Norbornene hydroamination

Attempts to hydroaminate ethylene, aUylbenzene, and norbornene with ArNH2 in the presence of zirconium bisamides Cp2Zr(NHAr)2 (Ar = 2,6-Me2CsH3, o-MeQH4) at temperatures up to 160°C have been unsuccessful [126]. 

A range of rhodium complexes have been studied as hydroamination catalysts. Treatment of norbornene with a mixture of aniline and lithium anilide in the presence of [Rh(PEt3)2Cl]2 at 70 °C for over 1 week yields the exo addition product in ca. 15% yield.165... 

Similar to the addition of secondary phosphine-borane complexes to alkynes described in Scheme 6.137, the same hydrophosphination agents can also be added to alkenes under broadly similar reaction conditions, leading to alkylarylphosphines (Scheme 6.138) [274], Again, the expected anti-Markovnikov addition products were obtained exclusively. In some cases, the additions also proceeded at room temperature, but required much longer reaction times (2 days). Treatment of the phosphine-borane complexes with a chiral alkene such as (-)-/ -pinene led to chiral cyclohexene derivatives through a radical-initiated ring-opening mechanism. In related work, Ackerman and coworkers described microwave-assisted Lewis acid-mediated inter-molecular hydroamination reactions of norbornene [275]. 

A few examples are known using homogeneous transition-metal-catalyzed additions. Rhodium(III) and iridium(III) salts catalyze the addition of dialkylamines to ethylene.302 These complexes are believed to activate the alkene, thus promoting hydroamination. A cationic iridium(I) complex, in turn, catalyzes the addition of aniline to norbornene through the activation of the H—N bond.303 For the sake of comparison it is of interest to note that dimethylamino derivatives of Nb, Ta, and Zr can be used to promote the reaction of dialkylamines with terminal alkenes.304 In this case, however, C-alkylation instead of /V-alkylation occurs. 

Intermolecular hydroamination or hydroarylation reactions of norbornene and cyclo-hexadiene carried out with catalytic amounts of Brpnsted or Lewis acid in ionic liquids have been found to provide higher selectivity and yields than those performed in classical organic solvents. This effect was attributed to the increases of the acidity of the medium and stabilization of ionic intermediates through the formation of supramolec-ular aggregates with the ionic liquid.38... 

A different catalytic cycle for alkene hydroamination is initiated by the oxidative addition of the N-H bond to the metal, followed by insertion of the alkene into the metal-nitrogen bond and reductive elimination to form the amine. The oxidative addition of unactivated N-H bonds to platinum(O) complexes is thermodynamically unfavorable, so the catalytic cycle cannot be completed17, but the successful iridium(I)-catalyzed amination of norbornene with aniline has been reported18. 

The diastereoselective addition of aniline to norbornene was accomplished using a catalytic amount of iridium(I). As the intermediate azametallacyclobutane 2 could be isolated its stereochemistry was determined by X-ray analysis both iridium and nitrogen occupy the exo position41. However, the scope of the amination method, with respect to the nature of the amine and the structure of the alkene, was not determined. Conversely, the analogous rhodium(I)-cat-alyzed reactions of norbornene and aromatic amines gave mixtures of hydroamination and hydroarylation products106. 

Equation 11.6. Iridium catalyzed asymmetric hydroamination of norbornene [26]. 

Earher mechanistic studies by Milstein on a achiral Ir catalyst system indicated that the iridium catalyzed norbornene hydroamination involves amine activation as a key step in the catalytic cycle [27] rather than alkene activation, which is observed for most other late transition metal catalyzed hydroamination reactions [28]. Thus, the iridium catalyzed hydroamination of norbornene with aniline is initiated by an oxidative addition of aniline to the metal center, followed by insertion of the strained olefin into the iridium amido bond (Scheme 11.4). Subsequent reductive elimina tion completes the catalytic cycle and gives the hydroamination product 11. Unfor tunately, this catalyst system seems to be limited to highly strained olefins. 

The intermolecialar hydroamination has also received some attention and studies in this area have focussed on the use of iridium and nickel catalysts. Enan-tioselectivities for the intermolecular process are also generally moderate with ees observed between 60 and 70%. The highest enantioselectivities for this reaction have been obtained during the hydroamination of norbornene (2.145) with aniline in the presence of the iridium complex (2.184) and the fluoride ion source... 

However, others have shown that oxidative additions of much less acidic substrates, such as water, ° alcohols, unactivated anilines and azole heterocycles, " occur to low-valent transition metal complexes. For example, iridium(I) complexes containing tri-ethylphosphine as ligand undergo oxidative addition of water rapidly at room temperature (Equation 7.17). Both [Ir(PEtj)J and [Ir(PEt3)jCl] also add aniline rapidly at room temperature (Equation 7.17). The latter reaction is a step in the catalytic hydroamination of norbornene. These substrates react readily with early metal complexes, but tliese reactions do not occur by oxidative addition. ... 

Scheme 15.73 Ir-phosphine-catalyzed asymmetric hydroamination with norbornene and aniline.

Compared to the hydroamination of alkynes, the protocols for more readily available olefins were rather limited. Ackermann presented a TiCU-catalyzed hydroamination reaction of norbornene using a variety of functionalized amines. Regioselective hydroarylation occurs as a competing reaction and the chemose-lectivity for hydroamination products ranges from poor to excellent [312]. This protocol can also be utilized in the hydroamination of vinylarenes with some electron-deficient amines [313] and the hydroamination of enyne compound. In the latter reaction, a subsequent rearrangement gives rise to a tetrahydroisoquinoline derivative (Scheme 14.134). 

Iridium The intermolecular hydroamination of unactivated C=C bonds in ct-olefins (RCH=CH2) and bicycloalkenes (norbornene and norbornadiene) with arylamides (ArCONH2) and sulfonamides has been attained upon catalysis by chiral iridium complexes (PP)IrHCl(NHCOAr)(NH2COAr) [PP = chiral bidentate diphosphine]. Mechanistic studies identified the product of N-H bond oxidative addition and coordination of the amide as the resting state of the catalyst. Rapid, reversible dissociation of the amide precedes reaction with the alkene, but an intramolecular, kinetically significant rearrangement of the species occurs before the reaction with alkene. ... 

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