Copper(I)-assisted mild and convenient synthesis of new Se-N heterocycles:Access to a promising class of GPx mimics

Benzisoselenazolines 15 and benzisoselenazines 21, designed as low molecula r weight mimics of glutathione peroxidases, were synthesized for the first time. Starting from amines 13 and 14, a smooth introduction of selenium in nonactivated aryl bromides using KSeCN in the presence of CuI was developed . An equimolar quantity of CuI and the presence of Et3N as a base are neces sary to achieve a complete conversion of the starting material. The reactio n is feasible in various solvents such as DMF, acetonitrile, and THF. The d esired new Se-N heterocycles 15 and 21 were isolated under optimized condit ions in yields of 82 and 68%, respectively. Experiments have been conducted with various copper(I) and copper(II) salts; a chloroamine 17, an aryl bro mide 18, and an N-acylated amine 19 to show the scope and the limitations o f this method. The previously unknown sulfur analogues 20 and 22 have been synthesized in moderate yields using a slightly modified procedure. Finally , a mechanistic scheme has been proposed to discuss some interesting findin gs, which were obtained during the optimization process of this new introdu ction of selenium.