Olefin hydroaminomethylation

Many reactions can be conducted in tandem with hydroformylation, but the most extensively developed process is the combination of hydroformylation and reductive ami-nation. The combination of tttese reactions catalyzed by a single complex is called hydroaminomethylation and is shown in Equation 17.18. These reactions formally add tihe C-H bond of an aminomethyl group aaoss an olefin. Hydroaminomethylation reactions were discovered in the mid-twentieth century, but have been developed into more practical processes in recent years. These reactions rely on a complex that can simultaneously catalyze the hydroformylation of an aUcene and the reduction of an imine or enamine. 

The hydroformylation reaction strategy has recently been extended, in a novel way, to the manufacture of primary amines by hydroaminomethylation of olefins with ammonia in a two-phase system. Thus, 1-pentene was reacted with ammonia here hydroformylation to an aldehyde, with CO and H2, with subsequent reductive amination occurs in a domino reaction. The catalyst was Rh/Ir/TPPS (Zimmermann et al., 1999). 

Larock RC (1989) Comprehensive organic transformations. VCH, New York MobaUigh A, Seayad A, Jackstell R, Beller M (2003) Amines made easily a highly selective hydroaminomethylation of olefins. J Am Chem Soc 125 10311-10318... 

Abstract Aldehydes obtained from olefins under hydroformylation conditions can be converted to more complex reaction products in one-pot reaction sequences. These involve heterofunctionalization of aldehydes to form acetals, aminals, imines and enamines, including reduction products of the latter in an overall hydroaminomethylation. Furthermore, numerous conversions of oxo aldehydes with additional C.C-bond formation are conceivable such as aldol reactions, allylations, carbonyl olefinations, ene reactions and electrophilic aromatic substitutions, including Fischer indole syntheses. 

Secondary and tertiary amines can be obtained if the hydroformylation of olefins is conducted in the presence of primary and secondary amines under elevated hydrogen partial pressures. Here the rhodium catalyst is involved in both steps, the hydroformylation of an olefin as well as the hydrogenation of the imine or enamine resulting from a condensation of the oxo-aldehyde with the amine (Scheme 14). This combination of hydroformylation and reductive amination is also known as hydroaminomethylation and has been applied to the synthesis of various substrates of pharmaceutical interest [55-57] as well as to the synthesis of macrocycles [60-63] and dendrimers [64,65]. 

Hydroaminomethylation is a simple, efficient and atom-economic method to synthesize various amines. This one-pot reaction consists of three consecutive steps in the first step a hydroformylation of an olefin is performed followed by the reaction of the resulting aldehyde with a primary or secondary amine to give the corresponding enamine or imine. Lastly, this intermediate is hydrogenated to the desired secondary or tertiary amine (Fig. 11) [33-39]. In most cases rhodium salts or complexes are used as the homogeneous catalyst in the hydroaminomethylation. 

One may improve efficiency of an o-DPPB directed hydroformylation by incorporating this reaction into sequential transformations (domino reactions) [16]. The hydroformylation itself should be ideally suited for such a purpose, since this reaction provides under fairly mild reaction conditions access to the synthetically valuable aldehyde functionality. The aldehyde itself should be ideally suited to allow for further skeleton-constructing reactions. One type of sequential transformations employing the hydroformylation reaction as a key step is the hydroaminomethylation of olefins originally discovered by Reppe [17]. However, efficient control of diastereoselectivity in the course of this hydroaminomethylation reaction was unknown [18, 19]. 

Originally discovered by Reppe and co-workers, hydroaminomethylation of olefins has attracted attention as an economical, one-pot synthesis of amines. Alper and co-workers have demonstrated that zwitterionic rhodium complex [Rh (q -cyclooctadiene)(q -CgH5BPh3)-] 74 is an excellent catalyst for hydroaminomethylation of phenylalkenes 75 to afford the corresponding branched methylated amines 76 with high regioselectivity (Scheme 22) [42]. 

The hydroaminomethylation of 1-pentene and ammonia, with a Rh/Ir/TPPTS catalyst in an aqueous/organic two-phase system, was developed by BeUer et al. [14]. Under standard hydroformylation conditions (130°C, 12 MPa) amines could be isolated in 75% yield. By increasing the ammonia/olefin ratio and by using the extraction effect of the organic solvent as in Ref. [10], the selectivity for primary amines could reach more than 90%. This method could also be used for propene and 1-butene to give butylamine and pentylamine as main products. 

Aliphatic amines are among the most important bulk and fine chemicals in the chemical and pharmaceutical industry [12]. Hydroaminomethylation of olefins to amines presents an atom-economic, efficient and elegant synthetic pathway toward this class of compounds. In hydroaminomethylation a reaction sequence of hydroformylatioti of an olefin to an aldehyde with subsequent reductive amination proceeds in a domino reaction [Eq. (4)] [13]. 

Specific examples of the hydroaminomethylations of olefins with secondary amines are shown in Equations 17.19-17.21. Cyclic and acyclic secondary amines occur in high yield with linear-to-branched ratios exceeding 50 to 1 in most cases when catalyzed by the rhodium complex generated from [Rh(COD)JBF and xantphos. The reaction of pen-tene with piperidine is shown in Equation 17.19. These reactions are also compatible with alcohol (Equation 17.20) and acetal functional groups (Equation 17.21). 

Carbonylative hydroaminomethylation (hydroformylation-reductive amination) [109-115] has only been reported for mono-olefin reactants, as hydroformylation of dienes and allenes suffers from poor regioselectivity and over-hydroformylation ... 

Raoufmoghaddam S (2014) Recent advances in catalytic C-N bond formation a comparison of cascade hydroaminomethylation and reductive amination reactions with the corresponding hydroamidomethylation and reductive amidation reactions. Org Biomol Chem 12 7179-7193 Wu X-F, Fang X, Wu L, Jackstell R, Neumann H, Beller M (2014) Transition-metal-catalyzed carbonylation reactions of olefins and alkynes a personal account. Acc Chem Res 47 1041-1053... 

The same catalytic system mediates also the hydroaminomethylation of olefins (Scheme 1.39) [44]. Besides piperidine, several other cyclic and linear primary and secondary amines could be utilized. Terminal and internal olefins were equally suitable for the reaction. With enamines and enamides, respectively, 1,3-diamines were formed in moderate to good yields. 

Karakhanov and coworkers [41] incorporated hydroformylation with methyl-formate in a hydroaminomethylation tandem reaction by using a dual metal catalyst consisting of homogeneous Ru and Rh complexes (Scheme 3.19). In contrast to rhodium, the ruthenium catalyst was used in excess. The transformation is exemplified in the scheme with 1-pentene as substrate. Also, other terminal and internal olefins could be converted with dimethylamine into the corresponding amines. High temperatures enhanced the formation of the desired amines and lowered the degree of olefin hydrogenation. The reaction proceeded also well. 

Figure 5.10 Ligands for highly n-regioselective rhodium-catalyzed hydroaminomethylation of internal olefins.

The term hydroaminomethylation (HAM) describes the one-pot reaction of olefins with syngas, ammonia, and primary or secondary amines to afford secondary or tertiary amines with one carbon atom more than in the starting... 

Hydroaminomethylation of terminal as well as internal aliphatic and aromatic olefins with various amines in the presence of [Rh(COD)(Imes)Cl] as a catalyst was described (Imes = l,3-dimesitylimidazol-2-ylidene). Goodtoexcellentyieldsandhigh chemoselectivitieswereobtainedinTHFat85-105 CusingO.l mol%ofcatalyst]162],... 

Phenoxaphosphino-modified xantphos-type ligands in the rhodium-catalyzed hydroaminomethylation of internal olefins were found to give linear amines. Hydro-aminomethylation and each of its individual steps were monitored by high-pressure infrared spectroscopy. The results suggest that hydroaminomethylation takes place by a sequential isomerization/hydroformylation/amination/hydrogenation pathway [170]. 

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