Alkene hydroamination catalysts

Figure 15.3 Croup 4 alkene hydroamination catalysts capable of hydroamination of established aminoalkene substrates.

In 2003, Livinghouse et al. also reported that chelating bis(thiophosphonic amidates) complexes of lanthanide metals, such as yttrium or neodymium, were able to catalyse intramolecular alkene hydroaminations. These complexes were prepared by attachment of the appropriate ligands to the metals by direct metalation with Ln[N(TMS)2]3- When applied to the cyclisation of 2-amino-5-hexene, these catalysts led to the formation of the corresponding pyrrolidine as a mixture of two diastereomers in almost quantitative yields and diastereos-electivities of up to 88% de (Scheme 10.81). 

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. 

New catalyst systems for intramolecular alkene hydroamination have also been developed Chem. Comm. 2004, 894 and Angew. Chem. lnt. Ed. 2004, 43, 5542). 

Previously reported bis(amidate)- and tethered-amidate-supported zirconium complexes can be used for alkene hydroamination catalysis, and all substrate scope and mechanistic investigations of these systems are consistent with the [2+2] cycloaddition mechanistic profile [61, 62). However, more recent catalyst systems that can be used with secondary amines show broader substrate scope, similar to that attained by rare earth elements and suggest a mechanistic similarity to that observed for previously intensely investigated rare earth hydroamination catalyst systems [7j. Such complexes are proposed to achieve ring closure via o-bond insertion, and thus, consideration of such a mechanistic profile in this case demanded further investigation. 

Key contributions in the development of late transition metal catalysts toward alkene hydroamination, which precede the 2008 comprehensive review [10], focus on contributions using group 9 and 10 metals. Preferred substrates for these transformations include aminoalkenes [230] for intramolecular reactivity or the use of activated alkenes such as styrene [93, 109, 113, 245] or alkenes substituted with electron-withdrawing substituents to generate hydroamination products via aza-Michael-type reactions [246-249]. Au has also been applied to the hydrofunctionalization of alkenes, although these reactions have demanded the use of protected amine substrates such as ureas [250], tosylamides [251], and carbamates [252]. 

Scheme 15.51 The Markovnikov selective intermolecular alkene hydroamination facilitated by Pd catalyst.

Late transition metals are particularly useful for enantioselective transformations with protected amines and in some cases arylamines however, simple alkylamines have rarely been addressed using these metal centers. Considering the mechanistic profiles for these reactions and the competitive coordination of amine and alkene with these systems, it would seem that late transition metals are preferred for less nucleophilic amines, while early transition metals and rare earth elements will be preferred for unprotected amines. As such, the development of hydroamination catalysts from different regions of the periodic table can result in complementary synthetic solutions. 

Several Au-ADC catalysts have been examined in intramolecular hydroamina-tion and hydroalkoxylation reactions of allenes, although no advantages over established systems were uncovered [27c,29a]. Notably, Hong and coworkers showed that highly bulky Au -ADC complex 32 and a comparably hindered acyclic aminooxycarbene complex provide catalytic activities comparable to those attained with equivalently bulky NHC-based catalyst 33 in a fairly challenging intramolecular alkene hydroamination reaction [15b,32]. By contrast, less bulky Au-ADC catalysts were ineffective. 

Watson DA, Chiu M, Bergman RG. Zirconium bis(amido) catalysts for asymmetric intramolecular alkene hydroamination. Organometallics 2006 25(20) 4731 733. 

Fig. 2.16 Copper-amido complexes as catalysts for the intermolecular hydroamination of electron-deficient alkenes...

The well-defined copper complexes 94 and 95 (Fig. 2.16) have been used as catalysts for the intermolecular hydroamination of electron-deficient alkenes [Michael acceptors, X=CN, C(=0)Me, C(=0)(0Me)] and vinyl arenes substituted... 

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. 

The first example of a heterogeneously catalyzed hydroamination of an alkene appeared in a 1929 patent in which it is claimed that NHj reacts with ethylene (450°C, 20 bar) over a reduced ammonium molybdate to give EtNH2 [24]. An intriguing reaction was also reported by Bersworth, who reacted oleic acid with NH3 in the presence of catalysts like palladium or platinum black or copper chromite to give the hydroamination product in quantitative yields [25]. However, this result could not be reproduced [26]. 

The hydroamination of alkenes has been performed in the presence of heterogeneous acidic catalysts such as zeolites, amorphous aluminosilicates, phosphates, mesoporous oxides, pillared interlayered clays (PILCs), amorphous oxides, acid-treated sheet silicates or NafioN-H resins. They can be used either under batch conditions or in continuous operation at high temperature (above 200°C) under high pressure (above 100 bar). 

Although zirconium bisamides Cp2Zr(NHAr)2 do not catalyze the hydroamination of alkenes (see above), they are catalyst precursors for the hydroamination of the more reactive double bond of allenes to give the anti-Markovnikov addition product (Eq. 4.96) [126]. 

Due to its marked atom economy, the intramolecular hydroamination of alkenes represents an attractive process for the catalytic synthesis of nitrogen-containing organic compounds. Moreover, the nitrogen heterocycles obtained by hydroamination/cyclisation processes are frequently found in numerous pharmacologically active products. The pioneering work in this area was reported by Marks et al. who have used lanthanocenes to perform hydroamination/cyclisation reactions in 1992. These reactions can be performed in an intermolecular fashion and transition metals are by far the more efficient catalysts for promotion of these transformations via activation of the... 

Hydroamination involves the addition of primary or secondary amines to alkenes to afford terminal or branched higher value substituted amines via anti-Markovnikoff or Markovnikoff addition.144 Although the addition of RNH2 to C=C is thermodynamically favorable (Equation (14)), there is a strong entropic factor disfavoring N-H addition which has to be overcome through use of a metal catalyst. 

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... 

If the more activated alkene 2-vinylpyridine is used in place of styrene with the same catalysts and the same range of substrates, anti-Markovnikoff hydroamination is also found. Thus, N-[2-(2 -pyridyl)ethyl]piperidine was isolated in 53% yield from reaction of 2-vinylpyridine with piperidine in the presence of [Rh(COD)2]+/2PPh3 under reflux. N H addition was observed with other amines, the remaining product in all cases being primarily that from oxidative amination (Table 12). When the catalytic reaction was run in the absence of phosphine, the yield of hydroamination product increased dramatically.171... 

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