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

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Attempted preparation of 3,3-difluoro-2-phenylpent-4-en-2-ol VII Appendix The title compound was prepared using a method outlined by Burton et al. A 100 mL, three-necked round-bottomed flask was equipped with a magnetic stirring bar, Rotaflo tap and dropping funnel were attached to a Schlenk line. After flame-drying under high vacuum, the flask was cooled and filled with nitrogen. Acetophenone (0.35 cm 3 , 2.95 mmol) and anhydrous THF (10 mL) were added to the reaction flask containing acid washed zinc powder (0.39 g, 5.90 mmol). The reaction mixture was then cooled to 0 ºC and 3-bromo-3,3-difluoroprop-1-ene (0.3 cm 3 , 2.95 mmol) in THF (10 mL) was added dropwise over 30 minutes. After which the reaction mixture was warmed to room temperature and stirred overnight. A small aliquot was removed and quenched by the addition of aqueous 5 % HCl extracted with diethyl ether (10 cm 3 ), washed with saturated NaHCO3 and dried over magnesium sulphate. Analysis by 1 H NMR revealed only a small proportion of product to be present. Therefore the reaction mixture was heated at 45 ºC for 24 h. After which a small aliquot was then removed and worked up, however, analysis by 1 H NMR showed no further improvement in conversion to product, therefore, the reaction mixture was refluxed for 24 h and then sonicated for a further 24 h. After which the reaction mixture underwent work up and the crude product was analysed by 1 H NMR, however, the proportion of product was too small to purify by column chromatography. Reaction of 2,2-difluorobut-3-enyl benzoate with Pd(PPh3)4 A 50 cm 3 , two-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. Pd(PPh3)4 (l equiv.), and anhydrous CDCl3 were added to the reaction flask in a dry box. Subsequently, the flask was reattached to the Schlenk line, filled with nitrogen and charged with 2,2-difluorobut-3-enyl benzoate (1 equiv.), after stirring the reaction for 5 minutes a small aliquot was transferred to an NMR tube, and the reaction was monitored by 1 H and 19 F NMR spectroscopy and mass spectrometry. However, no desired product was observed only starting material. Reaction of 3-bromo-3,3-difluoroprop-1-ene with Pd(dba)2 in CDCl3 A 50 cm 3 , two-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. Pd(dba)2 (l equiv.), PPh3 (2 equiv.) and anhydrous CDCl3 were added to the reaction flask in a dry box. Subsequently, the flask was reattached to the Schlenk line, filled with nitrogen and charged with 3-bromo-3,3-difluoroprop-1-ene (2 equiv.), after stirring the reaction for 5 minutes a small aliquot was transferred to an NMR tube, and the reaction was monitored by 1 H and 19 F NMR spectroscopy and mass spectrometry. However no desired product was formed. Reaction of 3-bromo-3,3-difluoroprop-1-ene with Pd(dba)2 in DMSO A 50 cm 3 , two-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. Pd(dba)2 (1 equiv) was added to the reaction flask in a dry box. Subsequently, the flask was reattached to the Schlenk line, filled with nitrogen and charged with 3-bromo-3,3-difluoroprop-1-ene (1 equiv) and DMSO (10 cm 3 ). The reaction mixture was stirred for 2 h and then quenched with water (10 cm 3 ) and chloroform (10 cm 3 ).
VIII Appendix The organic phase was separated, washed with water (3 x 20 cm 3 ), dried over MgSO4 and concentrated in vacuo to give a yellow solid. However 1 H and 19 F NMR spectroscopy revealed no desired product to be present. Reaction of 3-bromo-3,3-difluoroprop-1-ene with Pd(PPh3)4 A 50 cm 3 , two-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. Pd(PPh3)4 (l equiv.), and anhydrous CDCl3 were added to the reaction flask in a dry box. Subsequently, the flask was reattached to the Schlenk line, filled with nitrogen and charged with 3-bromo-3,3-difluoroprop-1-ene (1 equiv.), after stirring the reaction for 5 minutes a small aliquot was transferred to an NMR tube, and the reaction was monitored by 1 H and 19 F NMR spectroscopy and mass spectrometry. The desired Pd cationic complex was observed by mass spectrometry, however, the main product formed was 3,3-difluoroallyltriphenylphosphonium bromide.
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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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[28] D. Landini, A. Maia, A. Rampol
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5.1 Introduction 5 Synthesis and Re
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116 Chapter Five The first enantios
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118 Chapter Five Gem(difluoroallyl)
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120 Chapter Five benzaldehyde, 3-br
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Starting Substrate (76) (77) (78) (
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Starting Substrate Product Yield (%
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5.2.4 Synthesis of Allylic Difluori
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5.2.5 Metal-mediated synthesis of 3
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130 Chapter Five process. [40] Unfo
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132 Chapter Five compounds were pur
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134 Chapter Five [30] H. L. Sham, N
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6.1 General Experimental Procedures
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6.2 Experimental Details for Chapte
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139 Chapter Six (1 g, 0.75 cm 3 , 6
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6.2.7 Preparation of allyl 4-(trifl
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6.2.10 Preparation of (3-[1,3]Dioxa
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145 Chapter Six reaction mixture wa
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147 Chapter Six mg, 1.1 mmol), ally
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149 Chapter Six 260.3 Hz, ArCF), 16
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6.2.22 Preparation of 2-fluorobut-3
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6.2.25 Preparation of 2-fluorobut-3
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6.2.28 Preparation of 2-hydroxybut-
Page 175 and 176: 157 Chapter Six 1 JCF = 253.5 Hz, A
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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
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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
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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
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Page 219 and 220: Appendix
Page 221 and 222: II Appendix Second generation Grubb
Page 223 and 224: IV Appendix mixture was stirred at
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Page 229 and 230: X Appendix A6 Crystal data and stru
Page 231 and 232: XII Appendix A8 Crystal data and st
Page 233 and 234: XIV Appendix A10 Crystal data and s
Page 235 and 236: A12 Lecture Courses Attended XVI Ap
Page 237 and 238: A14 Conferences Attended RSC Organi
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