The addition of a nucleophile to a carbonyl group is one of the most important C-C bond forming processes. The diasteroeselectivity of this nucleophilic attack has generally been explained using steric factors; however, this explanation is still controversial due to electronic interactions (hyperconjugation) between the carbonyl group and adjacent groups. In our studies of the phenomenon of face selection in addition and elimination processes, we have made much use of 5-substituted adamantan-2-ones and their derivatives as probes. We have found it possible to account for our observations by assuming that the transition states are stabilized by hyperconjugative donation of electrons into the δ* orbital of the newly forming or breaking bond by the antiperiplanar vicinal bonds. When two of these vicinal bonds are adjacent to an electron-withdrawing substituent as in 1-X, they are rendered electron-poor by it; the two transition states are then unequal in energy, and as a result, syn attack (as in 2-a) is favored. We have found that the ratios are larger when the electron demand of X is greater and where the trigonal carbon carries a positive charge. It therefore occurred to us that we might be able to increase the selectivity of ketones by modifying either the carbonyl function or the group X at C-5 so as to make them more electron demanding. One such possible way to influence diastereoselectivity is the deliberate addition of one of the more traditional Lewis acids. A good example is the complex of 1-Ph with antimony pentachloride. The increased charge at C-2 is clear from its deshielding (by 25 ppm relative to the pure ketone), the increased C=O bond length (by 0.045 Å), and the shift in the carbonyl on the infrared spectrum. The reduction of this complex produced the E-alcohol in excess (65:35) when compared to the E/Z alcohol ratio of the free ketone (57:43). Similar results were obtained by adding various Lewis acids. Drawing from this data, it can be postulated that the activated carbonyl group by metal complexation enhanced the carbocation character of the carbonyl C atom resulting in preferred resonance structures where certain bonds are better donors. Currently, we are working with admantan-2-ones with donating groups at C-5. The compounds being utilized as donating groups include SiMe3 and SnMe3. These electronic interactions have resulted in a reverse effect than their withdrawing counterparts, producing the Z-alcohol in excess.

Lewis-acid enhanced face selection in the reduction of adamantanones

ACS Spring 2022

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