Nickel Mediated Radical Reactions

Abstract

The tributyltin hydride-mediated carbon-carbon bond formation via radical addition and cyclization of alkyl halides with alkenes has often been a choice for construction of various organic molecules [ 11. However, the requirement for hightemperature initiators or photo initiation and the difficulties associated with purification of the products from tributyltin halides tend to limit the widespread use of these methods, despite the efforts to make the methods easier [lc, 21. Recently, nickel-mediated radical additions and cyclizations have been introduced as promising alternatives to the tributyltin hydride methods. These are the nickel powderacetic acid method for cyclization of haloamides to y-lactams, p-lactams and indolones, the borohydride exchange resin-nickel boride method for radical addition, nickel-catalyzed electroreductive cyclization and nickel-catalyzed Kharasch addition of polyhalo compounds. The Nickel Powder-Acetic Acid MethodThe use of nickel powder in combination with acetic acid was first introduced in 1992 by Zard and coworkers [3]. It has been proven that powdered nickel in the presence of an organic acid such as acetic acid works as a very mild reducing agent capable of cleaving an oxime ester into a carboxylate anion and an iminyl radical.The key feature of this system is that the produced iminyl radical 2 is sufficiently long-lived to undergo useful radical reactions. This property was applied in a practical procedure for inverting the 13-methyl group in 17-ketosteroids [3]. Thus 17-acetoxime 1 was converted to 13-epi-ketone 3 in 59% yield (Scheme 1).This system was also found to be capable of reducing certain halogenated derivatives to form carbon-centered radicals, which can also be captured in various Radicals inb Organic Synthesis Edited by Philippe-Renaud andMukund P. Sibi