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Open Access Publications from the University of California

Assigning the Absolute Configuration of Sulfoxides and Cyclic Secondary Amines using the Competing Enantioselective Conversion (CEC) Method

  • Author(s): Valdes, Alexander
  • Advisor(s): Rychnovsky, Scott
  • et al.

Various metal-ligand catalyst systems were screened in order to determine if enantioselective oxidations were suitable as potential transformations for Competing Enantioselective Conversion (CEC) analysis. Optimization of CEC conditions allowed for analysis in the common solvent CDCl3, which minimized analysis time by avoiding a workup step. Increasing the equivalents of oxidant from 1 to 5 afforded greater difference in selectivity over a 16.5 hour time frame of the analysis, which allows for more accurate determination of absolute configuration. Synthesis of enantioenriched sulfoxides for substrate testing began using the Senanayake protocol. Initial CEC results indicated a lack of selectivity or a mismatch in selectivity that prompted the investigation of the Uemura system. The Uemura system was unreliable in our hands, and the project was ultimately abandoned.

Using the kinetic resolution data reported by the Krasnov group, a suitable pseudoenantiomeric acyl chloride bearing substitution along the aromatic ring was synthesized as a potential CEC reagent. Multi-step synthesis of heterocyclic amine substrates bearing varying substitution at the chiral center or aromatic ring was conducted to assess the scope of CEC reactivity. Initial investigations into the CEC reactions displayed mixed results, with a few substrates displaying predicted selectivity and one other displaying the opposite selectivity. Several other substrates did not display any relevant mass peaks (starting material or product) after repeated trials. A base screen showed that the inclusion of tertiary amine bases to the CEC reaction did not influence the selectivity in an appreciable manner.

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