ABSTRACT
The synthesis of carboxylate-substituted imidazoline derivatives has previously been accomplished by the condensation of presynthesized 1,2-diamines with amides, or through the transition metal catalyzed aldol-type reaction between isocyanates and imines (4,5). We have recently communicated an alternative palladium catalyzed route to synthesize a new class of imidazoline carboxylates, utilizing acid chloride, imines and carbon monoxide as starting materials (see Table 1) (6). This work was the first demonstration of a goal in our laboratory of developing metal-mediated routes to peptide-based molecules, using CO and imines as aarnino acid residue synthons. Notably, this process has the advantage of allowing for the synthesis of these heterocycles from readily available irnine, acid chloride and carbon monoxide precursors, via a four component coupling methodology. As imines are derived from a large pool of commercially available aldehydes and amines, this methodology could lend itself to the synthesis of a number of new and structurally diverse imidazoline derivatives. In this report, we explore the scope and limitations of this catalytic process as a route to prepare imidazoline carboxylates. In addition, the mechanism by which the four separate components (imines, carbon monoxide and acid chloride) are coupled into the imidazoline product is also examined (7).
