Ph.D. Thesis_AS_Publishing version for IRC_12 ... - Jacobs University

More documents

Recommendations

Info

Chapter 1 H 3 C O O H 3 C O (S)-proline (3 mol%) DMF O H 3 C OH O Scheme 1.2. First proline catalyzed asymmetric aldol reaction. 100% yield, 93% ee Despite the publications of these early examples of organocatalysis, the concept was not further explored. At that time, the mechanisms were not clear and the applications were limited. 5 After 30 years of essentially dormant existence, the field was brought to life with the discovery of proline-catalyzed asymmetric intermolecular aldol reactions. 6 In the same year MacMillan reported the first enantioselective organocatalytic Diels-Alder reaction (Scheme 1.3). 7 Ph O Ph Me O Catalyst (20 mol%) MeOH-H 2 O 23 o C Ph O Ph Me CHO Yield = 75% exo:endo = 35:1 ee = 96% Ph O N H Me N Me Me Catalyst HCl Scheme 1.3. First enantioselective organocatalytic Diel-Alder reaction. In the past, metal complexes provided flexible bases for most new reactions and has been developed to a high level as compared to organocatalysis. Currently the picture of asymmetric catalysis is changing and organocatalysis is becoming an increasingly important complementary topic which can be at times a competive alternative to metal based catalysis. This increasing tendency for asymmetric organocatalysis happens because of the benefits that they can sometimes provide: • High catalytic activity • Easily available 3
Chapter 1 • Easy and promising preparation • Low price • Low molecular weight • Easily separable from reaction mixture • Recycling after workup • Non toxic • Stable Today, reactions can be performed under an aerobic atmosphere, with wet solvents; sometimes, the presence of water is beneficial to the rate and selectivity of the reaction. 8 The operational simplicity and availability of these inexpensive bench-stable catalysts makes organocatalysis, in general, an attractive method for the synthesis of complex structures. 9 Furthermore, unlike earlier developed organic fields, organocatalysis provides a rich platform for multistep or tandem reactions, 10 allowing easy to important building blocks for drug or natural product synthesis. 1.2 Enamine catalysis An enamine is an unsaturated compound formed by the nucleophilic attack of a secondary amine on an aldehyde or ketone followed by the loss of H 2 O. Earlier literature reveals that enamines can be used as enolate equivalents, 11 therefore enamines can be used to attack the electrophiles. This nucleophilic character of enamines makes them useful intermediates in a variety of organocatalytic reactions. In 2000, List and Barbas 6a demonstrated for the first time intermolecular aldol reactions between acetone and a variety of aldehydes (Scheme 1.4). They use a high loading of (S)-proline (30 mol%) to catalyze their reactions. The authors mentioned that proline most likely functions as a micro-aldolase, the aldolase antibodies they had created 12 and natural aldolase enzyme aldolase A. So they strongly believed that (S)-proline was also working through an enamine intermediate. Afterwards, List went on to expand the application of this reaction for the synthesis of chiral 1,2- diols by reacting hydroxy acetones with aldehydes. 13 4
Page 1 and 2: Bifunctional Organocatalysts Contai
Page 3 and 4: Acknowledgements I would like to co
Page 5 and 6: EtOAc GC h HPLC HRMS Hz IR J m M Me
Page 7 and 8: Abstract The asymmetric Michael add
Page 9 and 10: 1.5 Research goals: bifunctional ba
Page 11 and 12: Chapter 6. Spectra (HPLCs and NMRs)
Page 13: Chapter 1 1.1 Organocatalysis In pa
Page 17 and 18: Chapter 1 Scheme 1.5 shows a possib
Page 19 and 20: Chapter 1 O O O N R (S)-proline DMS
Page 21 and 22: Chapter 1 1.4 Asymmetric Michael ad
Page 23 and 24: Chapter 1 O R Michael product R' Ar
Page 25 and 26: Chapter 1 bifunctional catalysts st
Page 27 and 28: Chapter 1 proposed that the seconda
Page 29 and 30: Chapter 1 Ph NH 2 Ph N H S N H NH N
Page 31 and 32: Chapter 1 Amino-sulfoneamides N H 2
Page 33 and 34: Chapter 1 acetone with only 16% ee.
Page 35 and 36: Chapter 1 X X NH 2 COOK NH N Cl 46
Page 37 and 38: Chapter 1 O O O O O O S O 50 51 52
Page 39 and 40: Chapter 1 Summary for the asymmetri
Page 41 and 42: Chapter 1 4 25b 13 / 5 7 120 rt 63
Page 43 and 44: Chapter 1 Table 1.4: Summary for th
Page 45 and 46: Chapter 1 20 48a O H O O N Ph 15/10
Page 47 and 48: Chapter 1 References 1. Selected re
Page 49 and 50: Chapter 1 33. B. Tan, X. Zeng, Y. L
Page 51 and 52: Chapter 2 RESULTS AND DISCUSSION: D
Page 53 and 54: Chapter 2 enamine. Meanwhile, the p
Page 55 and 56: Chapter 2 2.3 Model reaction: cyclo
Page 57 and 58: Chapter 2 2.1, entry 3). THF and a
Page 59 and 60: Chapter 2 2.4 Asymmetric Michael ad
Page 61 and 62: Chapter 2 Table 2.4: Asymmetric Mic
Page 63 and 64: Chapter 2 Ph NH N H H N Ph NH 97 98
Page 65 and 66:
Chapter 2 A final convincing argume
Page 67 and 68:
Chapter 2 References 1. S. H. McCoo
Page 69 and 70:
Chapter 3 3.1 Introduction Asymmetr
Page 71 and 72:
Chapter 3 ineraction, as shown in S
Page 73 and 74:
Chapter 3 CF 3 CF 3 O S O O H 2 N N
Page 75 and 76:
Chapter 3 Table 3.2: Solvent screen
Page 77 and 78:
Chapter 3 4 71 99 10 O t Bu-L-threo
Page 79 and 80:
Chapter 3 Table 3.4: Asymmetric Mic
Page 81 and 82:
Chapter 3 20 B H O O N Ph O 134 16
Page 83 and 84:
Chapter 3 16 [b], [d] 1,2-dimethoxy
Page 85 and 86:
Chapter 3 To better appreciate the
Page 87 and 88:
Chapter 3 Ph Me O 3.20 tBuO Ph N N
Page 89 and 90:
Chapter 3 Figure 3.4. Steric based
Page 91 and 92:
Chapter 3 permit fundamentally diff
Page 93 and 94:
Chapter 3 These combined results de
Page 95 and 96:
Chapter 3 1 H NMR (400 MHz, CDCl 3
Page 97 and 98:
Chapter 3 methyl group of the minor
Page 99 and 100:
Page 101 and 102:
Chapter 3 Figure 3.13. Expansion fr
Page 103 and 104:
Page 105 and 106:
Chapter 3 Please refer to α-ethyl
Page 107 and 108:
Chapter 3 13 C NMR (100 MHz, CDCl 3
Page 109 and 110:
Chapter 3 129.19, & 131.93 ppm repr
Page 111 and 112:
Chapter 3 References 1. For the reg
Page 113 and 114:
Chapter 3 19. The potassium complex
Page 115 and 116:
Chapter 4 4.1 General information A
Page 117 and 118:
Chapter 4 4.3 Racemate formation 4.
Page 119 and 120:
Chapter 4 O NO 2 (S)-2-((R)-2-nitro
Page 121 and 122:
Chapter 4 MS (EI), m/z (relative in
Page 123 and 124:
Chapter 4 References 1. The two ena
Page 125 and 126:
Chapter 5 5.1 General information R
Page 127 and 128:
Chapter 5 5.2 Racemate formation To
Page 129 and 130:
Chapter 5 The ee was determined by
Page 131 and 132:
Chapter 5 (S)-1-(2,5-dioxo-1-phenyl
Page 133 and 134:
Chapter 5 (S)-3-(benzo[d][1,3]dioxo
Page 135 and 136:
Chapter 5 (S)-2,6-dimethyl-2-((S)-2
Page 137 and 138:
Page 139 and 140:
Chapter 6 SPECTRA (HPLCs AND NMRs)
Page 141 and 142:
Chapter 6 HPLC of 2,2,2-trifluoro-N
Page 143 and 144:
Chapter 6 HPLC of 2-(2-nitro-1-p-to
Page 145 and 146:
Chapter 6 HPLC of 2-(1-(furan-2-yl)
Page 147 and 148:
Chapter 6 HPLC of 2,2-dimethyl-4-ni
Page 149 and 150:
Chapter 6 HPLC of 3-(4-methoxypheny
Page 151 and 152:
Chapter 6 140
Page 153 and 154:
Chapter 6 142
Page 155 and 156:
Chapter 6 144
Page 157 and 158:
Chapter 6 146
Page 159 and 160:
Chapter 6 148
Page 161 and 162:
Chapter 6 150
Page 163 and 164:
Chapter 6 HPLC of 2-(1-benzyl-2,5-d
Page 165 and 166:
Chapter 6 HPLC of 1-(2,5-dioxo-1-ph
Page 167 and 168:
Page 169 and 170:
Page 171 and 172:
Chapter 6 HPLC of 3-(benzo[d][1,3]d
Page 173 and 174:
Chapter 6 HPLC of 2-methyl-2-(2,5-d
Page 175 and 176:
Chapter 6 164
Page 177 and 178:
Chapter 6 166
Page 179 and 180:
Chapter 6 168
Page 181 and 182:
Chapter 6 170
Page 183 and 184:
Chapter 6 172
Page 185 and 186:
Chapter 6 174
Page 187 and 188:
Chapter 6 176
Page 189 and 190:
Chapter 6 178
Page 191 and 192:
Chapter 6 180
Page 193 and 194:
Chapter 6 182
Page 195 and 196:
Chapter 6 184
Page 197:
Publication # 02 Sequential Reducti
show all

Ph.D. Thesis_AS_Publishing version for IRC_12 ... - Jacobs University

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

Delete template?

Save as template?