Synthesis and Comparison of the Reactivity of Allyl Fluorides and ...

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160 Chapter Six = 16.8 Hz, 2 JHH = 4 JHH = 0.8 Hz, Ha), 5.85 (1H, ddd, 3 JHH = 17.2 Hz, 3 JHH = 10.2 Hz, 3 JHH = 7.8 Hz, Hc), 7.20–7.31 (5H, ArH); δC 60.1 (CHCl), 73.4 (CH2Ar), 73.6 (OCH2), 118.6 (CHCH2), 127.7 (ArCH-3), 127.9 (ArCH-4), 128.5 (ArCH-2), 135.5 (CHCH2), 137.7 (ArC- 1). m/z (EI + ) 196 ([M] + , 15 %) 91 ([M-OCH2CHClCH=CH2] + , 100 %). HRMS (EI) 196.06512 (C11H13OCl requires 196.06517). 6.2.35 Preparation of ((4-chlorobut-2-enyloxy)methyl)benzene (107) [12] The rearranged chloride product was also isolated from the synthesis of ((4-chlorobut-2-enyloxy)methyl) benzene, as an oil (0.06 g, 15 %); δH 3.96 (2H, dm, 2 JHH = 11.7 Hz), 3.99 (2H, dm, 3 JHH = 5.5 Hz,), 4.44 (2H, AB, 2 JAB = 12.5 Hz, CHAHBAr), 5.73-5.87 (2H, m, Ha and Hb), 7.18–7.30 (5H, ArH); δC 44.4 (CH2Cl), 69.5 (CH2Ar), 72.4 (OCH2), 127.7 (ArCH-3), 127.8 (ArCH-4), 128.4 (CHCH2Cl), 128.5 (ArCH-2), 1 31.2 (CHCH2O), 138.1 (ArC-1). 6.2.36 Preparation of 2-chlorobut-3-enyl benzoate (108) The title compound was prepared following the method outlined by Munyemana et al. [11] A 100 cm 3 , three- necked round-bottom flask was equipped with a magnetic stirring bar and Rotaflo tap and attached to a Schlenk line. After flame-drying under high vacuum, the flask was cooled and filled with nitrogen. The reaction flask was then charged with 2-hydroxybut-3-enyl benzoate (1.24 g, 6.45 mmol) and anhydrous DCM (25 cm 3 ). The flask was cooled to 0 ºC using an ice bath. Once cooled tetramethyl-�-chloroenamine was added (0.88 cm 3 , 6.45 mmol) via syringe. The reaction mixture was then stirred at room temperature for 3 h. After which purification by chromatography [DCM: cyclohexane (50:50)] afforded the product as an oil (0.88 g, 65 %). δH 4.38 (1H, dd, 2 JHH = 11.3 Hz, 3 JHH = 7.0 Hz, Hd), 4.42 (1H, dd, 2 JHH = 11.3 Hz, 3 JHH = 5.9 Hz, He), 4.55-4.61 (1H, m, CHCl), 5.20 (1H, ap.dt, 3 JHH = 10.2 Hz, 2 JHH = 4 JHH = 0.8 Hz, Hb), 5.35 (1H, ap.dt, 3 JHH = 16.8 Hz, 2 JHH = 4 JHH = 0.8 Hz, Ha), 5.86 (1H, ddd, 3 JHH = 16.8 Hz, 3 JHH = 10.2 Hz, 3 JHH = 7.8 Hz, Hc), 7.34 (2H, tm, 3 JHH = 7.8 Hz, ArH-3), 7.46 (1H, tt, 3 JHH = 7.4 Hz, 4 JHH = 2.0 Hz, ArH-4), 7.34 (2H, dm, 3 JHH = 8.2 Hz, ArH-2); δC 58.8 (CHCl), 67.1 (OCH2), 119.4 (CHCH2), 128.5 (ArCH-3), 129.7 (ArC-1), 129.8 (ArCH-2), 133.3 (CHCH2), 134.5 (ArCH-4), 165.9 (C=O). m/z (EI + ) 210 ([M] + , 5 %) 105 ([M- OCH2CHClCH=CH2] + , 100 %). HRMS (EI) 210.04455 (C11H11O2Cl requires 210.04448).
6.2.37 Preparation of 2-chlorobut-3-enyl 4-fluorobenzoate (109) 161 Chapter Six The novel compound was prepared following the method outlined by Munyemana et al. [11] A 100 cm 3 , three-necked round-bottom flask was equipped with a magnetic stirring bar and Rotaflo tap and attached to a Schlenk line. After flame-drying under high vacuum, the flask was cooled and filled with nitrogen. The reaction flask was then charged with 2-hydroxybut-3- enyl 4-fluorobenzoate (1.0 g, 4.75 mmol) and anhydrous DCM (25 cm 3 ). The flask was then cooled to 0 ºC using an ice bath. Once cooled tetramethyl-�-chloroenamine was added (0.64 cm 3 , 4.75 mmol) via syringe. The reaction mixture was then stirred at room temperature for 3 h. After which purification by chromatography [DCM: cyclohexane (50:50)] afforded the product as an oil (0.80 g, 74 %). δH 4.38 (1H, dd, 2 JHH = 11.3 Hz, 3 JHH = 7.0 Hz, Hd), 4.42 (1H, dd, 2 JHH = 11.3 Hz, 3 JHH = 5.9 Hz, He), 4.55-4.61 (1H, m, CHCl), 5.20 (1H, ap.dt, 3 JHH = 10.2 Hz, 2 JHH = 4 JHH = 0.8 Hz, Hb), 5.35 (1H, ap.dt, 3 JHH = 16.8 Hz, 2 JHH = 4 JHH = 0.8 Hz, Ha), 5.86 (1H, ddd, 3 JHH = 16.8 Hz, 3 JHH = 10.2 Hz, 3 JHH = 7.8 Hz, Hc), 7.05 (2H, ap.t, 3 JHH = 3 JHF = 8.6 Hz, ArH-3), 8.00 (2H, dd, 3 JHH = 9.0 Hz, 4 JHF = 5.1 Hz, ArH-2); δC 58.7 (CHCl), 67.2 (OCH2), 115.7 (d, 2 JCF = 22.1 Hz, ArCH-3), 119.5 (CHCH2), 125.9 (d, 4 JCF = 3.0 Hz, ArC-1), 132.3 (d, 3 JCF = 10.1 Hz, ArCH-2), 134.4 (CHCH2), 165.0 (C=O), 166.0 (d, 1 JCF = 254.6 Hz, ArCF); δF -105.4 (1F, s, CF). m/z (EI + ) 228 ([M] + , 22 %) 123 ([M-OCH2CHClCH=CH2] + , 100 %). HRMS (EI) 228.03504 (C11H10O2ClF requires 228.03509). 6.2.38 Preparation of 2-chlorobut-3-enyl 3-fluorobenzoate (110) The novel compound was prepared following the method outlined by Munyemana et al. [11] A 100 cm 3 , three-necked round-bottom flask was equipped with a magnetic stirring bar and Rotaflo tap and attached to a Schlenk line. After flame-drying under high vacuum, the flask was cooled and filled with nitrogen. The reaction flask was then charged with 2- hydroxybut-3-enyl 3-fluorobenzoate (0.2 g, 2.46 mmol) and anhydrous DCM (15 cm 3 ). The flask was then cooled to 0 ºC using an ice bath. Once cooled tetramethyl-�-chloroenamine was added (0.36 cm 3 , 2.71 mmol) via syringe. The reaction mixture was then stirred at room temperature for 3 h. After which purification by chromatography [DCM: cyclohexane
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Synthesis and Comparison of the Rea
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Acknowledgements Firstly, I would l
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2.2.2.1.1 Synthesis of 1-(Benzyloxy
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6.2.12 Preparation of 2-(4-trimethy
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6.4.12 Experimental Data for Dimeth
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AgF ap Bn Bz CsF d DAST dba DCM DME
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Chapter one
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2 Chapter One potentially explosive
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4 Chapter One ortho-biphenyl trifla
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6 Chapter One 2,10 (3,3-dichlorocam
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8 Chapter One both enantiomers were
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10 Chapter One poor to moderate ena
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Scheme 1.10 Fluorination of (17) 12
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14 Chapter One fluorine donors, Lew
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1.3 Enantioselective Nucleophilic F
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Scheme 1.16 Fluorination of (32) 18
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20 Chapter One (iii) SN2’ type su
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22 Chapter One cytotoxicity in the
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24 Chapter One Manabe and Ishikawa
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Scheme 1.25 Synthesis of (41)-(44)
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Figure 1.12 �-fluorinated NSAIDs
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1.6 Thesis Outline 30 Chapter One T
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32 Chapter One [26] M. Abdul-Ghani,
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[79] M. Schlosser, D. Michael, Z.-W
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2.1 Introduction 2 Synthesis of All
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37 Chapter Two In dehydroxyfluorina
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Scheme 2.6 Fluorination with IF5/Et
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41 Chapter Two desired allylic fluo
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43 Chapter Two c) Formation of a su
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Scheme 2.14 Reaction of cis-3-methy
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Substrate (60) (61) (62) (63) R = O
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Alcohol Product Yield (%) Table 2.7
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51 Chapter Two completion. This ena
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53 Chapter Two Chapter Three. Follo
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55 Chapter Two Two allyl alcohols w
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57 Chapter Two The conversion of (8
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Starting substrate (88) (89) (90) (
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Starting substrate (99) (76) (77) (
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63 Chapter Two Both (105) and (104)
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Scheme 2.25 Mechanistic pathway for
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2.3 Conclusions 67 Chapter Two The
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[28] D. F. Taber, J. Am. Chem. Soc.
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Chapter THRee
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72 Chapter Three Kurosawa reacted a
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74 Chapter Three These results demo
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76 Chapter Three More recently, wor
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3.2 Results and Discussion 3.2.1 Re
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80 Chapter Three Starting substrate
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82 Chapter Three Figure 3.4 Crystal
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Scheme 3.12 Oxidative addition of 1
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86 Chapter Three when the reaction
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88 Chapter Three Therefore, from th
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-140 -140 -140 -140 -140 -150 -150
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92 Chapter Three monitored for 80 m
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3.4 References [1] W. T. Dent, R. L
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Chapter Four
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97 Chapter Four nucleophilic substi
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99 Chapter Four Further reactions w
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Figure 4.3 Structure of co-product
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4.2.2 Reactions of palladium cation
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105 Chapter Four substituents on th
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107 Chapter Four The desired produc
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109 Chapter Four The reaction of (1
Page 127 and 128: 111 Chapter Four were both reacted
Page 129 and 130: [28] D. Landini, A. Maia, A. Rampol
Page 131 and 132: 5.1 Introduction 5 Synthesis and Re
Page 133 and 134: 116 Chapter Five The first enantios
Page 135 and 136: 118 Chapter Five Gem(difluoroallyl)
Page 137 and 138: 120 Chapter Five benzaldehyde, 3-br
Page 139 and 140: Starting Substrate (76) (77) (78) (
Page 141 and 142: Starting Substrate Product Yield (%
Page 143 and 144: 5.2.4 Synthesis of Allylic Difluori
Page 145 and 146: 5.2.5 Metal-mediated synthesis of 3
Page 147 and 148: 130 Chapter Five process. [40] Unfo
Page 149 and 150: 132 Chapter Five compounds were pur
Page 151 and 152: 134 Chapter Five [30] H. L. Sham, N
Page 153 and 154: 6.1 General Experimental Procedures
Page 155 and 156: 6.2 Experimental Details for Chapte
Page 157 and 158: 139 Chapter Six (1 g, 0.75 cm 3 , 6
Page 159 and 160: 6.2.7 Preparation of allyl 4-(trifl
Page 161 and 162: 6.2.10 Preparation of (3-[1,3]Dioxa
Page 163 and 164: 145 Chapter Six reaction mixture wa
Page 165 and 166: 147 Chapter Six mg, 1.1 mmol), ally
Page 167 and 168: 149 Chapter Six 260.3 Hz, ArCF), 16
Page 169 and 170: 6.2.22 Preparation of 2-fluorobut-3
Page 171 and 172: 6.2.25 Preparation of 2-fluorobut-3
Page 173 and 174: 6.2.28 Preparation of 2-hydroxybut-
Page 175 and 176: 157 Chapter Six 1 JCF = 253.5 Hz, A
Page 177: 159 Chapter Six drying under high v
Page 181 and 182: 6.2.40 Preparation of 2-chlorobut-3
Page 183 and 184: 6.3.2 Preparation of Bis[�-chloro
Page 185 and 186: 167 Chapter Six 6.3.5 Preparation o
Page 187 and 188: 169 Chapter Six 4 JHH = 1.2 Hz, ArH
Page 189 and 190: Time (minutes) 4 11 18 25 Table 6.2
Page 191 and 192: Time (minutes) 19 F{ 1 H} (ppm) Tim
Page 193 and 194: 175 Chapter Six suspension of sodiu
Page 195 and 196: 177 Chapter Six Hz, Ha), 5.19 (1H,
Page 197 and 198: 6.4.9 Preparation of Dimethyl 2-(4-
Page 199 and 200: 181 Chapter Six 6.4.13 Preparation
Page 201 and 202: 6.5 Experimental Details for Chapte
Page 203 and 204: 185 Chapter Six CHCH2), 133.9 (d, 3
Page 205 and 206: 187 Chapter Six 6.5.6 Preparation o
Page 207 and 208: 189 Chapter Six (5 mg, 0.27 mmol) a
Page 209 and 210: 191 Chapter Six (d, 1 JCF = 255.0 H
Page 211 and 212: 193 Chapter Six layer separated and
Page 213 and 214: 195 Chapter Six Hz, 4 JHF = 3.2 Hz,
Page 219 and 220: Appendix
Page 221 and 222: II Appendix Second generation Grubb
Page 223 and 224: IV Appendix mixture was stirred at
Page 225 and 226: VI Appendix stirred at room tempera
Page 227 and 228: VIII Appendix The organic phase was
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X Appendix A6 Crystal data and stru
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XII Appendix A8 Crystal data and st
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XIV Appendix A10 Crystal data and s
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A12 Lecture Courses Attended XVI Ap
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A14 Conferences Attended RSC Organi
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