Reduction of Adamantanone:  Face Selection Induced by 4-Halo and 4,9-Dihalo Substitution

Face selectivity in the reactions of 2,4-disubstituted adamantanes and their modification by inclusion in β-cyclodextrin solutions

“…The preparation of 4-ethyleneketaladamantan-2-one (11) followed a literature procedure. 5 4.1.2. Synthesis of 4-ethylenethioketaladamantan-2-one (12).…”

“…Similar data were found for the reduction of 1-Br. 5,6 An equatorial fluoro substituent in 2-F, however, give the diequatorial alcohol 5-F and isomer 6-F in a ratio of 67:33 which resembles the face selectivity in 3-F. 1a In the sodium borohydride reduction of 7, adamantan-2-one with two equatorial b-bromosubstituents, a higher face selectivity was found (8:9Z86:14) and the results were reconciled with Cieplak's model (see Chart 1). 1a,5 Adamantane derivatives have received considerable attention because of their diverse biological activity; 7 especially when substituted with spiro-cyclopropane or spiro-pyrrolidine groups, they are known to have antiviral activity.…”

Diastereofacial selectivity in some 4‐substituted (X) 2‐adamantyl derivatives: electronic versus steric effects

“…The results of hydride reduction (NaBH 4 ) and methylation (CH 3 Li) of 4-substituted (X ax )-2-adamantanones (3, Y ¼ O; X ¼ F, Cl, Br and I) are listed in Table 1 together with those recently reported. [8] It can be seen that 4 ax -substituted (X)-2 ax -adamantanols (5, R ¼ H) and 4 ax -substituted (X) 2 eq -methyl-2 ax -adamantanols (5, R ¼ CH 3 ) are almost the exclusive products. Clearly, the results highlight the dominant role of steric effects in controlling p-face selection during nucleophilic addition to the carbonyl group.…”

“…This is well recognized and predictable. Thus, it can be seen (Table 1) that the steric factor (this includes electrostatic repulsion between the nucleophile and halogen unshared electrons in this factor) [8] of the 4-X ax substituents dominates the electronic one and directs the reagent (NaBH 4 and CH 3 Li) almost exclusively to the remote anti-face of the ketone (3,Y ¼ O). It is worth noting that a simple visualization technique based on the electrostatic potential mapped onto the LUMO with an isosurface proximal to the reactive electrophilic site accurately predicts the anti and syn face attack by nucleophiles on 3 (Y ¼ O, X ¼ F; Table 1), respectively.…”

“…The next step involves the capture of this radical with the Me 3 Sn À ion to form a radical tin anion which subsequently loses an electron to form the tin substitution product. Hence, the aforementioned stereoselectivity has its origin in the discrimination of the two faces of a common intermediate by the attacking Me 3 Sn À anion, namely, preferential anti-attack on the 4-methylene-2-adamantyl radical (8). Noteworthy, is that the preferred direction of attack is diametrically opposite to predictions (syn) based on the Cieplak model [1a] or steric accessibility (anti-approach is sterically more encumbered than syn because the nucleophile encounters two axial hydrogens for the former versus one for the latter).…”