Alkene hydroamination mechanism

The rare earth metal-catalyzed hydroamination/cyclization of internal and terminal aminoalkynes is a facile process, as shown by experimental [28, 29] and theoretical [32] studies. In general, the reaction proceeds via the same mechanism as amino-alkene hydroamination (Scheme 2) with some notable difference arising from a different insertive reactivity of the triple bond. The insertion of the C-C triple bond proceeds much faster than that of a double bond due to the exothermic nature of the insertion step (Fig. 1). Overall, the cyclization of an aminoalkyne is commonly 1-2 orders of magnitude faster than that of an analogous terminal aminoalkene. However, the insertion step is still considered to be the rate-determining step, based on aforementioned DFT calculations and experimental observations. 

Scheme 2.15 Postulated mechanism for the copper-catalysed hydroamination of electron-deficient alkenes...

Kovacs, G., Ujaque, G. and Lledos, A. (2008) The Reaction Mechanism of the Hydroamination of Alkenes Catalyzed by Gold(I)-Phosphine The Role of the Counterion and the N-Nucleophile Substituents in the Proton-Transfer Step. Journal of the American Chemical Society, 130, 853-864. 

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]. 

The latter transformation requires the use of a small amount of an acid or its ammonium salt. By using [Cp2TiMe2] as the catalyst, primary anilines as well as steri-cally hindered tert-alkyl- and sec-alkylamines can be reacted.596 Hydroamination with sterically less hindered amines are very slow. This was explained by a mechanism in which equlibrium between the catalytically active [L1L2Ti=NR] imido complex and ist dimer for sterically hindered amines favors a fast reaction. Lantha-nade metallocenes catalyze the regiospecific addition of primary amines to alkenes, dienes, and alkynes.598 The rates, however, are several orders of magnitude lower than those of the corresponding intramolecular additions. 

The mechanism does not proceed through a direct hydroamination of one of the diastereotopic alkenes, but involves a series of very selective processes including a deprotonation of (22), diastereoselective protonation of (26), intramolecular addition of lithium amide (27) to the 1,3-diene moiety, and final regioselective protonation of the allyl anion (28), all mediated by a substoichiometric amount of n-BuLi. 

A different mechanism again is involved in the hydroamination reaction catalyzed by lanthanide complexes, Cpff.nR which is applied to the cyclization of unsaturated amines. The mechanism involves the formation of a metal amide species from both the catalysts (by different routes), followed by the turnover —limiting intramolecular insertion of the alkene to give a cr-complex, from which the decomplexed cyclic amine is obtained after reaction with a second molecule of the unsaturated amine19,20,107. 

Pioneering experimental findings by Marks and coworkers [97,103,114] followed by theoretical analysis [109] allowed elucidation of the mechanism of aminoalkene hydroamination/cyclization (Fig. 13). The reaction is considered to proceed through a rare-earth metal amido species, which is formed upon protonolysis of a rare-earth metal amido or alkyl bond. As discussed in the previous section, the first step of the catalytic cycle involves insertion of the alkene into the rare-earth metal amido bond with a seven-membered chair-like transition state (for n = 1). The roughly thermoneutral [103,109] insertion step is considered to be rate-determining, giving rise of a zero-order rate dependence on substrate concentration and first-order rate dependence on catalyst concentration. 

The mechanism and scope of rare-earth metal-catalyzed intramolecular hydrophosphination has been studied in detail by Marks and coworkers [147,178-181]. The hydrophosphination of phosphinoalkenes is believed to proceed through a mechanism analogous to that of hydroamination. The rate-determining alkene insertion into the Ln-P bond is nearly thermoneutral, while the faster protolytic o-bond metathesis step is exothermic (Fig. 22) [179,181]. The experimental observation of a first-order rate dependence on catalyst concentration and zero-order rate dependence on substrate concentration are supportive of this mechanism. A notable feature is a significant product inhibition observed after the first half-life of the reaction. This is apparently caused by a competitive binding of a cyclic phosphine to the metal center that impedes coordination of the phosphinoalkene substrate and, therefore, diminishes catalytic performance [179]. 

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... 

Stereochemical and kinetic analyses of the Brpnsted acid-catalysed intramolecular hydroamination/deuterioamination of the electronically non-activated cyclic alkene (13) with a neighbouring sulfonamide nucleophile have been found to proceed as an anh-addition (>90%) across the C=C bond to produce (15). No loss of the label was observed by and NMR (nuclear magnetic resonance) spectroscopies and mass spectrometry (MS). The reaction follows the second-order kinetic law rate = 2 [TfOH] [13] with the activation parameters being = 9.1 0.5 kcal moP and = -35 5 cal moP An inverse a-secondary kinetic isotope effect of d/ h = (1-15 0.03), observed for (13) deuteration at C(2), indicates a partial CN bond formation in the transition state (14). The results are consistent with a mechanism involving concerted, intermolecular proton transfer from an N-protonated sulfonamide to the alkenyl C(3) position coupled with an intramolecular anti-addition by the sulfonamide group. ... 

Hydroaminations occurring by nucleophilic attack on ir-ligands are the oldest class of hydroamination and are discussed first. A mechanism for the hydroamination of alk-enes and alkynes catalyzed by palladium(II) complexes is shown in Scheme 16.16. By this pathway, coordination of the alkene or alkyne through the -ir-system occurs to generate a cationic or electron-poor, neutral metal-olefin or metal-alkyne complex. Nucleophilic attack of the amine on the coordinated olefin or alkyne then occurs. Nucleophilic attack on coordinated olefins and alkynes is presented in detail in Chapter 11. As noted in Chapter 11, this nucleophilic attack occurs at the internal position of an alkene or alkyne. 

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. 

Examples of the [2+2] cycloadditions and the mechanisms of these processes were presented in detail in Chapter 13 on complexes containing metal-ligand multiple bonds. In short, coordination of the alkyne or allene precedes the [2+2] cycloaddition. This cycloaddition is thermodynamically favorable for aikynes and allenes, but is thermodynamically disfavorable for reactions of alkenes. Studies on the regioselectivity of the stoichiometric [2+2] cycloaddition and of the regioselectivity of zirconocene-catalyzed hydroamination revealed that the [2+2] process is reversible during the hydroaminations catalyzed by zir-conocene complexes. Moreover, it has been shown that addition of an alkyne to an isolated zirconocene azametallacyclobutene leads to exchange. 

The catalytic activity of 4 in intermolecular hydroamination of alkynes by anilines as well as in the intramolecular alkene and alkyne hydroamination has been reported [40]. The results show that in the presence of ]PhNMe2H+][B(CgF5) ], 4 could catalyze these reactions very efficiently (2.5 mol% catalyst, 20 - 80 °C). It was su ested that the Cp moiety was protonolyzed to give Cp H, which was identified by NMR. In most cases, excellent yields were achieved, indicating a possible high potential of Zn-Zn-bonded complexes for catalytic organic transformations. As the presumed mechanism is not discussed further, it is hitherto unclear whether a Zn species is prevalent in the catalytic cycle. 

For producing ri -coordinated allyl metal species, two pathways are proposed as shown in Scheme 4, and in either case an acid is involved, often added as a cocatalyst or in situ generated path (a) formation of metal hydride species followed by coordination of C-C double bond and subsequent migratory insertion into M-H bond [hydrometallation], and path (b) coordination of C-C double bond followed by protonation of the coordinated alkene [41]. To the terminal carbon of the rj -allyl system, an amine attacks from external side. This type of hydroamination has different characteristics in that the formation of C-H bond precedes by the formation of C-N bond, by contrast to the reactions of other mechanisms which have the opposite bond-forming order, that is, the formation of C-N bond occurs first. 

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