Ab Initio Study of the Regiochemistry of Dimetalated Oximes. The Importance of Triple Ions in Isomeric Lithium and Sodium Ion Pairs of the Acetaldoxime Dianion
The potential energy surfaces of dilithioacetaldoxime and its sodium analogue have been explored at the ab initio level. Several stationary points have been located with a slightly modified 3-21+G basis set. Harmonic vibrational frequencies have been calculated to characterize the stationary points, and energies have been obtained with a slightly modified 6-31+G* basis set. The relative energies of the isomeric dimetalated derivatives of acetaldoxime show a preference for the formation of the syn-configured isomer, whereas in the case of the isolated dianion the anti isomer is thermodynamically favored by 2.2 kcal mol-1. The relative energies of the isomeric metal derivatives of acetaldoxime are in agreement with experiment. The regioselective second deprotonation at the syn α-carbon and the regioselective addition of electrophiles to the syn α-carbon are consistent with the calculated structures of the dimetalated intermediates. These results suggest that these structures of dimetalated oximes be considered in discussions of reaction mechanism. Triple ions formed by the heteroatoms and the cations are the primary structural concept. Chelation by the heteroatoms is more important than the interaction of the cations with the (formally) carbanionic methylene group. The triple ions formed between the heteroatoms and the cations differ in detail due to modes of puckering and give rise to topologically different structures. The syn preference energy for the dilithium derivatives of acetaldoxime is 4.4 kcal mol-1. Sodium increases the syn preference energy to 8.3 kcal mol-1 and suggests that larger regioselectivity may be possible by use of bases with large cations. The interactions between sodium and the heteroatoms, nitrogen in particular, are enhanced compared to lithium. Replacement of Li+ by Na+ results in structures of different topology in some cases.
R. Glaser and A. J. Streitwieser, "Ab Initio Study of the Regiochemistry of Dimetalated Oximes. The Importance of Triple Ions in Isomeric Lithium and Sodium Ion Pairs of the Acetaldoxime Dianion," Journal of Organic Chemistry, vol. 54, no. 23, pp. 5491-5502, American Chemical Society (ACS), Nov 1989.
The definitive version is available at https://doi.org/10.1021/jo00284a021
Keywords and Phrases
Acetaldoxime; Lithium Ion; Oxime; Sodium Ion; Computer Analysis; Drug Structure; Ion Binding; Nonhuman; Theoretical Study
International Standard Serial Number (ISSN)
Article - Journal
© 1989 American Chemical Society (ACS), All rights reserved.