Síntese de α-metileno-β-lactamas via ciclização intramolecular de n-propiolamidas catalisada por t-BuOK e sua funcionalização via arilação de Heck catalisada por paládio

Abstract

The present work describes the regio- and stereoselective synthesis of α-methylene-β-lactams through intramolecular cyclization of different N-propiolamides catalyzed by potassium tert-butoxide. The same, in catalytic amounts of 30 mol%, together with dimethylformamide and dimethyl sulfoxide as solvents, proved to be efficient for the promotion of this cyclization. The optimized condition found for the synthesis of β-lactams in the present study, describes the use of 30 mol% of potassium tert-butoxide and 3 mL of dimethyl sulfoxide for 0.25 mmol of the corresponding N-benzyl-N-methyl-3-phenylpropiolamide, under heating at 90°C for 1 hour. The application of these conditions to other N-propiolamides, provided 16 examples of derivatives of the β-lactam ring, with yields between 33-87%. These showed a good tolerance to the use of removal groups and electronic density donors in both aromatic portions. In addition to their synthesis, the functionalization of these β-lactams through Heck arylation is later described, which was catalyzed by palladium acetate and made use of different aryl iodides, leading to the obtaining of 8 new examples of polysubstituted β-lactams with yields between 41-86%.