Primary aminoalkenes cyclization

Scheme 11.15 Hydroamination/cyclization of primary aminoalkenes using a neutral bis (phosphinic amido) zirconium catalyst system [88].

Scheme n.17 Proposed mechanism for the hydroamination/cyclization of primary aminoalkenes involving group 4 metal imido species. 

Scheme 23 Cyclization of primary aminoalkenes can result in mixtures of hydroaminoalkylation and hydroamination products...

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. 

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]. 

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). 

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. 

Ytrium amido complexes generated in situ from chiral iV-benzyl-like-substituted binaphthyldiamines and [(THF)4Li][Y(CH2SiMe3]4 (both at 6-12 mol% loading) have been shown to catalyse the enantioselective intramolecular hydroamination of primary amines tethered to an alkene moiety (e.g. H2NCH2C(Me)2CH2CR=CR ) at 40-110 °C. Aminoalkenes bearing 1,2-dialkyl-substituted C=C bonds (R = H, R = Me) afforded the corresponding pyrrolidines with <77% ee, whereas trisubstituted alkenes (R = R = Me) were cyclized with only <55% eeP ... 

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... 

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