Dynamic Aspects of the Stereochemistry of Metalated Oxime Ethers. An Ab Initio Study of the Pathways for Coordination Isomerization, for Syn/Anti Isomerization, and for Racemization of the Lithium Ion Pairs from Acetaldoxime


The pathways to isomerization between the chiral lithium ion pairs of acetaldoxime carbanion have been explored. The configuration of each ion pair is classified using two descriptors. In equilibrium structures one descriptor suffices to describe the configuration of each structure, but both descriptors are necessary for the recognition and consideration of all a priori possible pathways for racemization. Coordination isomerizations and racemizations of the syn- and the anti-configured ion pairs are discussed as special cases of the more general eight-minima scenario representing the epimers of two coordination isomers and their enantiomers, and the syn/anti isomerization is treated separately. This eight-minima scenario is described by a graph representation that reflects that the pathways for any pair of isomerizations X ⇄ Y and X' ⇄ Y' are enantiomerically related. Of all of the possible one-step isomerizations in this scenario only racemizations have the potential to involve achiral transition states since the enantiomerically related pathways X ⇄ X' might be identical. A systematic search for the transition-state structures for coordination isomerization and racemization is described on the basis of the symmetry properties of the imaginary vibrational modes of the achiral structures. Entirely chiral pathways for racemization exist if the corresponding achiral structure is a second-order saddle point and one of the imaginary modes fulfills the so-called IPD condition. The optimal geometries of all reasonable achiral structures have been characterized by vibrational normal mode analysis. In cases where the achiral structure is a second-order saddle point, the adjacent transition states have been located. The racemization of the η2-NO-bond coordinated anti-configured ion pair involves entirely chiral pathways, but the potential energy surface in the bifurcating region is extremely flat. The syn/anti isomerization most likely involves rotation of the HO group around the CN axis, and the transition-state structure for this pathway has been located. All of these processes occur with only small barriers and should be facile. Thus, any of the structures is readily available as a reaction intermediate or as a building block for ion-pair aggregates. Mechanistic implications are discussed with regard to possible face selectivity of the electrophile entry. The small barrier to coordination isomerization has significant consequences for the design of strategies for regio- and stereoselective CC-bond formation at the α-carbon of diastereoisomeric metalated oxime ethers.



Keywords and Phrases

Acetaldoxime; Drug Structure; Nonhuman

International Standard Serial Number (ISSN)

0002-7863; 1520-5126

Document Type

Article - Journal

Document Version


File Type





© 1989 American Chemical Society (ACS), All rights reserved.

Publication Date

01 Nov 1989