Improved Methodology for the Preparation of Chiral Amines

More documents

Recommendations

Info

Mohamed Mahmoud El-Shazly Curriculum Vitae Date of Birth: 09.April.1977 Mailing Address: Research III, Room 132 School of Engineering and Science Jacobs University, 28759, Bremen, Germany. Nationality: Egyptian E-mail: m.elshazly@jacobs-university.de, elshazly444@yahoo.com Phone: +49 160 557 9099 Academic Qualifications: Degree Month/Year University B.Sc. Pharmaceutical Science (Excellent with Honor, GPA 1.0) Post Graduate Diploma (Excellent, GPA 1.33) M.Sc. Nanomolecular science (Very Good, GPA 1.67) PhD Organic Chemistry Sep. 1995-Jun. 2000 Ain-Shams University, Cairo, Egypt. Sep. 2000-Jul. 2004 Ain-Shams University, Cairo, Egypt. Aug. 2004-Aug. 2006 Jacobs University, Bremen, Germany. Sep. 2006-Aug. 2009Jacobs University, Bremen, Germany. Academic awards/Honors: • Teaching and Research Assistantship, Department of Natural Product Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. • Best Teaching Award, Ain Shams University, Cairo, Egypt. • Best Presentation Skills, Ain Shams workshop for presentation skills. • Graduate Student Fellowship, Jacobs University for both MSc and PhD, Bremen, Germany. Membership: • American Chemical Association (ACS). • The Egyptian Federation of Red Cross and Red Crescent Societies. • International Pharmaceutical Federation (FIP). • Egyptian Pharmacists Syndicate (EPS). 154
Research experience: Date Project Sep. 2000- Jul. 2004 Phytochemical and Pharmacological Investigation of Natural Products Isolated from Stipagrostis scoparia Family Graminea.* Project description: Isolation of biologically active fractions with antihypertensive effect (dieresis and vasodilating effect) from Stipagrostis scoparia for the first time. Study the Application of Transfer Hydrogenation in Reductive Amination. Dec. 2004- Jun. 2005 Jun. 2005- Sep. 2005 Sep. 2005- Jan. 2006 Jan. 2006- Sep. 2006 Oct. 2006- Feb. 2007 Feb. 2007- Aug. 2007 Aug. 2007- Jun. 2008 Jun. 2008- Nov. 2008 Project description: Using chiral auxiliary (α-Methyl Benzyl Amine) as chiral nitrogen source with different hydrogen donors ( isopropanol, formic acid,..etc) and ruthenium or rhodium catalysts for reductive amination of different ketones. Conversion < 50% with 40% diastereoselectivity. Study the Effect of Additives on Asymmetric Reductive Amination. Project description: Testing the effect of different acidic and basic additives on the reductive amination of ketones. In general acidic compounds improved diastereoselectivity and vice versa for basic compounds. Synthesis of Different Carbenes and Testing their Application. Project description: Synthesizing different chiral amines and utilizing them as building blocks for chiral carbenes. Testing carbenes in enantioselective epoxide ring opening reactions. Study the Effect of Different Lewis Acids on Asymmetric Reductive Amination. Project description: Testing the effect of different available Lewis acids on diastereoselectivity of reductive amination. The use of Yb(OAc) 3 resulted in great enhancement of diastereoselectivity of 2-alaknones. Developing New Chiral Modifiers for Pt or Pd Metal Surface. Project description: Developing chiral cinchonidine analogues (chiral urea and thiourea derivatives) and testing their applications as modifiers for heterogeneous catalysts in asymmetric ketone reduction reactions. Synthesis of New Thiourea Organocatalysts and Testing their Application. Project description: Preparing different chiral thiourea derivatives and testing their applications in meso diol desymmetrization through using different acylating agents. Synthesis of New Formamide Organocatalysts and Testing their Application. Project description: Synthesizing different chiral formamide and testing their applications in the asymmetric allylation of aldehydes with allyltrichlorosilane. Synthesis of Novel Catalysts for Enantioselective Reductive Amination. Project description: Developing new air stable iridium chiral ligands and testing their applications in one pot enantioselective reductive amination without glovebox. Synthesis of Novel Chiral Amines on Multi-gram Scale. Nov. 2008- Feb. 2009 Project description: Preparing different α-chiral primary amines with >98% chemical purity and >98% enantioselectivity on multi gram scale (50 gram) utilizing large scale crystallization eliminating the need of chromatographic purification. * This project was carried out at Ain-Shams University Cairo Egypt. The rest of projects were carried out at 155
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 and 12:
Table of Contents Abstract. Acknowl
Page 13 and 14:
4.1.5. Synthesis of Emitine 85 4.1.
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
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 and 108:
ethyl carbamate by acylation with e
Page 109 and 110:
4.1.16. Synthesis of Ritonavir and
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
Page 159 and 160: Reaction details: Yb(OAc) 3 (1.1 eq
Page 161 and 162: etention time [min]: major (S,S)-2b
Page 163 and 164: time [min]: major (S,S)-2c isomer,
Page 165 and 166: obtain the hydrochloride salt (0.41
Page 167: with etheral HCl provided the hydro
show all

Improved Methodology for the Preparation of Chiral Amines

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?