A One-Pot Tandem Synthesis of Sulfoximine-Based Urea From Organic Acid via Curtius Rearrangement

We develop a tandem protocol to synthesize unsymmetrical sulfoximine-based urea via Curtius rearrangement. The aliphatic/aromatic acid in the presence of diphenylphosphorylazide (DPPA) undergo Curtius rearrangement, and subsequent nucleophilic attack with sulfoximine provides corresponding urea derivative in very good to excellent yield. The protocol is equally applicable for gram-scale synthesis. The direct use of cheap, easy handling, commercially available aliphatic/aromatic acids are the main advantages of this method. Additionally, we synthesize the sulfoximine analogue of key biologically active compounds, such as tolbutamide, chlorpropamide, and oncolytic sulfonyl urea.

Automated summary

We developed a tandem protocol for synthesizing unsymmetrical sulfoximine-based urea through Curtius rearrangement. The method is applicable for gram-scale synthesis, with high yields and the advantage of using cheap starting materials. Additionally, we synthesized several important biologically active sulfoximine analogues.