Adamantanones stereoselectivity

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. 

Systematic examination of the catalytic properties of dimeric complexes was initiated shortly after the identification of dinuclear iron sites in metalloenzymes. The first report of a reactive dimeric system came from Tabushi et al. in 1980, who examined the catalytic chemistry of [Fe3+(salen)]20, 1 (salen is N,N -(salicylaldehydo)-l,2-ethylenediamine) (12). They reported interesting stereoselectivity in the oxidation of unsaturated hydrocarbons with molecular oxygen in the presence of mercaptoethanol or ascorbic acid and pyridine as a solvent ([l]<<[alkane]<<[2-mercaptoethanol]). With adamantane as substrate, they observed the formation of a mixture of (1- and 2-) adamantols and adamantanone (Table I) (12). Both the relative reactivity between tertiary and secondary carbons (maximum value is 1.05) and final yield ( 12 turnovers per 12 hr) were dependent on the quantity of added 2-mercaptoethanol. Because autoxidation of adamantane gave a ratio of 3°/2° carbon oxidation of 0.18-0.42, the authors proposed two coexisting processes autooxidation and alkane activation. 

Stereoelectronic effects of various remote substituents on the basicity of the carbonyl is yet another intriguing question. Electronic effects of remote substituents have been postulated to be responsible for stereoselective additions to carbonyls in rigid adamantanone systems. If present, such stereoelectronic effects would similarly be expected to bias the energetics and structural features of Lewis acid complexation. 

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]. 

Adamantanone is another ketone where interesting stereoselectivity is noted. Reduction by hydride donors is preferentially syn to acceptor substituents at C(5) and anti to donor substituents.These effects are observed even for differentially substituted phenyl groups. As the substituents are quite remote from the reaction center, steric effects are unlikely to be a factor. 

The Patemo-Buchi reaction has also received considerable attention in the past several years. Stereoselectivity in this reaction seems to be a function of both steric and electronic effects. In some cases, one is dominant over the other, but both usually play a part. For example, in the addition of disubstituted alkenes to 5-substituted adamantanones, electronics plays a more major part than sterics... 

Ring expansion of camphor (119) and adamantanone (121) derivatives under the same conditions afforded the respective (Z)-bromoiodoenones 120 and 122 in good yields and in high stereoselectivity (Scheme 3.48) [131-133],... 

Noma, Y, Y. Takahashi, and Y. Asakawa, 2003. Stereoselective reduction of racemic bicycle[33.1 Jnonane-2,6-dione and 5-hydroxy-2-adamantanone by microorganisms. Proceedings of 46th TEAC, pp. 118-120. 

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