Chiral aminoalkenes

Catalyst systems obtained in situ from rare-earth metal trisamides Ln N-(SiMc3)2 3 and various chelating diamines (Fig. 17) have shown good activity in the cyclization of aminoalkenes (Schemes 3 and 4) [123,125-127]. The more challenging cyclization of the chiral aminoalkene 26 can be accomplished with... 

The binaphtholate complexes (R)-33 were successfully applied in the efficient kinetic resolution of chiral aminoalkenes (Table 5) [101,163,171]. Racemic aminopentenes can be kinetically resolved with resolution factors / as high as 19. The resolution factor value depends dramatically on the nature of the substituent R. Mechanistic studies have revealed that diminished efficiencies in the kinetic resolution of aminoalkenes with aliphatic substituents is caused by an unfavorable state of the Curtin-Hammett pre-equilibrium that favors the mismatching substrate-catalyst complex, whereas in the significantly more efficient kinetic resolutions of aryl-substituted aminoalkenes the matching substrate-catalyst complex predominates the pre-equilibrium [171]. 

The diastereoselective cyclization of chiral aminoalkenes, such as a substituted hex... 

Organolithium mediated cycloisomerization of chiral aminoalkenes may proceed with high diastereoselectivities when favored by the substrate geometry. The last step ofthe enantioselective synthesis of ( ) codeine (80), reported by Trost and Tang [121], consisted of an intramolecular hydroamination. Treatment of amine 79 with LDA or wBuLi in refluxing THF left the starting material unreacted. However, irradiation of the amine/LDA solution with a 150 W tungsten lamp led to diastereoselective cycloisomerization to form ( ) codeine (80) (Eq. 11.11). 

The efficient kinetic resolution of chiral aminoalkenes has been achieved utilizing the binaphtholate complexes (R) 38 Ln (Table 11.3) [52, 124]. Various chiral amino pentenes were kinetically resolved with resolution factors/(defined as f= x fefast/fesiow, where is the Curtin Hammett equilibrium constant between the two diastereomeric substrate/catalyst complexes and kfast/fesiow being the ratio between the faster and the slower reaction rate constant) as high as 19 and enantiomeric excess for recovered starting material reaching >80% ee at conversions dose to 50%. The... 

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. 

The binaphtholate complexes (R)-63 were successfully applied in the efficient kinetic resolution of chiral aminoalkenes (Table 16) [67, 121, 122]. Racemic... 

A dimeric proline-derived diamidobinaphthyl dilithium salt has been introduced as the first example of a chiral main group metal-based catalyst for asymmetric hydroami-nation-cyclization reactions of aminoalkenes.256... 

Scheme 11.10 Catalytic hydroamination/cyclization of aminoalkenes using chiral amino thiophenolate yttrium complexes [61].

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... 

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...

Attempts to utilise a chiral ligand scaffold to enhance the enantioselectivity of bimetallic Zn complexes have also been explored [112]. The efficiency of the bimetallic complex 72, which contains a (A,A)-1,2-diphenylethane scaffold bridging the two aUcyl zinc centres, as a catalyst for the intramolecular hydroamination of aminoalkenes was investigated (Scheme 27). Unfortunately, very poor enantioselectivity (<10% ee) was obtained for this reaction. Unrestricted rotation about the C-C bond of the ethane scaffold could lead to a large separation between the two Zn atoms, decreasing the potential for both metals to interact with the substrate. The vigorous reaction conditions (120°C) would also decrease discrimination between similar diastereomeric intermediates. 

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 ... 

Lanthanide complexes also catalyze the hydroamination of 13-dienes. The lanthanide catalysts originally developed for the intramolecular hydroamination of aminoalkenes are particularly active for the intramolecular additions of alkyl amines to dienes. The scope of this process is broad an illustrative example showing the high diastereoselectiv-ity of the cyclization of a chiral amine is shown in Equation 16.82. These reactions occur by insertion of the diene into a lanthanide-amide intermediate to form an allyl-metal intermediate. 

Chiral binaphtholate yttrium aryl complexes were highly active and enantiose-lective catalysts for asymmetric hydroamination of aminoalkenes as well as kinetic... 

The proUne-derived diamidobinaphthyl dilithium salt S,S,S)-66, which is dimeric in the sohd state and can be prepared via deprotonation of the corresponding tetraamine with n-BuLi, represents the first example of a chiral main-group-metal-based catalyst for asymmetric intramolecular hydroamination reactions of aminoalkenes [241], The unique reactivity of (S,S,S)-66, (Fig. 17) which allowed reactions at or below ambient temperatures with product enantioselec-tivities of up to 85% ee (Table 17) [241, 243] is believed to derive from the close proximity of the two lithium centers chelated by the proline-derived substituents. More simple chiral lithium amides required significantly higher reaction temperatures and gave inferior selectivities. 

Fig. 17 Chiral lithium-based catalysts for asymmetric hydroaminations of aminoalkenes [135, 241]...

Similar to alkali metals, only few chiral alkaline earth metal complexes have been apphed in asymmetric hydroaminations of nonactivated aminoalkenes [155, 244—248] and one of the greatest challenges has been the development of a chiral catalyst system that can resist facile ligand redistribution processes leading to achiral catalytically active species. Therefore, it is not too surprising that many systems are plagued with low enantioselectivities (Fig. 18, Table 18). 

---