-separation techniques. Non-porous PVA membranes were prepared by the cast-evaporating method and covered with an allyl alcohol or acrylic acid plasma-polymerized layer the effect of plasma treatment on the increase of PVA membrane surface hydrophobicity was checked [37].The allyl alcohol plasma layer was weakly crosslinked, in contrast to the acrylic acid layer. The best results for the dehydration of ethanol were obtained using allyl alcohol treatment. The selectivity of treated membrane (H20 wt% in the pervaporate in the range 83-92 and a water selectivity, aH2o, of 250 at 25 °C) is higher than that of the non-treated one (aH2o = 19) as well as that of the acrylic acid treated membrane (aH2o = 22). 

Similarly, 5-lactols and 5-lactones are obtainable from the corresponding homo allylic alcohols. With dehydration, the corresponding dihydropyrans are prepared. Spirocyclic y-butyrolactones of this type and the corresponding 5-lactones are widespread in nature and play a key role as synthetic intermediates. 

Similarly, allenes [32] and alkynols [33] were used as starting materials and their carbonylation provides /3,y-unsaturated acids and unsaturated diacids, respectively. The specific reactivity of alkynols is explained by three formal steps during nickel catalysis (i) carbonylation of the triple bond leading to an acid containing an allylic alcohol moiety (ii) second carbonylation of the double bond to provide a hydroxydiacid and (iii) a dehydration step giving the corresponding unsaturated diacid (Scheme 2). 

Next, the TMS enol ether of 53c underwent oxidation with MCPBA to trimethylsilyloxy ketone 57. in 86% yield (86% conversion). Addition of methylmagnesium bromide in methylene chloride proceeded in almost quantitative yield (95%) to give tertiary alcohol 58. Dehydration with Burgess reagent [19] and acidic workup provided the allylic alcohol 59a in 63% yield, which was converted... 

Allylic and homoallylic alcohols are particularly susceptible to oxidation and dehydration. Hiskey and Oxley successfully nitrated both allyl alcohol and l-buten-4-ol with nitronium tetrafluoroborate in diethyl ether at -71 °C. 

This beneficial effect of fluorination on hydrolytic stability has also been demonstrated with the synthetic prostaglandin SC-46275 (Fig. 70). This compound possesses an anti-secretory activity that protects the stomach mucous membrane. However, its clinical development was too problematic because of the instability of the tertiary allyl alcohol in acidic medium (epimerisation, dehydration, etc.). A fluorine atom was introduced on the C-16 methyl to disfavour the formation of the allylic carbocation. This fluorinated analogue possesses the same biological activity, but does not undergo any degradation or rearrangement, and itepimerises only slowly [165]. 

The full paper on the synthesis of onikulactone and mitsugashiwalactone (Vol. 7, p. 24) has been published.Whitesell reports two further useful sequences (cf. Vol. 7, p. 26) from accessible bicyclo[3,3,0]octanes which may lead to iridoids (123 X=H2, Y = H) may be converted into (124) via (123 X = H2, Y = C02Me), the product of ester enolate Claisen rearrangement of the derived allylic alcohol and oxidative decarboxylation/ whereas (123 X = 0, Y = H) readily leads to (125), a known derivative of antirride (126) via an alkylation-dehydration-epoxi-dation-rearrangement sequence. Aucubigenin (121 X = OH, R = H), which is stable at —20°C and readily obtained by enzymic hydrolysis of aucubin (121 X = OH, R = j8-Glu), is converted by mild acid into (127) ° with no dialdehyde detected sodium borohydride reduction of aucubigenin yields the non-naturally occurring isoeucommiol (128 X=H,OH) probably via the aldehyde (128 X = O). ... 

One of the first optically active allenes reported was synthesized by enantioselective dehydration of a racemic allylic alcohol in the presence of (+)-10-camphorsulfonic acid as the chiral catalyst125,126. The initial optical rotation of the tetraarylallene is low, but can be increased to [a],2/1 +351 (cyclohexane) after several recrystallizations. 

Preparation by Ring Expansion of Cyclododecanone. Radical addition of allyl alcohol to cyclododecanone, for example, with di-/cr/-butyl peroxide as a radical initiator, yields 2-(7-hydroxypropyl)cyclododecanone. This is converted into 13-oxabicyclo[10.4.0]hexadec-l(12)-ene by acid-catalyzed dehydration [202], Addition of hydrogen peroxide, in the presence of sulfuric acid, gives 12-hydroperoxy-13-oxabicyclo[10.4.0]hexadecane. Cleavage of the peroxide by heating in xylene gives 15-pentadecanolide as well as a small amount of 15-pentadec-l l(and 12)-enolide and 12-hydroxy-15-penta-decanolide [203]. 

Dehydration of alcohols, diols, or glycols does not give allenes in appreciable yield because conjugated dienes [30] are the main product. Even allyl alcohol cannot be suitably dehydrated to allene in reasonable yields. When elimination to the conjugated diene is prevented, as for 2,2-dimethyl-4-hexene-3-ol, the allene is still obtained in only 19% yield [31]. 

An intramolecular photocyclization catalyzed by copper(I) triflate provided a key step in a total synthesis of the ginseng sesquiterpenes a- and /J-panasinsene, (8) and (9). The unsaturated allylic alcohol (6) is cyclized by irradiation at 254 tun in the presence of CuOTf to a mixture of saturated alcohols, which is oxidized to the ketone 7. The ketone is inert to methylenetriphenylphosphorane, but can be converted into a 2 5 mixture of 8 and 9 by addition of mcthyllithium followed by dehydration.2... 

At lower temperatures and with a variety of catalysts [LiaPOs, CrsO, SnOa, UOj, and others) it ie possible to cause allyl alcohol to become the principal isomerization product-676-1063 Still other catalysts e g. CdO-CdCIs or WOa-FejsOj on dehydrated chromia) are known to lead almost exclusively to propionaMehyde.6 4... 

That enone formation accompanies allylic alcohol can be explained by the known oxidizability of alcohols on irradiated semiconductor surfaces (288) or by dehydration of an intermediate allylic hydroperoxide. 

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