Search

International audience; Chiral amines can be synthesized with high yields and enantioselectivities from abundant organic substrates using transition metal catalytic systems containing most of the time an appropriate chiral bidentate ligand. Reductive amination starts from ketones, hydroamination from alkenes, or alkynes in an inter- or intramolecular mode. In the hydroaminoalkylation reaction, a C–H function in α-position with regard to the nitrogen is activated and forms a new C–C bond. In the hydroaminomethylation, a one-pot carbonylation reaction, the olefin reacts with CO/H2 and amine. Complexes chiral-only-at-metal begin to be efficient to perform the photocatalytic chiral amination under mild conditions. Many recent trends are focused onto first-line transition metals. The major difficulties lie in the synthesis of chiral ligands and the design of a suitable coordination sphere.

The kinetic resolution of α‐substituted aminopentenes via intramolecular hydroamination was investigated using various 3,3′‐silyl‐substituted binaphtholate yttrium catalysts. High efficiencies in the kinetic resolution were observed for methyl‐, benzyl‐, and phenyl‐substituted substrates utilizing the cyclohexyldiphenylsilyl‐substituted catalyst 2c with resolution factors reaching as high as 90(5) for hex‐5‐en‐2‐amine (3a). Kinetic analysis of the enantioenriched substrates with the matching and mismatching catalyst revealed that the efficiency of catalyst 2c benefits significantly from a favorable Curtin–Hammett pre‐equilibrium and by a large kfast/kslow ratio. Other binaphtholate catalysts were less efficient due to a less favorable Curtin–Hammett pre‐equilibrium, which often favored the mismatching substrate‐catalyst combination. Cyclization of the matched substrate proceeds generally with large trans‐selectivity, whereas the trans/cis‐ratio for mismatched substrates is significantly diminished, favoring the cis‐cyclization product isomer in some instances.

N-heterocyclic carbene (NHC) ligands with naphthyl side chains were employed for the synthesis of unsaturated, yet isolable [(NHC)Ir(cod)](+) (cod=1,5-cyclooctadiene) complexes. These compounds are stabilised by an interaction of the aromatic wingtip that leads to a sideways tilt of the NHC-Ir bond. Detailed studies show how the tilting of such N-heterocyclic carbenes affects the electronic shielding properties of the carbene carbon atom and how this is reflected by significant upfield shifts in the (13) C NMR signals. When employed in the intramolecular hydroamination, these [(NHC)Ir(cod)](+) species show very high catalytic activity under mild reaction conditions. An enantiopure version of the catalyst system produces pyrrolidines with excellent enantioselectivities.

Stereoselective hydroaminations of unactivated alkenes are rare as this represents a very challenging synthetic transformation. The most efficient examples occur in biased intramolecular systems and highly enantioselective intermolecular examples are rare, which is consistent with the forcing conditions required to catalyze the reactions. This limited reactivity also accounts for the lack of highly diastereoselective hydroamination variants. Recently our group has shown that intermolecular Cope-Type hydroamination of unactivated alkenes can be achieved using simple aldehydes as catalysts. The aldehyde promotes pre-association of the two reaction partners, inducing temporary intramolecularity resulting in a remarkably facile hydroamination event. This thesis will present the development of two reactions: intermolecular enantioselective Cope-type hydroamination and intermolecular diastereoselective Cope-type hydroamination of allylic amines.

A new neutral tridentate 1,4,6-trimethyl-6-pyrrolidin-1-yl-1,4-diazepane (L) was prepared. Reacting L with trialkyls M(CH(2)SiMC(3))(3)(THF)(2) (M = Sc, Y) and tribenzyls M(CH(2)Ph)(3)(THF)(3) (M = Sc, La) yielded trialkyl complexes (L)M(CH(2)SiMe(3))(3) (M = Sc, 1; M = Y, 2) and tribenzyl complexes (L)M(CH(2)Ph)(3) (M = Sc, 3; M = La, 4). Complexes I and 2 can be converted to their corresponding ionic compounds [(L)M(CH(2)SiMe(3))(2)(THF)][B(C(6)H(5))(4)] (M = Sc, 5; M = Y, 6) by reaction with [PhNMe(2)H] [B(C(6)H(5))(4)] in THE Complexes 3 and 4 can be converted to cationic species [(L)M(CH(2)Ph)(2)](+) by reaction with [PhNMe(2)H][B(C(6)F(5))(4)] in C(6)D(5)Br in the absence of THE The neutral complexes 1-4 and their cationic derivatives were studied as catalysts for the hydroamination/cyclization of 2,2-diphenylpent-4-en-1-amine and N-methylpent-4-en-1-amine reference substrates and compared with ligand-free Sc, Y, and La neutral and cationic catalysts. The most effective catalysts in the series were the cationic L-yttrium catalyst (for 2,2-diphenylpent-4-en-1-amine) and the cationic lanthanum systems (for N-methylpent-4-en-1-amine). For the La catalysts, evidence was obtained for release of L from the metal during catalysis.