Reduction adamantanones

The fact that some electronic effect is operative in adamantanone reductions and the general preference for an axial approach in cyclohexanones initiated detailed investigations (by... 

Studies of adamantanone reduction have been interpreted by le Noble [8 a, 8 b, 9] as consistent with the Cieplak hypothesis, since the reaction occurs preferentially from the face opposite the more electron-rich cr-bond. The Cieplak hypothesis considers interactions of adjacent c-bonds adjacent to the transition state with the cr orbital of the forming C-Nu bond (see Fig. 6-18). Figure 6-19 shows that the mixing of the adjacent antiperiplanar C-D (D=donor) with the (7 c-nu ot the transition state lowers the energy of the transition state. 

Typical preparation of naphthopyran 32 involves Fries rearrangement of 1-acetoxynaphthalene 30. Condensation of 2-acetyl- 1-naphthol 31 with adamantanone, followed by usual reduction and dehydration gives 32 (Scheme 16).70... 

Gibb, W., Jeffery, J. Reduction of the non-steroid adamantanone by crystalline preparations of cortisone reductase. Biochem. J. 126, 443 (1972). 

Some further examples of the reduction of adamantanones have highlighted that increasing the positive dipole on the C=0 using Lewis acids, or placing charged substituents at C(5) within the adamantyl framework, enhances face selectivities in borohydride and aluminium hydride reductions due to Cieplak effects. 

Hahn and le Noble have discovered strongly enhanced stereoselectivity in the reduction of 5-substituted adamantanones where the substitution at C5 is by positive nitrogen (Hahn, J. M. le Noble, W. J., J. Am. Chem. Soc., 1992, 114, 1916). Thus E/Z ratios for borohydride reduction of compounds 1-3 were in the range 20-25. Suggest a possible reason for these observations on the basis of orbital interaction theory. 

Dehydroadamantanes are most readily obtained from either carbene insertion reactions or from 1,3-reductive eliminations. Pyrolysis of the dry sodium salt of the tosylhydrazone of adamantanone gives good yields of 2,4-dehydroada-mantane 133>. The unstable 1,3-dehydroadamantane is obtained from the treatment of 1,3-dibromoadamantane with sodium (Eq. (43)) 134>. 

The rates of nucleophilic additions to adamantanone have been studied in an attempt to determine the structure of the transition states of nucleophilic additions to carbonyl compounds in general. The kinetic analysis suggests that the transition states of borohydride reductions of ketones are product-like while for bisulfite additions the transition states are reactant-like 367). A similar analysis 36 ) of data obtained for photo-initiated oxetane formation (trans-dicyanoethylene + carbonyl compound) 3681 indicates a reactant-like transition state. 

On p. 1023, it was mentioned that electronic effects can play a part in determining which face of a carbon-carbon double bond is attacked. The same applies to additions to carbonyl groups. For example, in 5-substituted adamantanones (2) electron-withdrawing (-/) groups W cause the attack to come from the syn face, while electron-donating groups cause it to come from the anti face. In 5,6-disubstituted norborn-2-en-7-one systems, the carbonyl appears to tilt away from the 7i-bond, with reduction occurring from the more hindered face. An ab initio study of nucleophilic addition to 4-ferf-butylcyclohexanones attempted to predict 7i-facial selectivity in that system. ... 

The photolyses of 2-aziadamantane (16) within CyD hosts give product distributions that largely depend on the type of CyD and thus the supramolecular structure. The formation of 2,4-didehydroadamantane (22) is essentially precluded when other inter- and innermolecular reaction channels are available. However, the formation of 22 is greatly enhanced within supramolecular coniines. The amount of reduction to hydrocarbon 2, the share of azine 19 and 2-adamantanone, the formation of CyD ethers 25a and 25b, and the insertion into solvent molecules yielding 25c-e can widely be controlled by geometry and composition of the ICs. This very interesting influence of the host as mediator can be observed especially well for the photolyses of 16, which primarily yield carbene 21—a species that has no intramolecular pathways to stabilization. 

The results of experiments on the reduction on 5-substituted adamantanones 1 and 5-azaadamantan-2-one N-oxide (2) with NaBHq show that electron-withdrawing substituents favour attack by the complex hydride syn to the substituent or nitrogen [30, 34, 51] (Fig. 6-17). In the case of 2, the effect is striking, with a synlanti attack ratio of 96/4 for the formation of the anti syn alcohols respectively (Table 6-1). Electron-donating substituents show a marginal preference for anti attack. Similarly, syn facial selectivity is found in free-radical reactions [63], ther-... 

Figure 6-17. Facial selection observed in the reduction of 2-adamantanones with NaBH4.

Calculations on the Reduction of 5-Substituted Adamantanones with AlHj 177... 

Figure 6-22. Transitions structure geometry for reduction of adamantanone (1 X=H) with AlHj.

However, the stereoselective reductions of the 5-substituted adamantanones 3.50 [CT2, G5, KA4, LL5], and bicyclo-[2.2.2]-octan-2-one 3.51 [MK5] have been interpreted in terms of Cieplak s model [C6, CT3]. Unfortunately, the observed stereoselectivities are low (de <40%), so that it is difficult to dissect the various parameters involved in such reductions [CHS, N2], The electronic contribution to the stereoselectivity of the reduction of substituted 9-benzonorbomenones 3.52 is very important [G5, OTl, OT2] (Figure 3.20). Halogen substituents on the aromatic ring favor syn attack by all hydrides on those very rigid systems. Electrostatic effects have been invoked to interpret these results [PW2, WTl]. 

Twistanone (147) was found peculiar in its outstanding inertness toward these microbial reductions, and this reluctance was also found in D2(j bisnor-adamantanone (163), though to a lesser extent. This has been attributed to the presence of the protruding methylene group opposite the carbonyl function across the twist-boat cyclohexane ring. 

The 5-substituted 2-adamantanones constitute a class of molecules belonging to the category of 4-substituted cyclohexanones. William le Noble studied the reduction of several of this class of compounds by different hydride sources and noted the selectivity profile. These results are collected in Table 5 [18]. Although the reaction conditions are not exactly the same for direct comparison of the results... 

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