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theses

In this thesis we summarize our efforts towards the development of binaphtholate and octahydrobinaptholate rare-earth metal complexes for asymmetric hydroamination of aminoalkenes, as well as kinetic resolution of chiral aminoalkenes via hydroamination. These complexes were also found to be efficient catalysts for the asymmetric intermolecular hydroamination of unactivated alkenes with simple amines. Catalytic screening results indicated that increasing steric bulk of the silyl-substituents in the ligand and decreasing ionic radius of the rare earth metal helped increase catalytic activity and enantioselectivity of the hydroamination product. Consistent with our previous findings, the hydroamination reaction catalyzed by these complexes showed zero order rate dependence on substrate concentration and first order rate dependence on catalyst concentration. In most cases, octahydrobinaphtholate complexes (R)-[Ln{L}(o-C6H4- CH2NMe2)(Me2NCH2Ph)] (Ln = Y, Lu; L = 3,3’-bis(triphenylsilyl)-5,5’,6,6’,7,7’, 8,8’-octahydro-1,1’-binaphthyl-2,2’-diolate (50a-Ln); L = 3,3’-bis(tert-butyldiphenyl silyl)-5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-binaphthyl-2,2’-diolate (50b-Ln); and L = 3,3’-bis(cyclohexyldiphenylsilyl)-5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-binaphthyl-2,2’-diolate (50c-Ln)) were shown to be more reactive and more enantioselective catalysts for asymmetric hydroamination than their related binaphtholate complexes (R)-[Ln{L}(o-C6H4CH2NMe2)(Me2NCH2Ph)] (Ln = Y, Lu; L = 3,3’-bis(triphenylsilyl)-1,1’-binaphthyl-2,2’-diolate (19a-Ln); L = 3,3’-bis(tert-butyldiphenylsilyl)-1,1’-binaphthyl-2,2’-diolate (39b-Ln); and L = 3,3’-bis(cyclohexyldiphenylsilyl)-1,1’-binaphthyl-2,2’-diolate (39c-Ln)). Turnover frequencies as high as 2400 h−1 were achieved for 2,2-diphenyl-pent-4-enylamine using (R)-50c-Y and enantiomeric excess of up to 98% could be obtained in the cyclization of C-(1-allylcyclohexyl)-methylamine using (R)-50c-Lu at room temperature. The stability of binaphtholate and octahydrobinaphtholate rare earth metal catalysts at elevated temperature of up to 150 C extended their usages for asymmetric intermolecular hydroamination of simple amines and unactivated alkenes, forming exclusively Markovnikov amine products. (R)-50a-Y displayed the high efficiency for catalytic addition of benzylamine to 4-phenyl-1-butene at 110 C, affording (R)-N-benzyl-4-phenylbutan-2-amine, with enantiomeric excess of up to 67%. The complexes were also suitable for kinetic resolution of chiral alpha-substituted aminoalkenes via catalytic asymmetric hydroamination. Kinetic resolution factors f of up to 90 and equilibrium constant Kdias of up to 5.1, indicating a Curtin-Hammett pre-equilibrium favoring the matching combination of substrate and complex, were observed for 1-methylpent-4-enylamine using (R)-39c-Y at 25 C. The 2,5-disubstituted pyrrolidines were formed in 7:1 to ≥ 50:1 trans diastereoselectivity, depending on the size of the alpha-substituent of the aminoalkene. Kinetic studies of (S)-1-methylpent-4-enylamine provided an access to activation parameters for matching pair (using (R)-39c-Y), ΔH‡ = 43(5) kJ mol−1, ΔS‡ = −136(17) J K−1 mol−1) and for mismatching pair (using (S)-39c-Y), trans diastereomer, ΔH‡ = 45(2) kJ mol−1, ΔS‡ = −160(7) J K−1 mol−1; cis diastereomer, ΔH‡ = 54(4) kJ mol−1, ΔS‡ = −130(14) J K−1 mol−1).

ETD_9199

Ph.D.

Includes bibliographical references

by Hiep Nhu Nguyen

doi:10.7282/t3-wk7m-d082

ETD doctoral

The author owns the copyright to this work.