Special Techniques 1,2-, 1,4-, 2,4-, and 2,6-Disubstituted Adamantanes

While the preparation of bridgehead (mono-,di-, etc.) and methylene substituted adamantanes is extremely easy, polysubstituted adamantanes in which one of the substituents is at a methylene position are much less readily prepared. In general, special techniques must be developed for each specific substitution pattern. 

2-Disubstituted adamantanes are most frequently obtained from internal cyclization reactions of a bridgehead substituent. Thus, photolysis of the azido-formate 79 gives 80 by nitrene insertion 279). 80 may be readily hydrolyzed to 2-amino-1-adamantanol (81) 75 Subsequent oxidation gives l-hydroxy-2-ada-mantanone (82) from which other derivatives may be prepared 280 2S1). An analogous carbene insertion is initiated by the thermal decomposition of the 

Similar internal cyclizations occur when 2- (l-adamantyl)-ethanol is treated with lead tetraacetate to give the cyclic ether 83 217 283 or with HOC1 to give 84 (Eq. (70)) 2831. These reactions apparently involve hydrogen abstractions by the initially formed alkoxy radical. 

Rearrangements of substituted protoadamantyl derivatives (see Section III.A) also appear to provide attractive routes to 1,2-disubstituted adamantanes. This is illustrated by the acid catalyzed rearrangement of the isomeric 4-methyl-4-protoadamantanols to l-methyl-2-adamantanone in near quantitative yield (Eq. (71))42 76). 

Direct synthesis of the adamantane skeleton itself also provides a route to 1,2-disubstituted adamantanes. This approach is illustrated in Eq. (72) 2841. 

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