Improved Methodology for the Preparation of Chiral Amines

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2.2.2. Different Substrates Categories 36 2.2.3. Nguyen Special Substrates 39 2.3. Asymmetric Reduction of N-aryl imines 40 2.3.1. Synthesis of N-Aryl Imines 40 2.3.2. Different Substrates Categories 43 2.4. Reduction of Miscellaneous Imines 49 2.5 Conclusion 49 2.6. References 50 3. Reductive Amination 3.1. Historical View 53 3.1.1. Reductive Amination Utilizing Heterogeneous Catalyst 53 3.1.2. Reductive Amination Utilizing Homogenous Catalysis 55 3.2. Reductive Amination the Current State of Art 57 3.3. Asymmetric Reductive Amination 60 3.3.1. Asymmetric Reductive Amination Utilizing Chiral Catalysts 60 3.3.2. Reductive Amination Utilizing Chiral Auxiliary 64 3.3.3. Reductive Amination Utilizing Molecular Hydrogen 65 3.3.4. Asymmetric Reductive Amination Utilizing Transfer Hydrogenation Conditions 66 3.4.5. Organocatalytic Asymmetric Reductive Amination 67 3.4. Green Chemistry and Reductive Amination 73 3.4.1. Green Chemistry Basic principle 73 3.4.2. Hydrogenation and Green Chemistry 75 3.5. Conclusion 76 3.6. References 76 4. Drugs and Reductive Amination 4.1 Reductive Amination in the Synthesis of Drugs and Natural Products 81 4.1.1. Synthesis of Delavirdine 81 4.1.2. Synthesis of Muraglitazar 82 4.1.3. Synthesis of Amphetamine 83 4.1.4. Synthesis of Sertraline 84 ix
4.1.5. Synthesis of Emitine 85 4.1.6. Synthesis of Taltobulin 86 4.1.7. Synthesis of Perzinfote 87 4.1.8. Synthesis of Namindinil 88 4.1.9. Synthesis of Ezlopipant 89 4.1.10.Synthesis of Monomorine 90 4.1.11. Synthesis of Ontazolast 91 4.1.12. Synthesis of Pamaquine 92 4.1.13. Synthesis of Torcetrapib 92 4.1.14. Synthesis of Polyaminocholestanol Derivatives 93 4.1.15. Synthesis of piperazinylpropylisoxazoline Analogues 94 4.1.16. Synthesis of Ritonavir and Lopinavir 95 4.1.17. Synthesis of Tetrahydrocarbazoles 95 4.2. Conclusion 97 4.3. References 97 5. Stoichiometric Use of Ytterbium Acetate in Reductive Amination. 5.1. Introduction 98 5.1.1. Ytterbium 100 5.1.1.1. Electronic Overview 100 5.1.1.2. Ytterbium Discovery 101 5.1.1.3. Ytterbium Reactions 101 5.1.1.4. Ytterbium Acetate 102 5.1.2. Commercial Yb(OAc) 3 vs Dried Yb(OAc) 3 110 5.1.3. Optimized Conditions and Useful Substrate Range 112 5.2. Conclusion 115 5.3. References 115 6. Catalytic Lewis Acids in Reductive Amination 6.1. Introduction 117 6.2. Brønsted Acid Promoted Reductive Amination 122 6.3. Conclusion 125 6.4. References 125 x
Page 1 and 2: Improved Methodology for the Prepar
Page 3 and 4: This dissertation is dedicated to a
Page 5 and 6: suppressing alcohol formation and p
Page 7 and 8: Prof. Mohamed El-Azizi, Prof. Abdel
Page 9 and 10: Et EtOH EtOAc GC h HPLC HRMS Hz J K
Page 11: Table of Contents Abstract. Acknowl
Page 15 and 16: Chapter 1 Introduction 1.1. Chiral
Page 17 and 18: 1. Cis-trans or geometric isomers.
Page 19 and 20: O O O * NH Thalidomide (R)-active a
Page 21 and 22: One enantiomer may be responsible f
Page 23 and 24: 1.5.1. Synthesis of Enantiomericall
Page 25 and 26: 1.5.2.2. Kinetic Resolution Kinetic
Page 27 and 28: compound by the auxiliary. The auxi
Page 29 and 30: 1.5.4. Stereoselective Conversion o
Page 31 and 32: It is estimated that 3000 tonnes (a
Page 33 and 34: k R R P 1 k rac S k S P 2 Figure 1.
Page 35 and 36: (S)-(α)-Methylbenzylamine and its
Page 37 and 38: fourth chapter showing different dr
Page 39 and 40: Burk was successful in reducing ary
Page 41 and 42: Table 1.1 Rhodium Catalyzed Reducti
Page 43 and 44: [8] E. L. Eliel, S. H. Wilen, Stere
Page 45 and 46: [42] a) J. Blacker, Innovations in
Page 47 and 48: [67] a) H. Qin, N. Yamagiwa, S. Mat
Page 49 and 50: of imine reduction in the past eigh
Page 51 and 52: 8 years beginning from the year 200
Page 53 and 54: 2.2.3. Nguyen Special Substrates. A
Page 55 and 56: Figure 2.4 General Catalyst structu
Page 57 and 58: 2.3.2. Different Substrates Categor
Page 59 and 60: H 2 , toluene, 25 °C, 4 h an ee of
Page 61 and 62: 1). They described the role of each
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More recently, 2008, he described t
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[22] E. Guiu, M. Aghmiz, Y. Diaz, C
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Chapter 3 Reductive Amination 3.1.
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. CH 3 CO(CH 2 ) 5 CH 3 H 2 NCH 2 C
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superior in terms of conversion (89
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O NHR 3 R 4 R 4 R 3 N OTi(O i Pr) 3
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Scheme 3.9. Synthesis of (S)-Metola
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groups decreased both the enantiose
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progress of the reaction was monito
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attempts were directed for the asym
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hydrogen bonding, is chiral and its
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Later he utilized this methodology
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OMe OMe O HN HN HN O 2 N 71 % yield
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compared to the oil refinery indust
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[14] V. I. Tararov, R. Kadyrov, T.H
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[55] a) R. Kadyrov, T. H. Riermeier
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Chapter 4 Drugs and Reductive Amina
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Scheme 4.2. Synthesis of Muraglitaz
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Studies showed that the active isom
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aminoacid producing the protected a
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O NH 2 1. p-TsOH/toluene 2. BH 3 -T
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O O 125 NH 2 a 93% O O 126 H Bu N T
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ethyl carbamate by acylation with e
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4.1.16. Synthesis of Ritonavir and
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4.2. Conclusion Different important
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Chapter 5 Stoichiometric Use of Ytt
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The unique feature of this methodol
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Ytterbium triflate is the most comm
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Ruthenium(III) chloride 31.7 4 4.2
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t-Butyl methyl ether 15 - - 82 Hexa
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2-octanone starting material. When
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3 Yb(OTf) 3 d 4 Ti(O i Pr) 4 e 5 B(
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If a [1,3]-proton shift of the init
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enhanced stereoselectivity. For exa
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WO2006030017, 2006; c) T. C. Nugent
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4 60 86 5 50 86 6 40 84 7 20 79 8 2
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The reactions described above all u
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e.g. compare entries 1, 5, 6, and 9
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solvent in the stoichiometric and c
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[2] Farina, V.; Grozinger, K.; Mül
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congested which should be favored.
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imine area % (GC analysis) time (mi
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Inversion at the nitrogen atom of t
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anti-6) would be expected to have m
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e.g. AcOH, suppresses alcohol by-pr
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eductive amination of a prochiral k
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Appendix Experimental Section Gener
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and the mixture was stirred for 30
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Reaction details: Yb(OAc) 3 (1.1 eq
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etention time [min]: major (S,S)-2b
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time [min]: major (S,S)-2c isomer,
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obtain the hydrochloride salt (0.41
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with etheral HCl provided the hydro
Page 169 and 170:
Research experience: Date Project S
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Improved Methodology for the Preparation of Chiral Amines

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