Hydroamination of alkenes and alkynes

Organolanthanides catalyze the hydroamination of alkenes and alkynes, via the reaction sequence... 

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 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. 

Huang L, Arndt M, GooBen K, Heydt H, GooBen LJ (2015) Late transition metal-catalyzed hydroamination and hydroamidation. Chem Rev 115(7) 2596-2697 Pirnot MT, Wang Y-M, Buchwald SL (2016) Copper hydride-catalyzed hydroamination of alkenes and alkynes. Angew Chem Int Ed 55(l) 48-57... 

The hydroamination of alkenes and alkynes provides a highly atom-economical method for the preparation of substituted amines and imines. Despite substantial efforts and recent progress, the development of a generally applicable functional group-tolerant catalyst for this reaction remains a challenge, and intense research continues in this field. An interesting example has been reported by means of Rh combined with a bidentate NHC ligand [eqn (8.14)]. Complex 32 was found to catalyse the intramolecular hydroamination of aminoalkynes. However, the turnover rates remained modest with values up to 50 h ... 

Hydroaminomethylahon of alkenes [path (c)j wiU not be considered [12]. This review deals exclusively with the hydroaminahon reaction [path (d)], i.e. the direct addition of the N-H bond of NH3 or amines across unsaturated carbon-carbon bonds. It is devoted to the state of the art for the catalytic hydroamination of alkenes and styrenes but also of alkynes, 1,3-dienes and allenes, with no mention of activated substrates (such as Michael acceptors) for which the hydroamination occurs without catalysts. Similarly, the reachon of the N-H bond of amine derivatives such as carboxamides, tosylamides, ureas, etc. will not be considered. 

Organometallic complexes of the /-elements have been reported that will perform both intra-and intermolecular hydroamination reactions of alkenes and alkynes, although these lie outside of the scope of this review.149-155 Early transition metal catalysts are not very common, although a number of organometallic systems exist.156-158 In these and other cases, the intermediacy of a metal imido complex LnM=NR was proposed.159,160 Such a species has recently been isolated (53) and used as a direct catalyst precursor for N-H addition to alkynes and allenes (Scheme 35).161,162... 

The scope of hydroamination now includes many types of compounds containing N-H bonds and many types of alkenes and alkynes. Because the scope of these reactions is rapidly changing and many reviews of these processes have been published elsewhere, this section of the chapter provides a broad overview of the scope of these reactions. It then... 

Scheme 1 The catalytic hydroamination of alkenes (a), alkynes (b), allenes (c), and dienes (d) leads to amines, imines, and enamines. The reactirais may also be performed in an intramolecular fashion (not shown)...

Muller, T.E., Hultzsch, K.C., Yus, M., Foubelo, F., and Tada, M. (2008) Hydroamination direct addition of amines to alkenes and alkynes. Chemical Reviews, 108, 3795-3892 and references therein. 

Despite the industrial importance of amines and imines, hydroamination, i.e. the direct reaction of alkenes or alkynes with primary or secondary amines, is only used in one commercial process where isobutene and ammonia are converted in the presence of a zeolite catalyst to /-butylaminc. Turnover frequencies are generally very low and consequently, high catalyst loadings are necessary, which in turn demands efficient recycling. 

Reactions of intramolecular hydroamination of alkenes, alkynes, and allenes with the formation of A-heterocycles in the presence of lanthanocene catalysts 02CRV2161. 

The hydroamination of alkynes is a highly atom-efficient approach to the synthesis of enamines and imines, as well as to the synthesis of A-heterocyclic compounds such as indoles and pyrroles, which are widely occurring functional groups in biologically active molecules. Also included in this section is the hydroamination of allenes and alkenes, as the reaction of these substrates with chiral bimetallic catalysts has been shown to yield the chiral amine products with high enantioselectivity. 

Amidate and amidinate complexes of early metals are also known. In these complexes, the TT-bonding interaction is reduced because of the adjacent ir-system. These ligands may bind in a k - or K -fashion, or they can bind in an ir)Mashion with the metal interacting with the entire ir-system of the amidate, as shown in Figure 4.3. The synthetic routes used to prepare these complexes are similar to those used to prepare early-metal-amido complexes. The reactivity of these ligands is limited—most often they serve as ancillary ligands that modulate the steric and electronic properties of the central metal. As such, amidate complexes have been employed as catalysts for the hydroamination of terminal alkenes - and alkynes that is described in Chapter 14. 

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. 

Neutral group 4 metal complexes appear to possess a relatively broad scope for catalytic hydroaminations. They have been employed for the intramolecular as well as the intermolecular hydroaminations of alkenes, alkynes, and allenes. Catalytic hydroaminations (and hydrohydrazinations) of alkynes have been exploited as key steps in catalytic multicomponent reactions, giving rise to highly functionalized substrates, in particular to several types of N-heterocycles. Chapter 13 by Gade focuses, inter alia, on two case histories involving hydrohydrazinations which exemplify key challenges and the way they may be addressed in practice. 

In the hydroamination of unsaturated carbon-carbon bonds, gold catalysts play an important role. Intermolecular hydroamination of alkenes [177], 1,3-dienes [204], terminal and internal alkynes [205], and allenes [206] are known to proceed smoothly in the presence of PhsP AufI) or AuCls catalyst. In addition, amino olefins also efficiently undergo intramolecular hydroamination using similar gold catalysts. He and coworkers have developed the catalytic cycloaddition of tosylated amino olefins [207], A representative example is shown in Scheme 18.35. When N-tosylated y-amino olefin (97) is exposed to a mixture of PhsP AuCl and AgOTf (5 mol% each) in toluene at 85 °C, pyrrolidine (98) is obtained in 96% yield. The gold(I)-catalyzed intramolecular hydroamination is applicable to N-alkenyl carbamates [208], N-alkenyl carboxamides [209], and N-alkenyl ureas [210], The use of microwave irradiation results in completing the hydroamination in a much shorter time than that required under thermal reaction conditions [211], The... 

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. 

Alkene hydroamination has been known for many years, but has been little used as a method in organic synthesis. Tobin Marks of Northwestern recently published a series of three papers that will make this transformation much mote readily accessible. In the first (J. Am. Chem. Soc. 125 12584,2003) he describes the use of a family of lanthanide-derived catalysts for intermolecular hydroamination of alkynes (to make imines, not illustrated) and alkenes. With aliphatic amines, the branched (Markownikov) product is observed, 1 — 2. With styrenes, the linear product is formed. When two alkenes are present, the reaction can proceed (3 —> 4) to form a ring, with impressive regioselectivity. 

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