Norbomene hydroamination

Ruthenium complexes mediate the hydroamination of ethylene with pyridine.589 The reaction, however, is not catalytic, because of strong complexation of the amine to metal sites. Iridium complexes with chiral diphosphine ligands and a small amount of fluoride cocatalyst are effective in inducing asymmetric alkene hydroamination reaction of norbomene with aniline [the best enantiomeric excess (ee) values exceed 90%].590 Strained methylenecyclopropanes react with ring opening to yield isomeric allylic enamines 591... 

A series of rhodium and platinum compounds have been tested in the hydroamination of norbomene with aniline, as shown in Scheme 9.36.[141] Selectivity and activity were highly dependent on the nature of the ionic liquid, but were always superior to those observed in THF. Solvents with chloride anions led to essentially no catalytic activity, whereas [PF6] or Br afforded some catalysis. Nonetheless, even with the best solvent/catalyst combination, less than 40 turnovers are achieved after 6 days at 140°C. 

Significant progress is being made in catalytic N-C bond formation. Thus, the stereoselective hydroamination of styrene derivatives [119] and norbomene [120] was achieved with BINAP catalysts (Pd and Ir, respectively) (cf. eq. (18)). 

Hydroamination. The chiral BINAP-IrCl dimer induces the enantioselective addition of aniline to norbomene (95% ee) at 75°. The reaction is facilitated by fluoride ions I activity increase by 6.5-fold). 

Scheme 11.4 Proposed mechanism for iridium catalyzed hydroamination of norbomene via amine activation.

Intermolecular hydroamination of alkynes, which is a process with a relatively low activation barrier, has not been used for the synthesis of chiral amines, since the achiral Schiff base is a major reaction product. However, protected aminoalkynes may undergo an interesting intramolecular allylic cyclization using a palladium catalyst with a chiral norbomene based diphosphine ligand (Eq. 11.9) [115]. Unfor tunately, significantly higher catalyst loadings were required to achieve better enantioselectivities of up to 91% ee. 

In other cases, the properties of fluoride ligands have been exploited to generate more active catalysts than are obtained in the absence of added fluoride or with other halogen ligands. As described in Chapter 16, added fluoride accelerates the rate of the iridium-catalyzed hydroamination of norbomene with aniline. The origin of this effect has not been revealed. 

Examples of the insertions of alkenes or alk5mes into metal-amido bonds are also rare. Examples of the insertions of alkenes into tihe M-N bonds of isolated amido complexes include the reaction of a rhodium anilide complex with alkenes to form imines witii kinetic behavior that is consistent with migratory insertion,and the formal insertion of the strongly electrophilic acrylonitrile into a platinum anilide. Additional examples include reactions of a lanthanide-amido complex generated in situ, a catalytic carboamination process in which the stereochemistry implies insertions of olefins into amides, and a catalytic hydroamination that appears to occur through an aminoalkyl complex generated by S3m addition of the iridium and amido groups across the C=C bond of norbomene. 

Hydroaminations of alkenes have proven to be more challenging to develop than other hydroamination reactions, although some of the first hydroaminations were additions to alkenes. In 1971 Coulson reported the addition of secondary amines to ethylene catalyzed by RhClj. Additions of amides to ethylene and propylene have been published more recently by Widenhoefer, as shown in Equation 16.57, and the addition of aniline to norbomene was published by Milstein and Casakiuovo. Although the turnover numbers for the addition of aniline to norbomene were low, several important mechanistic findings resulted from this work were presented in Chapter 9 and are reviewed in Section 16.5.3.3. Additions of amines to ethylene, propylene, and norbomene are less complicated than additions to higher olefins because these alkenes cannot undergo isomerization to a less reactive internal olefin. Nevertheless, Brunet has reported additions of arylamines to ethylene and hexene catalyzed by platinum halides with acid additive in anionic liquid (Equation 16.58). ... 

As discussed in Chapter 9, the insertion of olefins and alk)nes into metal-amido complexes is limited to a few examples. Such insertion reactions are proposed to occur as part of the mechanism of the hydroamination of norbomene catalyzed by an iridium(I) complex and as part of the hydroamination of alkenes and alkynes catalyzed by lanthanide and actinide metal complexes. This reaction was clearly shown to occur with the iridium(I) amido complex formed by oxidative addition of aniline, and this insertion process is presented in Chapter 9. The mechanism of the most active Ir(I) catalyst system for this process involving added fluoride is imknown. 

An intermolecular hydroamination using pre-catalyst IrCl(PEt3)2(C2H4)2 (32) has been elucidated as an overall c s-addition of the N-H bond across norbomene (33) (Scheme 9) [55]. The intermediate was crystaUographicaUy characterized as complex P, which was derived from migratory insertion of 33 into Ir-N bond of O, and both of its newly formed Ir-C and C-N bonds occupied the exo-face of 33. 

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