Improved Methodology for the Preparation of Chiral Amines

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AcO H O 1) Ti(O i Pr) 4 ,MeOH 20 o C, 5-6 h 2) NaBH 4 ,-78 o C,2 h RNH 2 3) K 2 CO 3 , MeOH/THF (1:1) rt, 12 h AcO H NH 2 R Scheme 4.14. Synthesis of Polyaminocholestanol Derivatives. 4.1.15. Synthesis of Piperazinylpropylisoxazoline Analogues: Piperazinylpropylisoxazoline analogues are potent ligands for dopamine receptors which have strong influence on the general psychological condition. [10] Synthesis is accomplished through the reductive amination of enantiomerically pure (S) or (R) aldehyde (1) with different piprazine derived amines. The (R) isomer showed higher potent activity for dopamine receptors. O H (S)-1 O N R 1 (S)-1 or (R)-1 N N N O N R 1 R 2 N H or R 2 O N R 1 R 2 N N Scheme 4.15. Synthesis of piperazinylpropylisoxazoline analogues. 94
4.1.16. Synthesis of Ritonavir and Lopinavir: Ritonavir and lopinavir are HIV-protease inhibitors. Their synthesis depends on the synthesis of chiral aminoalcohols. [11] Titanium isopropoxide with polymethylhydrosiloxane (hydride source) and p-anisidine were utilized for the synthesis of aminoalcohols under reductive amination conditions. Aliphatic, cyclic, as well as aromatic and heteroaromatic hydroxyketones were tested showing good to high yields (76-89%) with good stereoselectivities (de 72-86%). R 1 OH O R 2 NR 3 H 2 Ti(O i Pr) 4 PMHS R 1 O N R 2 H + TiLn OH NR 3 H R 1 R 3 R 2 S N CH 3 N O H N O Ph NH OH Ph H N O O S N HN O N O Ph NH OH Ph H N O O Ritonavir Lopinavir Scheme 4.16. Synthesis of Aminoalcohols the Core of Ritonavir and Lopinavir: 4.1.17. Synthesis of Tetrahydrocarbazoles: Tetrahydrocarbazoles is an efficient compound for the treatment of human papillomaviruses (HPVs). [12] HPV infection is considered the most common sexually transmitted disease throughout the world. There are over 5.5 million new cases of sexually transmitted HPV in the United States each year, with at least 20 million people currently infected. The chiral centre in the molecule is the α-chiral amine in which its synthesis represents the key step in the synthesis of this tetrahydrocarbazoles. In their initial attempts for building this chiral moiety they tested chemical resolution. The best results were obtained utilizing dibenzoyl-Dtartaric acid leading to 86% ee with only 13% yield. This low yield encouraged them to shift to the asymmetric synthesis for building the chiral centre. Noyori catalyst was tested for the 95
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Improved Methodology for the Prepar
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This dissertation is dedicated to a
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suppressing alcohol formation and p
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Prof. Mohamed El-Azizi, Prof. Abdel
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Et EtOH EtOAc GC h HPLC HRMS Hz J K
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Table of Contents Abstract. Acknowl
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4.1.5. Synthesis of Emitine 85 4.1.
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Chapter 1 Introduction 1.1. Chiral
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1. Cis-trans or geometric isomers.
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O O O * NH Thalidomide (R)-active a
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One enantiomer may be responsible f
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1.5.1. Synthesis of Enantiomericall
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1.5.2.2. Kinetic Resolution Kinetic
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compound by the auxiliary. The auxi
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1.5.4. Stereoselective Conversion o
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It is estimated that 3000 tonnes (a
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k R R P 1 k rac S k S P 2 Figure 1.
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(S)-(α)-Methylbenzylamine and its
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fourth chapter showing different dr
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Burk was successful in reducing ary
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Table 1.1 Rhodium Catalyzed Reducti
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[8] E. L. Eliel, S. H. Wilen, Stere
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[42] a) J. Blacker, Innovations in
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[67] a) H. Qin, N. Yamagiwa, S. Mat
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of imine reduction in the past eigh
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8 years beginning from the year 200
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2.2.3. Nguyen Special Substrates. A
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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
Page 63 and 64: More recently, 2008, he described t
Page 65 and 66: [22] E. Guiu, M. Aghmiz, Y. Diaz, C
Page 67 and 68: Chapter 3 Reductive Amination 3.1.
Page 69 and 70: . CH 3 CO(CH 2 ) 5 CH 3 H 2 NCH 2 C
Page 71 and 72: superior in terms of conversion (89
Page 73 and 74: O NHR 3 R 4 R 4 R 3 N OTi(O i Pr) 3
Page 75 and 76: Scheme 3.9. Synthesis of (S)-Metola
Page 77 and 78: groups decreased both the enantiose
Page 79 and 80: progress of the reaction was monito
Page 81 and 82: attempts were directed for the asym
Page 83 and 84: hydrogen bonding, is chiral and its
Page 85 and 86: Later he utilized this methodology
Page 87 and 88: OMe OMe O HN HN HN O 2 N 71 % yield
Page 89 and 90: compared to the oil refinery indust
Page 91 and 92: [14] V. I. Tararov, R. Kadyrov, T.H
Page 93 and 94: [55] a) R. Kadyrov, T. H. Riermeier
Page 95 and 96: Chapter 4 Drugs and Reductive Amina
Page 97 and 98: Scheme 4.2. Synthesis of Muraglitaz
Page 99 and 100: Studies showed that the active isom
Page 101 and 102: aminoacid producing the protected a
Page 103 and 104: O NH 2 1. p-TsOH/toluene 2. BH 3 -T
Page 105 and 106: O O 125 NH 2 a 93% O O 126 H Bu N T
Page 107: ethyl carbamate by acylation with e
Page 111 and 112: 4.2. Conclusion Different important
Page 113 and 114: Chapter 5 Stoichiometric Use of Ytt
Page 115 and 116: The unique feature of this methodol
Page 117 and 118: Ytterbium triflate is the most comm
Page 119 and 120: Ruthenium(III) chloride 31.7 4 4.2
Page 121 and 122: t-Butyl methyl ether 15 - - 82 Hexa
Page 123 and 124: 2-octanone starting material. When
Page 125 and 126: 3 Yb(OTf) 3 d 4 Ti(O i Pr) 4 e 5 B(
Page 127 and 128: If a [1,3]-proton shift of the init
Page 129 and 130: enhanced stereoselectivity. For exa
Page 131 and 132: WO2006030017, 2006; c) T. C. Nugent
Page 133 and 134: 4 60 86 5 50 86 6 40 84 7 20 79 8 2
Page 135 and 136: The reactions described above all u
Page 137 and 138: e.g. compare entries 1, 5, 6, and 9
Page 139 and 140: solvent in the stoichiometric and c
Page 141 and 142: [2] Farina, V.; Grozinger, K.; Mül
Page 143 and 144: congested which should be favored.
Page 145 and 146: imine area % (GC analysis) time (mi
Page 147 and 148: Inversion at the nitrogen atom of t
Page 149 and 150: anti-6) would be expected to have m
Page 151 and 152: e.g. AcOH, suppresses alcohol by-pr
Page 153 and 154: eductive amination of a prochiral k
Page 155 and 156: Appendix Experimental Section Gener
Page 157 and 158: 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
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Research experience: Date Project S
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Improved Methodology for the Preparation of Chiral Amines

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