Alcohols fragmentation

Previous work by Holton [15] on the synthesis of taxane ring systems, indicated that the preparation of the bicyclo[5.3.1]undecane skeleton lies basically on the work of Biichi on patchouli alcohol [16], which led him to the development of the so-called "epoxy alcohol fragmentation" [15a]. 

Hydroxy acids provide characteristic mono or diol synthons whereas amino acids are the natural source for 1,2-amino alcohol fragments. A stereogenic center in either configuration, with methyl brandling, may be obtained from (S)-3-hydroxy-2-methylpropanoic acid, whereas quaternary dimethyl-substituted carbons with adjacent stereogenic centers are available from the degradation of camphor or a-pincnc. 

The sequence with oxazole 73 also proves to be applicable to systems in which the double bond of the allylic alcohol fragment is incorporated into a heteroaromatic ring, such as in furfuryl alcohol (77a) and thiophene-2-methanol (77b).28 After hydrolysis of the oxazolone ring with water, V-benzoyl-3,3,3-trifluoro-2-(2-methyl-3-furyl)alanine (79a) and /V-benzoyl-3,3,3-trifluoro-2-(2-melhyl-3-thienyl)alanine (79b) are obtained. The 2-methylene helerocyclcs 78 originally formed in the Claisen rearrangement undergo rearomatizalion under the reaction conditions. 

The structure on the left is in fact a complete molecule with no open valences hence, it is rejected as the alcohol fragment. The fragment on the right however seems plausible. 

Step 3 Conversion of the alcohol fragment to the alkyl halide. (Does not occur with phenols.)... 

Esters have been prepared in 63-73% yields from several simple cycloalkyl and aryl alkyl ketones by reaction at room temperature with per-benzoic acid. The larger radical of the ketone appears as the alcohol fragment of the ester. Cyclic ketones are oxidized by potassium persulfate and sulfuric acid to esters from which o>-hydroxy aliphatic esters are obtained upon hydrolysis and reesterification. Peracetic acid in acetic anhydride converts salicylaldehyde to o-hydroxyphenyl formate (88%). ... 

Unsaturated acetals can be prepared by the acetalization of an unsaturated aldehyde. Acrolein diethyl acetal, CHj=CH — CH(OCHjCH,)j, is prepared in this manner and also by the dehydrohalogenation of /3-chlo-ropropionaldehyde diethyl acetal (cf. method 20) however, the former method has definite advantages in that it involves a single-step process and gives a more stable product. The double bond may also be in the alcohol fragment, as In acetaldehyde diallyl acetal,... 

Imino-l,3-selenazolidines have been prepared using potassium selenocyanate thus, 2-imino-l,3-selenazolidines 86, 87 resulted from reactions of 0-methanesulfonyl /3-amino alcohol hydrochlorides. The products retained the chirality introduced by the amino alcohol fragment (Equations 25 and 26) <2005BML1361, 2005TL233, 1997TA3903>. 

Thus, the reaction with aromatic aldehydes is second order in aldehyde and first order in hydroxide ion,31 and no deuterium becomes attached to carbon in the alcohol fragment when the reaction is carried out in deuterium oxide solution.32 It is interesting that when the reaction is carried out with benzaldehyde in the cold and in the absence of excess alkali, benzyl benzoate has been isolated.33 Although the point has not yet been settled, it seems probable that the ester is formed by a secondary reaction between the benzylate ion which is formed initially (XXIII) and two molecules of benzaldehyde 2M0... 

Figures 4 and 5 show the tert-butanol TPReac results over the WZ and HY catalysts respectively. The m/e = 59 is the most important alcohol fragment The WZ catalyst is characterized by desorption with reaction to olefins almost exclusively (m/e values of 41 and 55). The ratio of masses 41 to 55 is consistent with the isobutene MS pattern throughout the whole tert-butanol TPReac spectmm over WZ. In heavier olefins (e.g., octenes), the m/e = 55 is the dominant fragment, which would have made extensive oligomerization easily detectable. On the other hand, the HY catalyst showed a richer tert-butanol TPReac pattern. Olefin oligomerization over HY was also evident by the asymmetry of the m/e 41 and 55 peaks. Note that if the two signals were only due to isobutene, we should expect them to follow exactly the same trend. However, Fig. 5 shows that m/e = 55 becomes more...

The replacement of the 3-phenoxybenzyl alcohol fragment by 2-methyl[1,1 -biphenyl]-3-yl leads to an increase in initial and residual foliar activity in the alkyl aryl oxime ethers. An unanticipated result was the activity of these oxime ethers as soil insecticides. The corresponding 3-phenoxybenzyl alcohol oxime ethers were inactive as soil insecticides. The results of a structure activity relationship study revealed biological activity is enhanced by electron withdrawing substituents. 

Another competitive situation is encountered with the chrysanthemic alcohol 72 which can choose between a methyl and a hydroxymethyl group for its migrating hydrogen. As it turns out, the methyl substituent wins over the hydroxymethyl, no 77, which could be formed via transition state 74, being produced. Rather than providing 73 (which was only isolated in < 5 %) this, 7-unsaturated alcohol fragmented (in a retro-ene mode) by way of 75 and 76 to formaldehyde and a 3 1 mixture of the dienes 78 and 79. 

Conjugate addition of the complete allylic alcohol fragment is possible with the mixed cuprate reagents 33 prepared by asymmetric reduction (chapter 26) of acetylenic ketones 29 to give the alcohols 30, protection as a silyl ether 31 and hydroboration-iodination. Lithiation and reaction with hexynyl copper (I) gives the mixed cuprate 33 from which the less stable anion is transferred selectively to an enone.3 This approach has been widely used in the synthesis of prostaglandins. 

Such ring systems occur in many natural products of pharmacological interest. The same catalyst system was also successfully used for the RCM of an ester unsaturated in both the acid and alcohol fragment. Thus, the 5-heptenyl ester of 10-dodecenoic acid gave an unsaturated macrocyclic lactone (7) which, on hydrogenation afforded the natural product exaltolide (1,15-pentadecanolide), a perfume ingredient (Eq. 18). 

The molecular ions obtained from alcohols fragment so readily that few of them survive to reach the collector. As a result, the mass spectra of alcohols show small molecular ion peaks. Notice the small molecular ion peak at m/z = 102 in the mass spectrum of 2-hexanol (Figure 13.8). 

Displacement of the alcoholic fragment from form (B) of the complex by-ethyl alcohol from the vapor phase would 3deld allyl alcohol. Displacement of acetaldehyde from the resulting complex by acrolein would yield acetaldehyde and the starting complex ... 

Epoxide opening Tertiary alcohols are obtained from the reaction of lithium [P-ffj-trimethylsilylvinylJtrimethylgallate with 1,1-disubstituted epoxides. The MEM-ethers of these alcohols fragment to give ketones on contact with TiCl4. The behavior is different from that of the (Z)-isomers, which form dihydropyrans. 

The intensity of the molecular ion peak in the mass spectrum of a primary or secondary alcohol is usually rather low. The molecular ion peak may be entirely absent in the mass spectrum of a tertiary alcohol. Fragmentation involves the loss of an alkyl group or the loss of a molecule of water. 

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