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

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Figure 5.2 Cationic intermediate species formed 131 Chapter Five When the reaction was repeated with 50 mol % Pd(dba)2 and PPh3 (1 equivalent), the expected product, 3,3-difluoroallyltriphenylphosphonium bromide (182) was formed, however, the staring material was not fully consumed. Figure 5.3 Mass Spectra of cationic intermediate, observed (a) and predicted (b) 5.3 Conclusions Following Kirihara’s protocol 2,2-difluoro-1-phenylbut-3-en-1-ol (158) was successfully synthesised in 99 % yield, it was then utilised by reacting with derivatised benzoyl chlorides to synthesise a series of novel difluoroesters (159), (160), (161), (162), (163) and (164). All (a) (b)
132 Chapter Five compounds were purified successfully by column chromatography. Their structures were determined by NMR spectroscopy and mass spectrometry. A series of novel derivatised difluoro phenyl alcohols (166), (167), (168) and (169), were synthesised by reacting derivatised benzaldehydes with 3-bromo-3,3-difluoropropene in the presence of indium. These were then reacted further with 4-fluorobenzoyl chloride to form the corresponding difluoroesters (170), (171), (173) and (173). The novel allylic difluorides (175), (176), (177), (178) and (180) were synthesised by reaction of 2,2-difluorobut-3-en-1-ol in DCM solution with derivatised benzoyl chlorides. Attempts to activate these difluoroallyls with Pd(0) were unsuccessful, whilst the intermediate formed by the reaction of 3-bromo-3,3- difluoropropene with Pd(PPh3)4 was so reactive, almost instantaneous decomposition to a known phosphonium salt occurred. (168) R= 4-F (166) R= CF3 (167) R= CH3 (169) R= (2,3,4,5,6)-F (159) R= H (160) R= H (161) R= H (162) R= H (163) R= H (164) R= H (170) R= CH3 (172) R= 4-F (171) R= CF3 (173) R= (2,3,4,5,6)-F R’= H R’= 4-F R’= 3-F R’= 2-F R’= CF3 R’= CH3 R’= 4-F R’= 4-F R’= 4-F R’= 4-F (175) R= H (176) R= 4-F (177) R= 3-F (178) R= 2-F (180) R= CH3 Figure 5.4 Novel compounds synthesised in Chapter Five
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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
Page 97 and 98: 82 Chapter Three Figure 3.4 Crystal
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Page 101 and 102: 86 Chapter Three when the reaction
Page 103 and 104: 88 Chapter Three Therefore, from th
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Page 107 and 108: 92 Chapter Three monitored for 80 m
Page 109 and 110: 3.4 References [1] W. T. Dent, R. L
Page 111 and 112: Chapter Four
Page 113 and 114: 97 Chapter Four nucleophilic substi
Page 115 and 116: 99 Chapter Four Further reactions w
Page 117 and 118: Figure 4.3 Structure of co-product
Page 119 and 120: 4.2.2 Reactions of palladium cation
Page 121 and 122: 105 Chapter Four substituents on th
Page 123 and 124: 107 Chapter Four The desired produc
Page 125 and 126: 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
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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 and 178: 159 Chapter Six drying under high v
Page 179 and 180: 6.2.37 Preparation of 2-chlorobut-3
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-
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181 Chapter Six 6.4.13 Preparation
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6.5 Experimental Details for Chapte
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185 Chapter Six CHCH2), 133.9 (d, 3
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187 Chapter Six 6.5.6 Preparation o
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189 Chapter Six (5 mg, 0.27 mmol) a
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191 Chapter Six (d, 1 JCF = 255.0 H
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193 Chapter Six layer separated and
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195 Chapter Six Hz, 4 JHF = 3.2 Hz,
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Appendix
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II Appendix Second generation Grubb
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IV Appendix mixture was stirred at
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VI Appendix stirred at room tempera
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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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