Diversity-Oriented Synthesis of 2-Iminothiazolidines: Pushing the Boundaries of the Domino Nucleophilic Displacement/Intramolecular anti-Michael Addition Process

Methods for the synthesis of a variety of functionalized 2-iminothiazolidines and related heterocycles through a base-mediated domino nucleophilic displacement/intramolecular anti-Michael addition process involving electron-deficient allylic bromides and 1,3-ambident nucleophiles derived from thiourea were developed. These transformations proceed under mild and simple conditions and different functional groups are well tolerated. The scope and limitations of this protocol are dependent on the structure of the allylic bromide and 1,3-ambident nucleophile involved. The synthetic versatility of 2-iminothiazolidines was further demonstrated through a series of chemoselective modifications, giving rise to a wide range of thiazolidine frameworks of structural complexity. In particular, the reductive cyclization of 2-nitrobenzyl-substituted 2-iminothiazolidines furnished novel spiroquinolones in good to fair yields. The structural assignment of key products was unequivocally achieved by X-ray diffraction analysis and two-dimensional NMR techniques.

Automated summary

A method for the synthesis of a variety of functionalized 2-iminothiazolidines and related heterocycles through a base-mediated domino nucleophilic displacement/intramolecular anti-Michael addition process has been developed, showing good tolerance to different functional groups. The synthetic versatility of 2-iminothiazolidines was further demonstrated through a series of chemoselective modifications, leading to a wide range of thiazolidine frameworks of structural complexity.