Secondary aminoalkenes

Platinum-catalysed intramolecular hydroamination of unactivated alkenes with secondary alkylamines has been reported. Thus, a number of y- and 5-aminoalkenes reacted in the presence of a catalytic 1 2 mixture of [PtCl2(H2C=CH2)]2 (2.5 mol%) and PPh3 in dioxane at 120 °C for 16 h to form the corresponding pyrrolidine derivatives in moderate to good yields. The reaction displayed excellent functional group compatibility and low moisture sensitivity.92... 

The phenylselenenyl chloride induced intramolecular ring closure of ro-aminoalkenes can be utilized in the synthesis of nitrogen heterocycles. Olefinic primary amines do not cyclize readily in this reaction, while urethane derivatives and secondary amines cyclize according to the following scheme55 56. 

Tire first chiral group 4 metal catalyst system for asymmetric hydroamination/ cyclization of aminoalkenes was based on the cationic aminophenolate complex (S) 45 [85[. Secondary aminoalkenes reacted readily to yield hydroamination products with enantioselectivities of up to 82% ee (Scheme 11.14). For catalyst solubility reasons, reactions were commonly performed at 100 °G in bromobenzene using... 

Scheme 11.14 Hydroamination/cyclization of secondary aminoalkenes using a cationic chiral...

An interesting observation in these investigations is the fact that intermolecular hydroaminoalkylation catalysts are not viable for application in intramolecular reactions. Furthermore, there are no catalysts that are effective for the intramolecular hydroaminoalkylation of secondary aminoalkenes and all high yielding examples of intramolecular hydroaminoalkylation are restricted to primary aminoalkenes. Meanwhile, intermolecular hydroaminoalkylation with primary amines has not yet been reported. 

Few examples of intramolecular additions of amines to alkenes catalyzed by late transition metals have been published more examples of the additions of amides, carbamates, and tosylamides to alkenes catalyzed by this type of complex have been reported. Addition of a secondary amine across a tethered olefin catalyzed by a simple platinum-halide complex is shown in Equation 16.65a. A more recent catalyst based on [Rh(COD)JBF and a biaryldialkylphosphine leads to cyclizations of aminoalkenes with greater scope (Equation 16.65b). These reactions occur to form five- and six-membered rings, with or without groups that bias the system toward cyclization. They also occur with both internal and terminal olefins and with both primary and secondary amines. 

Scheme 15.8 Unsaturated side product observed during hydroamination of secondary aminoalkene.

Table 15 Zirconium-catalyzed hydroamination of secondary aminoalkenes.

Scheme 15.11 Proposed catalytic cycle for catalyst 5, capable of cyclizing secondary aminoalkene substrates.

Table 15.22 Rh-catalyzed intramolecular hydroamination of primary and secondary aminoalkenes.

Hollis [266] has directly compared Rh-and Ir-CCC-NHCpincer complexes (54) for application in cyclohydroamination of secondary aminoalkenes (Scheme 15.65). The Ir complex (54a) yielded slightly improved results, although high reaction temperatures (110 °C) and substrate scope limitations (for example, neither of these catalysts can mediate hydroamination with primary aminoalkenes and substituents... 

By modifying the auxiliary ligand to o-aminated salicylaldimine derivatives (Figure 15.9), dinuclear Zn complexes are obtained. These novel systems can effect hydroamination at room temperature with a variety of heteroatom-functionalized secondary aminoalkene substrates [278]. 

Remarkably, the commerdally available ZnEt2 in combination with the aforementioned anilinium BF4 salts result in systems that can catalyze secondary aminoalkene hydroamination at room temperature (Scheme 15.71) [279]. Not surprisingly, this same system can mediate the cyclohydroamination of aminoatkynes [279]. The nature of the salt cocatalyst was critical, pointing toward acid and counterion effects. While catalysis is stated to occur with primary aminoalkenes, only secondary aminoalkenes are reported with yields. Many of these substrates contain heteroatom functionality. Impressively, although slow, this catalyst system can achieve the cyclization of an unsubstituted aminoalkene (Scheme 15.72). 

Neutral group 4 metal complexes appear to possess a relatively broad scope for catalytic hydroaminations. They have been employed for the intramolecular hydroamination of alkynes [2], allenes [3], and alkenes [4] as well as the inter-molecular hydroaminations of alkynes [5] and allenes [6]. Primary aryl- and alkylamines readily react, but secondary amines have posed a greater challenge for this type of transformation with neutral catalysts [7]. For the reactions of the latter, cationic Zr and Ti complexes have been employed in intramolecular cyclizations of aminoalkenes [8]. Very recent work suggests that substrates that are difficult to hydroaminate may favor hydroaminoalkylations instead (Scheme 13.2) [9]. 

It should be noted that cationic titanium and zirconium catalysts, which are isoelectronic to neutral group 3 metal complexes, cyclize only aminoalkenes with a secondary amino group, whereas primary amines are urueactive [61, 62]. It has been proposed that the lanthanide-like insertion mechanism is operating in these systems, which is in agreement with DFT calculations [63]. 

Only a limited number of organoactinide catalysts have been investigated for the hydroamination/cyclization of aminoalkenes (Fig. 4, Table 2) [55, 96-98]. The constrained geometry catalysts 11-An (An = Th, U) show high activity comparable to the corresponding rare earth metal complexes and can be applied for a broad range of substrates [55, 96, 97]. The ferrocene-diamido uranium complex 12 was also catalytically active for aminoalkene cyclization, but at a somewhat reduced rate [98]. Mechanistic studies suggest that the actinide-catalyzed reaction occurs via a lanthanide-like metal-amido insertion mechanism and not via an imido mechanism (as proposed for alkyne hydroaminations), because also secondary aminoalkenes can be cyclized [55, 98]. 

Calcium and magnesium p-diketiminates were shown to catalyze hydroamination/ cyclization of terminal primary and secondary aminoalkenes with reasonable reactivity (Table 4, entries 1-5) [36, 39, 107]. While the reactivity of calcium species... 

Diastereoselective cycUzations of chiral aminoalkenes were also achieved for zirconium catalysts (Table 6). Interestingly, the cyclization of primary aminoalkenes gave predominately tran -disubstituted pyrrolidines in accordance to observations for rare earth metal-based hydroamination catalysts [17, 67, 74, 80-82,99,121,122], while the c -diastereomer was favored in case of the secondary aminoalkene. Plausible transition states are shown in Fig. 9. The chair-like transition state leading to the traws-isomer of the primary aminoalkene is less encumbered due to reduced 1,3-diaxial interactions, whereas gauche interactions of the (V-substituent make the c -pyrrolidine the preferred product in case of secondary aminoalkenes. 

Aminoalkenes with secondary amino groups generally cyclize slower and commonly also with diminished enantioselectivity in comparison to substrates with primary amino groups, presumably as a result of steric interference of the A7-alkyl substituent in the stereodetermining cyclization transition state (Table 15). The diamidobinaphthyl complex (/ )-60 and related complexes seem to be an exception [240], as they tend to provide slightly higher enantioselectivities (up to 83% ee) and faster reaction rates for secondary aminoalkenes in comparison to the corresponding primary aminoalkenes (compare Tables 14 and 15). 

Table 15 Asymmetric intramolecular hydroamination of aminoalkenes with a secondary amino group using post-metallocene rare earth metal catalysts...

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