Hydroaminomethylation of alkenes

Hydroaminomethylation of alkenes occurred to give both n- and /. so aliphatic amines catalyzed by [Rh(cod)Cl]2 and [Ir(cod)Cl]2 with TPPTS in aqueous NH3 with CO/H2 in an autoclave. The ratio of n-and /.soprimary amines ranged from 96 4 to 84 16.178 The catalytic hydroaminomethylation of long-chain alkenes with dimethylamine can be catalyzed by a water-soluble rhodium-phosphine complex, RhCl(CO) (Tppts)2 [TPPTS P(m-C6H4S03Na)3], in an aqueous-organic two-phase system in the presence of the cationic surfactant cetyltrimethy-lammonium bromide (CTAB) (Eq. 3.43). The addition of the cationic surfactant CTAB accelerated the reaction due to the micelle effect.179... 

Hydroaminomethylation of Alkenes (Domino Hydroformylation-Reductive Ami nation) 439... 

Crozet D, Urrutigoity M, Kalck P (2011) Recent advances in amine synthesis by catalytic hydroaminomethylation of alkenes. ChemCatChem 3(7) 1102-1118. doi 10.1002/ cctc.201000411... 

Aliphatic amines are amongst the most important bulk and fine chemicals in the chemical and pharmaceutical industry [13]. Hydroaminomethylation of alkenes to amines presents an atom-economic, efficient and elegant synthetic pathway towards this class of compounds. In hydroaminomethylation a reaction sequence of hydroformylation of an alkene to an aldehyde with subsequent reductive amina-tion proceeds in a domino reaction (see Eq. 4) [14]. Recently, the highly selective hydroamination of alkenes with ammonia to form linear primary and secondary aliphatic amines with a new Rh/Ir catalytic system (] Rh(cod)Cl 2], ] Ir(cod)Cl 2], aqueous TPPTS solution) has been described (see Scheme 2) [15]. The method is of particular importance for the production of industrially relevant, low molecular weight amines. 

Scheme 2 Selective hydroaminomethylation of alkenes catalyzed by a new Rh/lr system.

Hydroaminomethylation of alkenes [path (c)] wiU not be considered [12]. This review deals exclusively with the hydroamination 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 reaction of the N-H bond of amine derivatives such as carboxamides, tosylamides, ureas, etc. will not be considered. 

Given the previous discussion on reductive amination, it is surprising that the potentially more complicated domino hydroformylation-reductive amination reactions have been more thoroughly developed. The first example of hydroaminomethylation was reported as early as 1943 [83]. The most synthetically useful procedures utilize rhodium [84-87], ruthenium [88], or dual-metal (Rh/Ir) catalysts [87, 89, 90]. This area was reviewed extensively by one of the leading research groups in 1999 [91], and so is only briefly outlined here as the second step in the domino process is reductive amination of aldehydes. Eilbrachfs group have shown that linear selective hydroaminomethylation of 1,2-disubstituted alkenes... 

Scheme 15.13 Hydroaminomethylation of terminal alkenes to linear amines.

A more recent report thoroughly investigates hydroaminomethylation of terminal alkenes to give high yields of linear (linear branched=99 1) tertiary amines from secondary amines and terminal alkenes or linear secondary... 

In a similar manner, polymers with unsaturated chains or side chains can be converted to polyamines [66-69]. Conjugated diolefins usually undergo hydroformylation with low selectivities [70]. Mostly hydrogenation of at least one double bond occurs and mixtures of various saturated and unsaturated amines and diamines are obtained [71]. Similar to alkenes also alkynes may serve as unsaturated compounds in hydro aminomethylation reaction sequences. Although synthetically attractive, only a few investigations towards hydroformylation and hydroaminomethylation of alkynes in the presence of N-nuclcophilcs are known. Usually a preferred transformation to furanonic derivatives is observed under hydroformylation conditions [27]. 

A successful homogeneous system involves the catalytic hydroaminomethylation of internal alkenes to produce the linear products over an organometallic Rh complex which contains the rigid bulky diphosphorus ligandl . It helps to catalyze the combined sequence of bond isomerization, CO insertion and amination at the Rh center with stereochemical control. The unique feature of this catalyst is that all three of these different... 

The hydroaminomethylation of aUcenes was originally discovered by Reppe [94] and consists of the hydroformylation of an alkene, followed by reaction of... 

The improvements made in hydroaminomethylation technology suggest that certain variants of this reaction are sufficiently developed for the potential production of amines. The synthesis of linear tertiary and secondary amines from terminal alkenes shows promise in this regard. Belief s recent contributions towards hydroaminomethylation using ammonia to produce linear primary amines, which are of industrial significance due to their abundance, suggest a bright future for this reaction. Branched selective hydroaminomethylation remains relatively underdeveloped and needs further study. 

Scheme 16 Auto-tandem hydroaminomethylation reaction of a terminal alkene (e.g., formation of the linear product)...

Hydroaminomethylation reactions can be accomplished by addition of nucleophilic a-amino alkyl radicals (generated from amines) onto electron-deficient alkenes [7, 21], Amines have a low oxidation potential, and are easily oxidized by excited aromatic ketones bearing electron-donating substituents (e.g., Michler s ketone) or... 

This hydroaminomethylation has only been applied in homogeneous one-phase systems until now. The reaction will mostly lead to secondary and tertiary amines, because the intermediate primary amines will further react with the aldehyde formed to secondary amines. The synthesis of the technically important primary amines from ammonia and alkenes via hydroaminomethylation was investigated, but only low selectivities (32 %) and TOFs (9 h ) to primary amines could be achieved, despite the high excess of ammonia. Other side products, e. g., via aldo-lization, are also observed. 

The most important hydroaminomethylations for commodity chemicals woidd be hydroaminomethylations with ammonia, but this reaction remains a challenge. Hydroaminomethylation reactions have more often been conducted between alkenes and secondary aliphatic amines, and these reactions can be useful for fine-chemical s)mthesis. Intramolecular hydroaminomethylations can also be valuable, and many examples of intramolecular hydroaminomethylations to form nitrogen heterocycles have been reported. 

Hydroaminomethylation can be considered to be a sequence of two catalytic processes linked by an uncatalyzed process, as summarized in Scheme 17.16. First, catalytic hydroformylation of an alkene occurs by the steps described in the previous section on hydroformylation. This process is then followed by an uncatalyzed condensation of the amine with the aldehyde. When this reaction is conducted with a secondary amine, an enamine results and when the reaction is conducted with a primary amine, an imine results. This condensation process is then followed by hydrogenation of the resulting enamine or imiiie by the mechanisms described in Chapter 15, the chapter on hydrogenation. 

From an economical and environmental point of view, one pot synthesis of amines from alkenes is a superior pathway over conventional multistep pathways. Hydroaminomethylation is an attractive tool for the synthesis of amines and has been used in the pharmaceutical and chanical industries. Blum developed a heterogeneous system based on [Rh(cod)Cl]2 immobilized within a sol-gel matrix as a highly efficient, regioselective, and recyclable catalyst for hydroaminomethylation reaction of vinylarenes with aniline derivatives (anilines or nitrobenzenes) under mild conditions. 

Several synthetic approaches toward 3,3-diarylpropyl- or 4,4-diarylbutylamines (Figure 12.2) comprise hydroformylation as the key step. One possible route involves the reaction of the (D.co-diarylalkylhalide, obtained in a few steps from the hydroformylation product linear aldehyde, with an appropriate amine [19]. On the contrary, the aldehydes can be converted directly into the amines via a transition metal catalyzed reductive amination reaction [20]. Although these methods have heen employed efficiently for the synthesis of compounds 10,11 [19], and 12 [20], the most elegant solution is the direct hydroaminomethylation where the initial hydroformylation of the alkene is followed by the condensation of the intermediate aldehyde with the amine present in the reaction mixture and a final hydrogenation to give a saturated secondary or tertiary amine. 

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