Bridgehead alcohols

REARRANGEMENT OF BRIDGEHEAD ALCOHOLS TO POLYCYCLIC KETONES BY FRAGMENTATION-CYCLIZATION 4-PROTOADAMANTANONE... 

The procedure described here is a modification of one involving the thermal fragmentation of 1-adamantyl hypoiodite and cycliza-tion of the resulting iodo ketone/ By means of this procedure, 4-protoadamantanone is obtained from 1-adamantanol with consistent yields in the range of 71 to 82% and a purity greater than 98%. This method is also applicable to the preparation of other polycyclic ketones from the related bridgehead alcohols with a-bridges of zero, one, or two carbon atoms (see Table I). 

Selective oxidations are possible for certain bicyclic hydrocarbons.285 Here, the bridgehead position is the preferred site of initial attack because of the order of reactivity of C—H bonds, which is 3° > 2° > 1°. The tertiary alcohols that are the initial oxidation products are not easily further oxidized. The geometry of the bicyclic rings (Bredt s rule) prevents both dehydration of the tertiary bridgehead alcohols and further oxidation to ketones. Therefore, oxidation that begins at a bridgehead position... 

However, in the case of rigid carbon skeletons good yields of fluorinated products can be obtained from "bridgehead alcohols" with sulfur tetrafluoride, e.g. formation of 1, 2, and 3. ... 

Oxidation of hydrocarbons with a tertiary carbon, e.g. adamantane, with lead tetraacetate in trifluoroacetic acid-dichloromethane solution, in the presence of chloride ion, gave high yields of trifluoroacetate functionahzed bridgehead alcohols [57]. Subsequent hydrolysis yielded the free bridgehead alcohols (Scheme 13.34). Another important advantage of this method is the feasible conversion of the intermediate trifluoroacetate into an amide with acetonitrile. 

The startg. ketone dissolved in methanolic 0.4%-Na-methoxide, and the product isolated after 36 hrs. bridgehead alcohol. Y 30%. K. Wiesner, V. Musil, and K. J. Wiesner, Tetrah. Let. 1968, 5643. 

The high diastereoselectivily of this triple tandem reaction can be explained by the mechanism depicted in Scheme 3.1.5. At first glance, the thermal oxy-Cope rearrangement of 99 leads to enol 100, which tautomerizes in situ to produce the ketone 101. This ketone can adopt two chair-Uke conformations at the transition state, W and X. A close examination of the transition state Z reveals a psuedo-1,3-diaxial O-allyl-ring methylene interaction. Therefore, this favors the transition state W over X as the reactive conformer to provide the enol 102. Einally, the Claisen rearrangement proceeds anti to the bridgehead alcohol at C5 to afford the desired bicycUc product 103. 

Preparation.—Halogenonium ion oxidation of alcohol carbazates (193) affords a new method for the formation of alkyl halides from alcohols under neutral conditions this procedure (Scheme 119) provides an efficient means of conversion of bridgehead alcohols, such as adamantan-l-ol, into the corresponding halides. 

In 1977, Sasaki and co-workers reported a convenient protocol for the synthesis of 4-azahomoadamantan-3-ol by treatment of the corresponding bridgehead alcohols with sodium azide in a 1 1 mixture of 57 % H2SO4 and chloroform at 0 °C (Eq. 7.1) [121]. It is noteworthy that before this publication there was no efficient method for introduction of an azido group into bridgehead positions of polycyclic... 

A larger alcohol nucleophile was then used in this reaction 1,2 3,4-Di-isopropylidene-D-galactopyranose was used instead of methanol. With this bulkier nucleophile, none of the expected disaccharide was observed. Instead, the dianhy-drosugar 9 was isolated as the major product (48%). Presumably, this product was formed by an intramolecular reaction of the bridgehead alcohol with sugar iodonium ion intermediate. None of the external nucleophile was able to react because of the sterically crowded environment. 

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