Lanthanide-catalyzed hydroamination

The scope of the lanthanide-mediated, intramolecular amination/cyclization reaction has been determined for the formation of substituted quinolizidines, indolizidines, and pyrrolizidines,1046 as well as tricyclic and tetracyclic aromatic nitrogen heterocycles.1047 The amide derivative OT ro-[ethylene-bis(indenyl)]ytterbium(m) bis(trimethyl-silyl)amide catalyzes the hydroamination of primary olefins in excellent yields.701 A facile intramolecular hydroamination process catalyzed by [(C5H4SiMe3)2Nd(/r-Me)]2 has also been reported. The lanthanide-catalyzed hydroamination enables a rapid access to 10,1 l-dihydro-5//-dibenzo[tf,rf]cyclohepten-5,10-imines (Scheme 283).1048... 

Arredondo VM, Tian S, McDonald FE, Marks TJ. Organo-lanthanide-catalyzed hydroamination/cyclization. efficient aUene-based transformations for the syntheses of naturally occurring alkaloids. J. Am. Chem. Soc. 1999 121(15) 3633-3639. 

When Marks and co-workers [10] published their investigations of the organo-lanthanide-catalyzed intramolecular hydroamination of appropriate a,ai-amino-lefms, the opened a useful synthetic route to different types of cyclic amines (Scheme 4) in combination with a thorough analysis of the catalytic reaction mechanism and the structure-reactivity relationships. 

Organo-/-element-catalyzed hydroaminations have been extensively investigated for more than 10 years.1034-1038 Lanthanide metallocenes catalyze the regiospecific intermolecular addition of primary amines to acetylenic, olefinic, and diene substrates at rates which are —1/1000 those of the most rapid intramolecular analogs. Kinetic and mechanistic data argue for turnover-limiting C=C/C=C insertion into an Ln-N bond, followed by protonolysis of... 

Some of the most active catalysts for the hydroamination of alkynes are based on lanthanides and actinides. The turnover frequencies for the additions are higher than those for lanthanide-catalyzed additions to alkenes by one or two orders of magnitude. Thus, intermolecular addition occurs with acceptable rates. Examples of both intermolecular and intramolecular reactions have been reported (Equations 16.87 and 16.88). Tandem processes initiated by hydroamination have also been reported. As shown in Equation 16.89, intramolecular hydroamination of an alk5me, followed by cyclization with the remaining olefin, generates a pyrrolizidine skeleton. Hydroaminations of aminoalkynes have also been conducted with the metallocenes of the actinides uranium and thorium. - These hydroaminations catalyzed by lanthanide and actinide complexes occur by insertion of the alkyne into a metal-amido intermediate. 

The hydroamination of alkenes and alkynes has been of longstanding interest in organometallic chemistry [26]. Much of the early work in this area focused on early transition metal or lanthanide metal catalyst systems. However, much recent progress has been made in late-metal catalyzed hydroamination chemistry, and several interesting hydroamination reactions that afford nitrogen heterocycles have been developed using palladium catalysts. 

Reznichenko A, Hultzsch K (2012) Early transition metal (group 3-5, lanthanides and actinides) and main group metal (group 1, 2, and 13) catalyzed hydroamination. Top Organomet Chem. doi 10.1007/3418 2011 22... 

Early Transition Metal (Group 3-5, Lanthanides and Actinides) and Main Group Metal (Group 1, 2, and 13) Catalyzed Hydroamination... 

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. 

Intramolecular addition of amine N-H bonds to carbon-carbon multiple bonds would afford nitrogen heterocycles. To realize catalytic cyclization of a,co-aminoalkenes or aminoalkynes, various catalytic systems have been developed especially with early transition metals such as titanium, zirconium, lanthanide metals, and actinide metals [ 12], Late-transition-metal catalysis based on Ni, Pd, and Rh has also proved to be efficient [ 12], Recently, the ruthenium-catalyzed intramolecular hydroamination of aminoalkynes 15 was reported to afford 5-7-membered ring products 16 in various yields (Eq. 6) [13]. Among... 

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. 

To catalyze the direct hydroamination of olefins according to eq. (1) two basic approaches have been employed involving primarily the activation either of the amine or of the olefin. One possible way to activate the amine for catalysis is the transformation to the much stronger nucleophilic amide ion by deprotonation. Thus, the amides of strongly electropositive metals, such as alkali metals, alkaline earth metals, or lanthanides, are able to react with the C-C double bond under... 

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]... 

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... 

Intermolecular additions of primary amines to alkenes have also been reported using lanthanide catalysts. These reactions, although slow, do occur to high conversion. Similar to hydroaminations catalyzed by late transition metal complexes, these reactions form the products from Markovnikov addition of the N-H bond across the olefin. One example of such a reaction is shown in Equation 16.59. ... 

The bulk of the studies on intramolecular hydroamination of alkenes catalyzed by lanthanide complexes have been conducted using lanthanocene complexes or half-sandwich lanthanide complexes. The prototypical cyclizations of aminoalkenes to form five- and six-membered rings are shown in Equation 16.61. These reactions occur with exclusive Markovnikov selectivity. These reactions have also been conducted using arylamines, as shown in Equation 16.62. The intramolecular reactions of amines catalyzed by certain lanthanide complexes occur with 1,1- and 1,2-disubstituted olefins (Equation 16.63), although such reactions require high temperatures. 

These intramolecular hydroaminations lead to the formation of chiral products. Thus, several studies have been devoted to developing ligands for enantioselective, intramolecular hydroaminations of olefins catalyzed by lanthanide complexes. ° Selectivities of these reactions with chiral cyclopentadienyl derivatives have been modest. Selectivities have been higher with catalysts containing non-cyclopentadienyl ligands. Some of tlie most selective catalysts are the yttrium complexes of the bis(thiolate) ligands reported by Livinghouse, the scandium and lutetium complexes of 33 -disubstituted binaphtholates reported by Hultzsch, and the BINAM-based bisamidates of Schafer.- A representative cyclization catalyzed by a member of each of these classes of catalyst are shown in Equation 16.64. 

Catalysts for tfie additions of amines to vinylarenes have also been developed. These catalytic reactions include some of the first hydroaminations of unstrained olefins catalyzed by late transition metals, as well as examples catalyzed by lanthanide complexes. These additions occur with Markovrukov selectivity with one set of catalysts and with anti-Markovnikov selectivity with several others. These additions occur by several different mechanisms that are presented in Section 16.5.3.2. 

Lanthanide complexes also catalyze the hydroamination of 13-dienes. The lanthanide catalysts originally developed for the intramolecular hydroamination of aminoalkenes are particularly active for the intramolecular additions of alkyl amines to dienes. The scope of this process is broad an illustrative example showing the high diastereoselectiv-ity of the cyclization of a chiral amine is shown in Equation 16.82. These reactions occur by insertion of the diene into a lanthanide-amide intermediate to form an allyl-metal intermediate. 

Hydroamination of Alkynes Catalyzed by Lanthanide and Actinide Complexes... 

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. 

The hydroamination of olefins has been shown to occur by the sequence of oxidative addition, migratory insertion, and reductive elimination in only one case. Because amines are nucleophilic, pathways are available for the additions of amines to olefins and alkynes that are unavailable for the additions of HCN, silanes, and boranes. For example, hydroaminations catalyzed by late transition metals are thought to occur in many cases by nucleophilic attack on coordinated alkenes and alkynes or by nucleophilic attack on ir-allyl, iT-benzyl, or TT-arene complexes. Hydroaminations catalyzed by lanthanide and actinide complexes occur by insertion of an olefin into a metal-amide bond. Finally, hydroamination catalyzed by dP group 4 metals have been shown to occur through imido complexes. In this case, a [2+2] cycloaddition forms the C-N bond, and protonolysis of the resulting metallacycle releases the organic product. 

Hydroamination of alkenes can be catalyzed by lanthanide alkyls via insertion, as shown in Eq. 14.79. ... 

Metal-catalyzed asymmetric hydroamination/cyclization reaction (for Lanthanide complexes) is believed to proceed through catalytic pathways as shown by Marks and co-workers. It is speculated that metal amide complex A is the starting point of the catalytic cycle (Scheme 39.2). 

Riegert D, Collin J, Meddour A, Schulz E, Trifonov A. Enantioselective intramolecular hydroamination catalyzed by lanthanide ate complexes coordinated by A-substituted (R)-l,l -binaphthyl-2,2 -diamido ligands. J. Org. Chem. 2006 71(6) 2514-2517. 

Many transition metals and lanthanide-based complexes have been shown to catalyze (5.7.2)-type hydroamination reactions. In many cases the catalysts based on lanthanides are found to have significant activity. Structures 5.70 and 5.71 are two typical examples of transition metaland lanthanide-based precatalysts. 

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