Effect of Remote Substitution on Face Selection in Addition Reactions of Nor- and Homoadamantan-9-ones and of Several Analogues

Abstract

The effects of 3-halo substitution on face selection in borohydride reductions of both nor-and homoadamantan-9-ones 1-X and 3-X, respectively, have been compared with those of 5-halo substitution in the parent 5-haloadamantan-2-ones 2-X. The differences between the product ratios in these three compounds are small, but the selectivity of 2-X is somewhat larger than that of either of the homologues. This is also true of the corresponding aza-and diazaadamantanones, and of an electrophilic addition. It is concluded that the approach angle of the reagent is not a sensitive variable in addition reactions of cyclohexanone and its derivatives, and that well-aligned antiperiplanar bonds are preferred to achieve maximal remote substituent induced selectivities.

The Exterior Frontier Orbital Extension Model

“…Extensive studies on π-facial stereoselection of adamantan-2-ones − may offer a unique opportunity to test the utility of the EFOE model. le Noble adopted the adamantanone system as an ideal probe to delineate electronic effects on π-facial stereoselection in the absence of steric effects and conformational uncertainties.…”

“…Only electronic effects arising from a remote substituent at C-5 would be expected to be of importance in the conformationally rigid and sterically unbiased carbon framework. The 2-adamantanone derivatives studied thus far are 5-substituted adamantan-2-ones ( 20a ; X = C), 5-azaadamantan-2-ones ( 20b − d ; X = N), adamantan-2-thiones ( 21 ), 4,9-substituted adamantan-2-ones ( 22 ),43a perfluoroadamantan-2-ones ( 23 ),43b noradamantanones ( 24 ), and homoadamantan-9-ones ( 25 ) . They tentatively rationalized the observed stereoselectivity in terms of the Cieplak hyperconjugation model .…”

Total Synthesis of (±)-Aspergilline A

“…To complete the synthesis, 19 was exposed to sodium phenyl selenide in THF to produce an intermediate carboxylic acid which, upon peracetylation and Hundsdiecker iodinative decarboxylation, provided an intermediate iodide ( 20 ) that was advanced to the natural product via reductive deiodination and acetate methanolysis. − Overall this final sequence was performed without purification of intermediates and produced (±)-aspergilline A ( 1 ) as the only isolable product in 7% yield over the five steps (ca. 59%/step).…”

Face Selection in Addition and Elimination in Sterically Unbiased Systems

“…Thus, the E / Z ratios for the alcohols obtained by sodium borohydride reduction of 47 and 39 are 87:13 and 96:4, respectively, and those of 48 and 49 are 88:12 and 83:17, respectively. We assume that this trend is due to the more nearly perfect antiperiplanarity of the substituent with the bonds vicinal to it . One additional point of interest is that both methylation and reduction of the azanoradamantanone show the same solvent dependence as does the azaadamantanone itself, and surely for the same reason: donation by the unshared nitrogen pair in THF, and electron withdrawal by the nitrogen in a hydrogen-bonding medium such as methanol.…”