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 molecular 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 Et(3)N as a base are necessary to achieve a complete conversion of the starting material. The reaction is feasible in various solvents such as DMF, acetonitrile, and THF. The desired new Se-N heterocycles 15 and 21 were isolated under optimized conditions in yields of 82 and 68%, respectively. Experiments have been conducted with various copper(I) and copper(II) salts, a chloroamine 17, an aryl bromide 18, and an N-acylated amine 19 to show the scope and the limitations of 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 findings, which were obtained during the optimization process of this new introduction of selenium.
Erdelmeier
I
I
OXIS International SA, 1 place Boieldieu, 75002 Paris, France. erdelmeier@aol.com
Tailhan-Lomont
C
C
Yadan
J C
JC
D003300:Copper / Q000737:chemistry*; D005979:Glutathione Peroxidase / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D018716:Molecular Mimicry; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D012643:Selenium
D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D003300:Copper; D005979:Glutathione Peroxidase; D012643:Selenium