Noradamantanes, 2-substituted

Protoadamantanone is a versatile intermediate for the synthesis of not only protoadamantane derivatives,but also 1,2- and 2,4-disubstituted adamantanes, ° 2-substituted noradamantanes," and 4(5)-substituted 4-homoprotoadamantanes. ... 

In addition to the facile aluminum halide and sulfuric acid catalyzed rearrangement routes to noradamantane and substituted noradamantanes discussed above (see Eq. (11) and Scheme 8), a variety of ring closure reactions have also been employed for the preparation of these systems. The most useful reaction for this purpose involves a transannular ring closure of the bicyclo [3.3.1 Jnonyl system. Thus, 7-methyl-3-noradamantanol is obtained 12°) from the treatment of 3-keto-7-methylenebicyclo[3.3.1 jnonane 121) with sodium in moist ether (Eq. (36)). 

An extremely easy synthesis of 3-substituted noradamantanes is derived from the cleavage of the 2-methyl-2-adamantyloxy radical. Pyrolysis of 2-... 

The single Favorskii ring contraction of 1,5-dibromoadamantane-2,6-dione (55) also enables the preparation 3-substituted noradamantanes as illustrated in Eq. (40) 126>. Unfortunately, the starting material, 55, is diffi-... 

Similar symmetry problems confront the substitution reactions of other systems, e.g. noradamantane, homoadamantane and ethanoadamantane. Nor-adamantane, for example, may be brominated when treated with bromine under vigorous conditions but a difficult to separate mixture of bromides results72. At the present time, derivatives of noradamantane (see also Scheme 8), homoadamantane, and related systems are most readily obtained by more indirect methods as discussed in Section III. Bromination of ethanoadamantane (25) gives a single monobromide, however 38b). 

Protoadamantanone is a versatile intermediate for the synthesis of not only protoadamantane derivatives,but also 1,2- and 2,4-disubstituted adamantanes, 2-substituted noradamantanes, and 4(5)-substituted 4-homoprotoadamantanes. 4-Protoadamantanone has been prepared by the nitrous acid deamination of 2-amino-l-adamantanol (77%), by aprotic diazo-tization of endo-7-aminomethylbicyclo[3.3.1]nonan-3-one in benzene with an equivalent amount of acetic acid (67%), and by thermolysis of 1-adamantyl hypohalites followed by base-promoted cyclization of the resulting halo ketones (32-37%).In spite of low and erratic yields, the last reaction sequence has provided the most convenient route to the protoadamantanes, since the other two approaches require lengthy syntheses of the starting materials. 

Various thiolans have been prepared by ionic hydrogenation of thiophens with EtjSiH in the presence of acids. Addition of singlet oxygen to alkyl-substituted thiophens, followed by reduction with di-imine, gave the bicyclic compounds (42) these are examples of the hardly known thia-ozonides. 9-Thia-noradamantane (43) has been synthesized from cyclo-octa-2,7-dienone by a reaction sequence involving a transannular C—H carbene insertion. A bicyclic product (44) has been obtained by the reaction of (—)-carvone with... 

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