162 Chapter Six (50:50)] afforded <strong>the</strong> product as an oil (0.19 g, 34 %). δH 4.51 (1H, dd, 2 JHH = 11.3 Hz, 3 JHH = 7.0 Hz, Hd), 4.55 (1H, dd, 2 JHH = 11.3 Hz, 3 JHH = 5.9 Hz, He), 4.67-4.73 (1H, m, CHCl), 5.34 (1H, d, 3 JHH = 10.2 Hz, Hb), 5.48 (1H, ap.dt, 3 JHH = 16.8 Hz, 2 JHH = 4 JHH = 0.8 Hz, Ha), 5.98 (1H, ddd, 3 JHH = 16.8 Hz, 3 JHH = 10.2 Hz, 3 JHH = 7.8 Hz, Hc), 7.30 (1H, ap.tdd, 3 JHH = 3 JHF = 8.6 Hz, 4 JHH = 2.7 Hz, 4 JHH = 1.2 Hz, ArH-4), 7.46 (1H, td, 3 JHH = 8.2 Hz, 4 JHF = 5.5 Hz, ArH-5), 7.75 (1H, ddd, 3 JHF = 9.4 Hz, 4 JHH = 2.7 Hz, 4 JHH = 1.6 Hz, ArH-2), 7.87 (1H, dt, 3 JHH = 7.8 Hz, 4 JHH = 1.2 Hz, ArH-6); δC 58.6 (CHCl), 67.4 (OCH2), 116.7 (d, 2 JCF = 22.6 Hz, ArCH-2), 119.6 (CHCH2), 120.4 (d, 2 JCF = 21.4 Hz, ArCH-4), 125.5 (d, 4 JCF = 2.5 Hz, ArCH-6), 130.2 (d, 3 JCF = 8.8 Hz, ArCH-5), 131.8 (d, 3 JCF = 7.5 Hz, ArC-1), 134.3 (CHCH2), 162.6 (d, 1 JCF = 246.5 Hz, ArCF), 164.9 (d, 4 JCF = 3.8 Hz, C=O); δF –112.1. m/z (EI + ) 228 ([M] + , 33 %) 123 ([M-OCH2CHClCH=CH2] + , 90 %). HRMS (EI) 228.03509 (C11H10O2ClF requires 228.03509). 6.2.39 Preparation <strong>of</strong> 2-chlorobut-3-enyl 2-fluorobenzoate (111) The novel compound was prepared following <strong>the</strong> method outlined by Munyemana et al. [11] A 100 cm 3 , three-necked round-bottom flask was equipped with a magnetic stirring bar <strong>and</strong> Rotaflo tap <strong>and</strong> attached to a Schlenk line. After flame-drying under high vacuum, <strong>the</strong> flask was cooled <strong>and</strong> filled with nitrogen. The reaction flask was <strong>the</strong>n charged with 2-hydroxybut-3-enyl 2-fluorobenzoate (0.30 g, 1.43 mmol) <strong>and</strong> anhydrous DCM (15 cm 3 ). The flask was <strong>the</strong>n cooled to 0 ºC using an ice bath. Once cooled tetramethyl-�-chloroenamine was added (0.19 cm 3 , 1.43 mmol) via syringe. The reaction mixture was <strong>the</strong>n stirred at room temperature for 3 h. After which purification by chromatography [DCM: cyclohexane (50:50)] afforded <strong>the</strong> product as an oil (0.15 g, 47 %). δH 4.43 (1H, dd, 2 JHH = 11.7 Hz, 3 JHH = 7.0 Hz, Hd), 4.47(1H, dd, 2 JHH = 11.7 Hz, 3 JHH = 5.9 Hz, He), 4.58-4.64 (1H, m, CHCl), 5.24 (1H, d, 3 JHH = 10.2 Hz, Hb), 5.39 (1H, ap.dt, 3 JHH = 16.8 Hz, 2 JHH = 4 JHH = 0.8 Hz, Ha), 5.90 (1H, ddd, 3 JHH = 16.8 Hz, 3 JHH = 10.2 Hz, 3 JHH = 7.8 Hz, Hc), 7.08 (1H, ddd, 3 JHF = 11.0 Hz, 4 JHH = 8.2 Hz, 5 JHH = 1.2 Hz, ArH-3), 7.15 (1H, td, 3 JHH = 7.8 Hz, 4 JHH = 1.2 Hz, ArH-5), 7.47 (1H dddd, 3 JHH = 8.2 Hz, 3 JHH = 7.4 Hz, 4 JHF = 4.7 Hz, 4 JHH = 2.0 Hz,, ArH-4), 7.88 (1H, td, 3 JHH = 4 JHF = 7.4 Hz, 4 JHH = 2.0 Hz, ArH-6); δC 57.6 (CHCl), 66.3 (OCH2), 116.0 (d, 2 JCF = 22.1 Hz, ArCH-3), 117.1 (d, 2 JCF = 9.1 Hz, ArC-1), 118.4 (CHCH2), 123.0 (d, 4 JCF = 5.0 Hz, ArCH-5), 131.1 (ArCH-6), 133.4 (CHCH2), 133.8 (d, 3 JCF = 9.1 Hz, ArCH-4), 161.1 (d, 1 JCF = 261.6 Hz, ArCF), 162.7 (C=O); δF -109.0 (1F, s, CF). m/z (EI + ) 228 ([M] + , 23 %) 123 ([M- OCH2CHClCH=CH2] + , 100 %). HRMS (EI) 228.03507 (C11H10O2ClF requires 228.03509).
6.2.40 Preparation <strong>of</strong> 2-chlorobut-3-enyl 4-(methyl)benzoate (113) 163 Chapter Six The novel compound was prepared following <strong>the</strong> method outlined by Munyemana et al. [11] A 100 cm 3 , three-necked round-bottom flask was equipped with a magnetic stirring bar <strong>and</strong> Rotaflo tap <strong>and</strong> attached to a Schlenk line. After flame-drying under high vacuum, <strong>the</strong> flask was cooled <strong>and</strong> filled with nitrogen. The reaction flask was <strong>the</strong>n charged with 2- hydroxybut-3-enyl 4-methylbenzoate (1.19 g, 5.80 mmol) <strong>and</strong> anhydrous DCM (5 cm 3 ). The flask was <strong>the</strong>n cooled to 0 ºC using an ice bath. Once cooled tetramethyl-�- chloroenamine was added (0.77 cm 3 , 5.80 mmol) via syringe. The reaction mixture was <strong>the</strong>n stirred at room temperature for 3 h. After which purification by chromatography [DCM: cyclohexane (50: 50)] afforded <strong>the</strong> product as an oil (0.41 g, 32 %). δH 2.44 (3H, s, CH3), 4.49 (1H, dd, 2 JHH = 11.3 Hz, 3 JHH = 7.0 Hz, Hd), 4.54 (1H, dd, 2 JHH = 11.3 Hz, 3 JHH = 5.9 Hz, He), 4.67-4.73 (1H, m, CHCl), 5.32 (1H, d, 3 JHH = 10.2 Hz, Hb), 5.47 (1H, ap.dt, 3 JHH = 16.8 Hz, 2 JHH = 4 JHH = 1.2 Hz, Ha), 5.98 (1H, ddd, 3 JHH = 16.8 Hz, 3 JHH = 10.2 Hz, 3 JHH = 7.8 Hz, Hc), 7.27 (2H, d, 3 JHH = 8.6 Hz, ArH-3), 7.96 (1H, dm, 3 JHH = 8.6 Hz, ArH-2); δC 21.7 (CH3), 58.8 (CHCl), 66.9 (OCH2), 119.3 (CHCH2), 126.9 (ArC-1), 129.2 (ArCH-3), 129.8 (ArCH-2), 134.6 (CHCH2), 144.0 (ArC-4), 166.0 (C=O). m/z (EI + ) 224 ([M] + , 32 %) 119 ([M-OCH2CHClCH=CH2] + , 100 %). HRMS (EI) 224.06006 (C12H13O2Cl requires 224.06008). 6.2.41 Preparation <strong>of</strong> 2-chlorobut-3-enyl 4-(trifluoromethyl)benzoate (112) The novel compound was prepared following <strong>the</strong> method outlined by Munyemana et al. [11] A 100 cm 3 , three-necked round-bottom flask was equipped with a magnetic stirring bar <strong>and</strong> Rotaflo tap <strong>and</strong> attached to a Schlenk line. After flame-drying under high vacuum, <strong>the</strong> flask was cooled <strong>and</strong> filled with nitrogen. The reaction flask was <strong>the</strong>n charged with 2- hydroxybut-3-enyl 4-(trifluoromethyl)benzoate (0.50 g, 1.93 mmol) <strong>and</strong> anhydrous DCM (25 cm 3 ). The flask was <strong>the</strong>n cooled to 0 ºC using an ice bath. Once cooled tetramethyl-�- chloroenamine was added (0.28 cm 3 , 2.13 mmol) via syringe. The reaction mixture was <strong>the</strong>n stirred at room temperature for 3 h. After which purification by chromatography [DCM: cyclohexane (50:50)] afforded <strong>the</strong> product as an oil (0.20 g, 37 %). δH 4.45 (1H, dd, 2 JHH =
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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
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111 Chapter Four were both reacted
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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