Hydroamination catalysts

A range of rhodium complexes have been studied as hydroamination catalysts. Treatment of norbornene with a mixture of aniline and lithium anilide in the presence of [Rh(PEt3)2Cl]2 at 70 °C for over 1 week yields the exo addition product in ca. 15% yield.165... 

An investigation comparing different hydroamination catalysts for the conversion of enamine alkynes to pyrroles is illustrated in Scheme 12.26 46 In this test, different... 

Aillaud, I., Lyubov, D., Collin, J. et al. (2008) Chiral amido alkyl rare earth complexes a new family of asymmetric intramolecular hydroamination catalysts. Organometallics, 27, 5929. 

Fig. 15 Constrained-geometry rare-earth metal hydroamination catalysts [118,119]...

Fig. 17 Chelating diamines used as ligands for nonmetallocene hydroamination catalysts...

In the same year, the first structurally defined biaryl diamide complexes as enantioselective intramolecular hydroamination catalysts were reported by Schulz and coworkers. They are the first example of lanthanide catalysts supported by a binaphthyl diamide ligand. 2 equiv of the lithium salt of the binaphthyl diamide ligand Li2L41 and anhydrous LnCls in THF at ambient temperature generated ate complexes [Li(THF)4][Ln(L41)2] (Ln = Sm 197 and Yb 198) via salt elimination (Scheme 76). 

The ate complexes [Li(THF)4][Ln (R) 1,1 CioH6N(R) 2 2] (R) 32 Ln = Sm, Yb, Y R = alkyl) [53 57, 60] are unusual hydroamination catalysts as they lack an obvious leaving amido or alkyl group that is replaced during the initiation step by the substrate. It is very likely that at least one of the amido groups is protonated during the catalytic cyde, analogous to the mechanism proposed for Michael additions and aldol reactions catalyzed by rare earth metal alkali metal BINOL heterobime tallic complexes [69, 70]. The observation of similar selectivities for rare earth metal... 

While hydroamination catalysts based on transition metals have been studied intensively over the past two decades, only a limited number of reports on alkali metal based hydroamination catalysts have emerged, although the first reports date back 60 years [71]. In particular, the application of chiral alkali metal complexes in asymmetric hydroamination of nonactivated aminoalkenes has drawn little attention to date [72, 73]. Also, attempts to perform asymmetric hydroamination utilizing... 

Palladium-based catalysts for enantioselective hydroamination reactions were discovered by extending the results of a high-throughput screening approach directed toward the discovery of non-selective hydroamination catalysts, reported by the Hartwig group in 2001. The approach taken by Hartwig and co-workers is described in Section 1.13.2.5. ... 

Early transition metals, groups 3, 4, and 5, are some of the first reported and mechanistically explored hydroamination catalysts [7, 8, 20, 21). In particular. 

Allene hydroamination is less commonly explored, even though the thermodynamic profile of the reaction is comparable to alkyne hydroamination [40]. Intermolecular allene hydroamination has been established using group 4 catalysts in combination with reactive arylamine substrates [8, 41]. The more reactive aforementioned alkyne hydroamination catalyst 7 has been shown to be usefiil for allene hydroamination catalysis in an intermolecular manner, even with less reactive, sterically less demanding alkylallene substrates. In this case, only the branched product is observed (Table 15.5). These results show good selectivity for the branched product, and recent results show that even heteroatom-substituted allenes can be tolerated with this precatalyst [42]. 

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

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. 

Alkyne hydroamination has been extensively reviewed [3, 4, 10] and important contributions using late transition metals have been realized to give the Markovnikov-type products most typically. Interestingly, in 2007, Fukumoto reported a tris(pyrazolyl borate)rhodium(l) complex for the anti-Markovnikov hydroamination of terminal aUcynes with both primary and secondary amine substrates, although yields with primary amines are always reduced compared to those with secondary amines (Scheme 15.26). Desirable functional group tolerance is also noteworthy for this regioselective hydroamination catalyst [187]. 

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. 

More recent contributions take advantage of hydroamination disconnection strategies in the assembly of more comphcated natural products. In these examples, simple hydroamination was not required, but an exploration of known hydroamination catalyst systems resulted in the identification of suitable reaction conditions for catalytic hydroguanidination reactions for the assembly of complex alkaloid targets. 

Reaction conditions Ethanol-dichloroethane, room temperamre Synthetic strategy One-step hydroamination Catalyst Au(I)Cl(PPh3)/AgNTf2... 

Furthermore, this follow-up study also illustrated the broad applicability of DMCs for the hydroamination of various substrate molecules [37]. Zn-Co-DMCs could catalyze the hydroamination reaction of both aromatic and aliphatic alkynes with aromatic as well as aliphatic amines, a rare trait in heterogeneous hydroamination catalysts. 

---