1. Substitution of N-alkoxyimidoyl fluorides by carbon nucleophiles
Debra D. Dolliver, Southeastern Louisiana University, Hammond, Louisiana
The oxime ether moiety in a single geometric configuration is becoming important in many pharmaceutical and agricultural compounds and as a starting material in the synthesis of chiral amines. Current synthetic routes to this moiety offer little or no control of the E/Z stereochemistry and generally require a difficult separation of geometric isomers.
We have demonstrated that a single geometric isomer of an oxime ether can be formed from nucleophilic substitution of a (Z)-N-alkoxyimidoyl fluoride by a Grignard reagent. These reactions give moderate to good yields of an oxime ether with exclusively retained stereochemistry (Scheme 1). This synthetic route eliminates the need for separation of geometric isomers which is inherent in most other methods that introduce the oxime ether moiety.
We have also completed studies on nucleophilic substitution of N-alkoxyimidoyl fluorides by enolate-type ions. These substitutions result in novel carbon acids which display varying degrees of imine-enamine tautomerism (Scheme 2). This study adds to our understanding of the impact of electron-withdrawing groups and aromatic rings on the stability of the imine versus the enamine tautomer. The work outlined in Schemes 1 and 2 has resulted in a full paper, coauthored by two undergraduate researchers, which is currently in press in the Canadian Journal of Chemistry.
Scheme 1
Scheme 2