Hydroamination mechanistic studies

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 insertion approach is very successful in the hydroamination of alkynes and alkenes catalyzed by lanthanide complexes developed by Marks et al. [220]. Thorough mechanistic studies have been undertaken for the intramolecular reaction (hydroamination-cyclization of aminoalkenes), although the intermolecular version of the process is also efficient [222]. The mechanism of the reaction can be represented in a simplified way by Scheme 6.68. The insertion step is almost thermoneutral, but the protonolysis of the M-aminoalkyl bond that follows is exothermic and provides the necessary driving force. The insertion of the alkene into the Ln-N bond is irreversible and rate determining and it goes through a... 

A nickel-catalyzed hydroamination of acrylonitrile using cationic pincer complexes has been described (Scheme 3-109). Mechanistic studies suggested that a simple Lewis acidic role of nickel may be responsible for the catalysis in this group... 

Reznichenko AL, Hampel F, Hultzsch KC. Kinetic resolution of aminoalkenes by asymmetric hydroamination a mechanistic study. Chem. Eur. J. 2009 15(46) 12819-12827. 

A-Alkylation of amides and amines and dehydrative -alkylation of secondary alcohols and a-alkylation of methyl ketones " have been carried out by an activation of alcohols by aerobic oxidation to aldehydes, with copper(II) acetate as the only catalyst. A relay race process rather than the conventional borrowing hydrogen-type mechanisms has been proposed for the aerobic C-alkylation reactions, based on results of mechanistic studies. A Winterfeldt oxidation of substituted 1,2,3,4-tetrahydro-y-carboline derivatives provides a convenient and efiflcient method for the synthesis of the corresponding dihydropyrrolo[3,2-fc]quinolone derivatives in moderate to excellent yields. The generality and substrate scope of this aerobic oxidation have been explored and a possible reaction mechanism has been proposed. Direct oxidative synthesis of amides from acetylenes and secondary amines by using oxygen as an oxidant has been developed in which l,8-diazabicyclo[5.4.0]undec-7-ene was used as the key additive and copper(I) bromide as the catalyst. It has been postulated that initially formed copper(I) acetylide plays an important role in the oxidative process. Furthermore, it has been postulated that an ct-aminovinylcopper(I) complex, the anti-Markovnikov hydroamination product of copper acetylide, is involved in the reported reaction system. Copper(I) bromide... 

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. ... 

Only a limited number of organoactinide catalysts have been investigated for the hydroamination/cyclization of aminoalkenes (Fig. 4, Table 2) [55, 96-98]. The constrained geometry catalysts 11-An (An = Th, U) show high activity comparable to the corresponding rare earth metal complexes and can be applied for a broad range of substrates [55, 96, 97]. The ferrocene-diamido uranium complex 12 was also catalytically active for aminoalkene cyclization, but at a somewhat reduced rate [98]. Mechanistic studies suggest that the actinide-catalyzed reaction occurs via a lanthanide-like metal-amido insertion mechanism and not via an imido mechanism (as proposed for alkyne hydroaminations), because also secondary aminoalkenes can be cyclized [55, 98]. 

Although detailed mechanistic studies have not yet been performed, it is noteworthy that the reaction exhibits first order rate with respect to the concentration of catalyst and both reagents. This feature remarkably contrasts lanthanide-catalyzed intermolecular hydroamination of alkynes [20] and base-catalyzed intermolecular hydroamination of ethylene with secondary amines [152], which were both first order with respect to the concentration of the alkene/alkyne and the catalyst, but zero order in amine. 

The formation of alkyne oligomers that are concomitantly formed in the hydroamination reactions catalyzed by the thorium complexes indicates that two possible different complexes can be considered as active, conceivably with inter-conversion causing the occurrence of the two parallel processes. The discernment between these two most probable mechanistic pathways to find the key organometallic intermediate, responsible for the hydroamination process, was achieved by kinetic and thermodynamic studies (Scheme 5). The first pathway proposed the insertion of an alkyne into a metal-imido (M=N) bond, as observed for early transition metal complexes [101]. The second pathway suggested the insertion of an alkyne into a metal-amido bond, as found in some lanthanide compounds [39, 58, 84, 85]... 

Hydrazinediido complexes have been identified as active species in the titanium-catalyzed hydrohydrazination [12] and iminohydrazination of alkynes and the subsequent transformation of the hydrazones into indoles or tryptamine derivatives (Scheme 13.5) [13]. The postulated reaction mechanism of the group 4 metal-catalyzed reaction is based on the extensively studied mechanistic scheme for hydroaminations of alkynes, in which imido complexes are the key active species. 

The mechanism of the group 4 metal-catalyzed hydroamination of alkynes (Scheme 4) and allenes has been thoroughly investigated in detailed kinetic and mechanistic [41 6] as well as computational studies [47, 48]. The catalytically active species is believed to be a metal imido complex, which undergoes a reversible, rate-determining [2 + 2]-cycloaddition with an alkyne, respective allene, to yield an azametallacyclobutene species. Subsequent protonolysis leads to the imine hydroamination product. Isolation and characterization of intermediate azacyclobutene species, which are catalytically competent themselves, is a strong support of the mechanism [41,43,49-51]. Although no direct experimental [52, 53]... 

In tenns of understanding the mechanistic aspects involved in such additimis on vinylic substrates via organometallic catalysts, analogies have been drawn to the hydroamination reactimis [28-30], Chiral metal complex-promoted asymmetric hydroaminations have been proposed to follow two different pathways. The first involves a sequence that commences with the oxidative addition of the N-H bond onto the metal ion followed by the insertion of the olefin and subsequent reductive elimination of the chiral substrate. An alternative pathway has also been proposed which involves the nucleophilic attack by the free amine on a coordinated olefin and a final protonolysis sequence, which leads to the release of the final product. Similar studies on metal irm-induced hydrophosphinations have been reported, and the mechanisms suspected to be in play include those proposed by Glueck and coworkers which basically involves the oxidative addition of a secondary phosphine followed by an olefin insertion [31], Togni and coworkers have also observed in certain scenarios the coordination of the olefin to the catalyst metal center followed by the addition of a secondary phosphine across the C-C double bond [32]. 

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