Helene Lebel

The formation of C—N bonds is an important transformation in organic synthesis, as the amine functionality is found in numerous natural products and plays a key role in many biologically active compounds [1]. Standard catalytic methods to produce C—N bonds involve functional group manipulations, such as reductive amination of carbonyl compounds [2], addition of nucleophiles to imines [3], hydrogenation of enamides [4—8], hydroamination of olefins [9] or a C—N coupling reaction [10, 11]. Recently, the direct and selective introduction of a nitrogen atom into a C—H bond via a metal nitrene intermediate has appeared as an attractive alternative approach for the formation of C—N bonds [12-24]. 

Copper-catalyzed decomposition of benzenesulfonyl azide in the presence of cyclohexene was the first reported evidence of a metal-catalyzed nitrene insertion reaction [25]. This seminal discovery was then followed by the pioneering work of Breslow and Gellman who introduced the use of iminoiodinanes as metal nitrene precursors as well as rhodium dimer complexes as catalysts [26,27]. They showed the formation of the corresponding benzosultam in 86% yield in the presence of rhodium (II) acetate dimer (Rh2(OAc)4) via an intramolecular metal nitrene C—H bond insertion reaction (Eq. (5.1)). 

Muller then intensively studied rhodium dimer complexes as catalysts for the intermolecular amination of alkanes using iminoiodinanes, typically PhI=NTs and PhI=NNs [28-30]. Good yields were obtained for amination of benzyUc, aDylic and tertiary C—H bonds, which are the most reactive C— H bonds towards metal nitrenes. For instance the amination of indane provided the corresponding benzylic amine in 

69% yield (Eq. (5.2)). However, an excess of the alkane substrates is required to minimize the competitive degradation of the iminoiodinane reagent. 

High yields are obtained with iminoiodinane reagents, however, they cannot be stored and must be used immediately [15]. Moreover, they are tedious to purify, as they form polymeric structures and are insoluble in most organic solvents. Besides tosyl- and nosyl-substituted iminoiodinanes, others are almost impossible to isolate in pure form. It is to overcome these problems that one-pot processes in which the iminoiodinane species is prepared in situ rather than being isolated, have been developed. Che first demonstrated such a reaction for an intermolecular C H insertion (Eq. (5.3)) [31, 32]. The reactive metal nitrene species is generated from a mixture of the requisite amine with diacetoxyiodobenzene, in the presence of manganese porphyrin catalyst. 

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Eric A. Korf Gerald E Koser Chutima Kuhakam Brian R. Kusche Kenneth K. Laali Emmanuel Lacdte Robert W. Lang James W. Leahy Helene Lebel Salvatore D. Lepore Steven V. Ley... 

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