Amino Acid-Derived trans- N-Chloroformylimidazolidinones: Scalable, Stereoselective Synthesis, Structure, and Utility.

N-acyl imidazolidinones, which are key intermediates in the stereoselective synthesis of amino acids by "self-regeneration of stereochemistry" methods, are classically made by only moderately diastereoselective methods. We now report that cyclization of pivaldimino-amides with phosgene in the presence of pyridine may be made fully diastereoselective for the trans-N-chloroformylimidazolidinones, and we detail the conformational features of the products. We show that despite the presence of the electrophilic carbamoyl chloride function the products show remarkable stability and may be deprotonated to form enolates with useful reactivity for the synthesis of amino acid derivatives.

Asymmetric and Geometry-Selective α-Alkenylation of α-Amino Acids.

Both E- and Z-N'-alkenyl urea derivatives of imidazolidinones may be formed selectively from enantiopure α-amino acids. Generation of their enolate derivatives in the presence of K+ and [18]crown-6 induces intramolecular migration of the alkenyl group from N' to Cα with retention of double bond geometry. DFT calculations indicate a partially concerted substitution mechanism. Hydrolysis of the enantiopure products under acid conditions reveals quaternary α-alkenyl amino acids with stereodivergent control of both absolute configuration and double bond geometry.