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

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56 Chapter Two purified using column chromatography [hexane: diethyl ether (95:5)], however, the product was obtained as a mixture with the starting material. Therefore, the reaction was repeated on a 2 mmol scale, after 48 hours the reaction had reached 65 % conversion. The reaction mixture was then purified via column chromatography [hexane: 100] followed by [hexane: diethyl ether (95:5)], however, no pure product could be isolated. The reaction of dimethylallyl benzoate (86) with allyltrimethylsilane proceeded in a similar manner, after 48 hours there was only 33 % conversion, therefore the reaction mixture was refluxed for an additional 48 hours, however, there was no improvement of the conversion. Purification of the mixture was attempted by column chromatography [hexane: diethyl ether (97:3)], however, no desired product was recovered only unwanted starting material. Hence, the reactions of methyl and dimethylallyl benzoate proved unsuccessful in affording the corresponding silyl products. This could be attributable to the methyl substituents hindering the metathesis mechanism. 2.2.1.3 Synthesis of Silyl Derivatised Allyl Benzoates Once all the derivatised allyl benzoates had been synthesised they were reacted with 3 equivalents of allyltrimethylsilane and 5 mol % 2 nd generation Grubbs catalyst in DCM, as previously described (Scheme 2.20). The yields obtained range from low to very good (34- 83 %) (Table 2.12). Both the 4-fluoro (81) and 3-fluoro benzoates (82) exhibited good conversion to (88) and (89) in the crude 1 H NMR spectra, 91 % and 77 % respectively, after 48 hours. Both reactions were then worked up by removing the solvent in vacuo and purifying by column chromatography [hexane (100)] followed by [hexane: diethyl ether (96:4)]. However, despite the fact that very small fractions were collected both the product and unreacted starting material came out together. The unreacted starting material does not affect the fluorination step, therefore most of the product: starting material mixture was used for the next synthetic step, whilst a small amount was retained so that it could be purified fully in order for full characterisation to be conducted. After testing several solvent systems, it was found that chloroform: hexane (70:30) could be used to successfully separate the desired product from the starting material. This solvent system was then also used to separate (89) from starting material, affording the product in 71 % yield. Allyl 2-fluorobenzoate (83) was converted to the corresponding silyl product (90) in 77 % yield after 48 hours. The product mixture was purified in the same way affording the silyl product in a 56 % isolated yield.
57 Chapter Two The conversion of (84) and (85) to product was a little lower (53 and 66 %), and they were only isolated as oils following column chromatography [chloroform: hexane (70:30)] in 35 and 34 % yields respectively ((91) and (92)). All products were fully characterised by 1 H, 13 C and 19 F NMR spectroscopy and mass spectrometry. Scheme 2.20 General reaction scheme for synthesis of silyl derivatised allyl benzoates Starting substrate Product Yield (%) (81) (82) (83) (84) (85) (88) (89) (90) (91) (92) Table 2.12 Yields of (88)-(92) 83 71 56 35 34
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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
Page 19 and 20: 6 Chapter One 2,10 (3,3-dichlorocam
Page 21 and 22: 8 Chapter One both enantiomers were
Page 23 and 24: 10 Chapter One poor to moderate ena
Page 25 and 26: Scheme 1.10 Fluorination of (17) 12
Page 27 and 28: 14 Chapter One fluorine donors, Lew
Page 29 and 30: 1.3 Enantioselective Nucleophilic F
Page 31 and 32: Scheme 1.16 Fluorination of (32) 18
Page 33 and 34: 20 Chapter One (iii) SN2’ type su
Page 35 and 36: 22 Chapter One cytotoxicity in the
Page 37 and 38: 24 Chapter One Manabe and Ishikawa
Page 39 and 40: Scheme 1.25 Synthesis of (41)-(44)
Page 41 and 42: Figure 1.12 �-fluorinated NSAIDs
Page 43 and 44: 1.6 Thesis Outline 30 Chapter One T
Page 45 and 46: 32 Chapter One [26] M. Abdul-Ghani,
Page 47 and 48: [79] M. Schlosser, D. Michael, Z.-W
Page 49 and 50: 2.1 Introduction 2 Synthesis of All
Page 51 and 52: 37 Chapter Two In dehydroxyfluorina
Page 53 and 54: Scheme 2.6 Fluorination with IF5/Et
Page 55 and 56: 41 Chapter Two desired allylic fluo
Page 57 and 58: 43 Chapter Two c) Formation of a su
Page 59 and 60: Scheme 2.14 Reaction of cis-3-methy
Page 61 and 62: Substrate (60) (61) (62) (63) R = O
Page 63 and 64: Alcohol Product Yield (%) Table 2.7
Page 65 and 66: 51 Chapter Two completion. This ena
Page 67 and 68: 53 Chapter Two Chapter Three. Follo
Page 69: 55 Chapter Two Two allyl alcohols w
Page 73 and 74: Starting substrate (88) (89) (90) (
Page 75 and 76: Starting substrate (99) (76) (77) (
Page 77 and 78: 63 Chapter Two Both (105) and (104)
Page 79 and 80: Scheme 2.25 Mechanistic pathway for
Page 81 and 82: 2.3 Conclusions 67 Chapter Two The
Page 83 and 84: [28] D. F. Taber, J. Am. Chem. Soc.
Page 85 and 86: Chapter THRee
Page 87 and 88: 72 Chapter Three Kurosawa reacted a
Page 89 and 90: 74 Chapter Three These results demo
Page 91 and 92: 76 Chapter Three More recently, wor
Page 93 and 94: 3.2 Results and Discussion 3.2.1 Re
Page 95 and 96: 80 Chapter Three Starting substrate
Page 97 and 98: 82 Chapter Three Figure 3.4 Crystal
Page 99 and 100: Scheme 3.12 Oxidative addition of 1
Page 101 and 102: 86 Chapter Three when the reaction
Page 103 and 104: 88 Chapter Three Therefore, from th
Page 105 and 106: -140 -140 -140 -140 -140 -150 -150
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
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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-
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157 Chapter Six 1 JCF = 253.5 Hz, A
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159 Chapter Six drying under high v
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6.2.37 Preparation of 2-chlorobut-3
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6.2.40 Preparation of 2-chlorobut-3
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6.3.2 Preparation of Bis[�-chloro
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167 Chapter Six 6.3.5 Preparation o
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169 Chapter Six 4 JHH = 1.2 Hz, ArH
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Time (minutes) 4 11 18 25 Table 6.2
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Time (minutes) 19 F{ 1 H} (ppm) Tim
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175 Chapter Six suspension of sodiu
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177 Chapter Six Hz, Ha), 5.19 (1H,
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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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