A Route to Carbasugar Analogues - Jonathan Clayden - The ...

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Chapter 3 – Oxazoline synthesis & removal A similar transformation had previously been developed by Pridgen using diborane with non-aromatic substituents, giving amines 196. 138 However, unlike the Meyers reduction the substituents were simple hydrocarbons, and diborane will react with unsaturated groups. Ph O R N B 2 H 6 , THF Δ R H N 196 Ph OH 56-94% 3 examples (aliphatic) Scheme 3.21 – borane reduction of oxazoline 138 In the same publication, Pridgen reports the catalytic hydrogenolysis of the benzylic carbon-oxygen bond of oxazoline 197 to give secondary amide 198. This method is of particular interest since both carbon-heteroatom bonds in the diphenyl oxazoline are benzylic. O N Ph Pd/C, H 2 (50 psi) O N H Ph EtOH/HCl OMe OMe OMe OMe 197 198 98% Scheme 3.22 – hydrogenolysis of oxazoline C–O bond 138 3.2.2 General strategy The methods presented above generally involve two synthetic steps in good overall yield, but only a few permit the recovery of the amino alcohol. The most promising route appears to be the one-pot TFA-LiAlH 4 procedure which has been shown to proceed in good yield and does not appear to affect optical purity. Likewise, acid hydrolysis permits recovery of the amino alcohol, but has not been employed on many non-aromatic or chiral substrates. From its extensive use by Meyers, the method most likely to work is the two-pot alkylation-reduction-hydrolysis procedure which unmasks the oxazoline as an aldehyde, accompanied by the N-methyl amino alcohol. 111
3.2 – Oxazoline removal However, the diphenyl oxazoline lends itself to hydrogenolysis since both C–X bonds are benzylic, although the literature precedent for this reaction contained only the more labile C–O benzylic bond. Whilst it would not return the amino alcohol, the main advantage of this method is that it would involve a single reagent with very well understood reactivity with other functional groups. 3.2.2.a Model compounds Ph Ph Ph Ph O N O N 101m O 201 Scheme 3.23 – model oxazolines Whilst we are interested in cleaving 2-alkyloxazolines all oxazolines studied so far, and most of those found in the literature, are 2-aryloxazolines. 2-Cyclohexyloxazoline 101m and enone 201 will be used to study the removal of the oxazoline moiety. The former is a simple system which can be quickly synthesised, whilst the latter contains a challenging quaternary centre and functionality that will be encountered in a future synthesis. Enone 201 can readily be synthesised from diene 102b (Table 3.6). 112
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Dearomatising Addition of Organolit
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2.3 Synthetic Scope 64 2.3.1 Organo
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Abstract Dearomatising Addition of
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The Author The Author graduated fro
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Abbreviations & Conventions Ac acet
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RDS rate determining step R f RC rt
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Chapter 1: Introduction Chapter 1 -
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Chapter 1: Introduction controlled
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Chapter 1: Introduction diastereome
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Chapter 1: Introduction combine mor
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Chapter 1: Introduction O Ar Cl TMP
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Chapter 1: Introduction conditions,
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Chapter 1: Introduction chiral oxaz
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Chapter 1: Introduction Again a lar
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Chapter 1: Introduction 34 Scheme 1
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Chapter 1: Introduction The amino a
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Chapter 1: Introduction It was envi
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Chapter 1: Introduction COR' i) ATP
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Chapter 1: Introduction O i) ATPH,
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Chapter 1: Introduction 1.4 Nucleop
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Chapter 1: Introduction Unlike the
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Chapter 1: Introduction Diene (-)-8
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Chapter 1: Introduction A scheme su
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Chapter 1: Introduction Cl R + 93 S
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Chapter 2 - Dearomatising additions
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Page 60 and 61: Chapter 2 - Dearomatising additions
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Page 95 and 96: 3.1 - Oxazoline synthesis 3.1.1.a H
Page 97 and 98: 3.1 - Oxazoline synthesis O Ar OH i
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Page 101 and 102: 3.1 - Oxazoline synthesis mCPBA O N
Page 103 and 104: 3.1 - Oxazoline synthesis 3.1.4.b M
Page 105 and 106: 3.1 - Oxazoline synthesis Ph Ph Ph
Page 107 and 108: 3.2 - Oxazoline removal O N O OH 3N
Page 109: 3.2 - Oxazoline removal O Me O N OM
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Page 115 and 116: 3.2 - Oxazoline removal Ph O N Ph P
Page 117 and 118: 3.2 - Oxazoline removal 3.2.3.c Ami
Page 119 and 120: 3.2 - Oxazoline removal Ph Ph Ph Ph
Page 121 and 122: 3.2 - Oxazoline removal 3.2.5.b N-A
Page 123 and 124: 3.2 - Oxazoline removal Ph Ph O N H
Page 125 and 126: 3.2 - Oxazoline removal Ph Me Ph Me
Page 127 and 128: 3.2 - Oxazoline removal 3.2.6 Deter
Page 129 and 130: Better, however, would be a method
Page 131 and 132: 4.1 - Introduction HO OH OH HO OH O
Page 133 and 134: 4.1 - Introduction (-)-Shikimic aci
Page 135 and 136: 4.1 - Introduction followed by Flem
Page 137 and 138: 4.2 - Carbasugar synthesis 4.2 Synt
Page 139 and 140: 4.2 - Carbasugar synthesis stereoce
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Page 143 and 144: 4.2 - Carbasugar synthesis support
Page 145 and 146: 4.2 - Carbasugar synthesis Ox* Ox*
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Page 157 and 158: 4.4 - Revised altrose synthesis 4.4
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4.4 - Revised altrose synthesis ind
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4.5 - Mannose synthesis 4.5 Synthes
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4.5 - Mannose synthesis It is clear
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4.5 - Mannose synthesis considering
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4.5 - Mannose synthesis which would
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4.5 - Mannose synthesis One clear a
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4.5 - Mannose synthesis 4.5.2.b Epo
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4.5 - Mannose synthesis hydrolysis
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4.5 - Mannose synthesis The second
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4.6 - Summary 4.6 Summary & Future
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4.6 - Summary OH CDI, NH 2 OH.HCl,
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184
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References (37) Rawson, D. J.; Meye
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References (105) Gajewski, J. J.; B
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References (169) McCormick, J. P.;
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References 192
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Experimental section 254nm, dodecam
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Experimental section General Proced
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Experimental for chapter 2 Synthesi
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Experimental for chapter 2 (CDCl 3
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Experimental for chapter 2 3H, OMe
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Experimental for chapter 2 Ph), 139
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Experimental for chapter 2 H4), 5.2
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Experimental for chapter 2 108 R f
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Experimental for chapter 2 Synthesi
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Experimental for chapter 3.1 satura
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Experimental for chapter 3.1 Na 2 S
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Experimental for chapter 3.1 Synthe
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Experimental for chapter 3.1 128.9,
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Experimental for chapter 3.1 Microw
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Experimental for chapter 3.1 R f :
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Experimental for chapter 4.1 281 R
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Experimental for chapter 4.1 combin
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Experimental for chapter 4.1 3H, OB
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Experimental for chapter 4.2 (1S*,2
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Experimental for chapter 4.2 10.0,
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Experimental for chapter 4.2 cm 3 )
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Experimental for chapter 4.2 5.7 Re
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Absolute structure parameter 1.3(11
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_diffrn_standards_interval_time ? _
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H13 H 0.8405 0.7136 -0.0889 0.026 U
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C4 C5 1.454(2) . ? C5 C6 1.324(2) .
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C24 C23 C22 120.0(2) . . ? C24 C23
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. Compound 102c Ph O N Ph Me 102c O
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_diffrn_standards_interval_time ? _
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H11 H 0.8924 0.9592 0.6829 0.022 Ui
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C2 H2 1.0000 . ? C3 C21 1.506(2) .
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C26 C21 C3 121.41(15) . . ? C23 C22
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c. Compound 213 Ph O N Ph Me OH 213
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_cell_volume 1080.9(4) _cell_formul
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_refine_ls_number_reflns 4736 _refi
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H25 H 0.7979 0.2335 0.3365 0.028 Ui
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C4 0.025(4) 0.019(4) 0.018(4) 0.001
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loop_ _geom_bond_atom_site_label_1
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C9 C4 C1 107.1(5) . . ? C10 C4 C1 1
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C36 C38 H38A 109.5 . . ? C36 C38 H3
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C29 C30 C36 C37 -90.4(7) . . . . ?
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The structure was solved by the dir
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_reflns_number_total 2447 _reflns_n
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C7 C 1.1671(4) 0.7629(7) 1.2254(4)
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C3 0.015(3) 0.016(3) 0.021(3) -0.00
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C21 H21A 0.9800 . ? C21 H21B 0.9800
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H21A C21 H21C 109.5 . . ? H21B C21
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