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

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Experimental for chapter 3.1 R f : 0.52 (2:1 petrol:EtOAc); [α] 22 D : –40.8 (c = 1.5); MS m/z (CI+): 220 (100%, MH + ), 221 (10%, (M+1)H + ); HRMS (ESI+) m/z found 220.1330 (MH calcd. 220.1332); IR ν max (film)/cm -1 : 2961 (m, C–H), 1645 (C=N), 1610, 1512, 1258 (C–Me); 1 H-NMR (CDCl 3 , 500 MHz) δ 7.87 (d, 2H, J 9.0, H2), 6.88 (d, 2H, J, 9.0, H3), 4.39-4.29 (m, 1H, CH A H B ), 4.10-4.01 (m, 2H, CH A H B & CHN), 3.80 (s, 3H, OMe), 1.82 (oct, 1H, J 6.5, CHMe 2 ), 1.00 (d, 3H, J 7.0, CHMe A Me b ), 0.89 (d, 3H, J 7.0, CHMe a Me B ); 13 C- NMR (CDCl 3 , 125 MHz) δ 163.0 (C=O), 161.8 (C1, 129.8 (C2), 120.4 (C4), 113.5 (C3), 72.4 (CHN), 69.9 (OCH 2 ), 55.2 (OMe), 32.8 (CHMe 2 ), 18.9 (CHMe A Me b ), 18.0 (CHMe a Me B ); Synthesis of N-((1R,2S)-1-hydroxy-1-phenylpropan-2-yl)benzamide (166) Ph O Cl Ph Me NH 2 HO O Me NH OH Et 3 N 1 2 3 4 General procedure 3 was used mixing benzoyl chloride (0.32 cm 3 , 2.76 mmol), (–)- norepedrine (500 mg, 3.31 mmol) and triethylamine (10 cm 3 ) to give the amide 166 (700 mg, 99%) as clear colourless cubes. R f : 0.21 (2:1 petrol:EtOAc); Mpt: 164-165 °C (acetone); [α] 22 D : +32 (c = 0.2, EtOH); MS m/z (CI+): 256 (100%, MH + ) 257 (14%, (M+1)H + ); HRMS (ESI+) m/z found 256.1336 (MH + , calcd. 256.1332); IR ν max (film)/cm -1 : 3286 (OH), 1635 (C=N), 1543 (C–Me); 1 H-NMR (CDCl 3 , 300 MHz) δ 7.84-7.76 (m, 2H, H2), 7.60-7.32 (m, 8H, Ph), 6.33 (d, 1H, J 7.5, NH), 5.30 (d, 1H, J 3.0, CHPh), 4.60 (dqd, 1H, J 7.5, 7.0, 3.0 CHMe), 1.17 (d, 3H, J 7.0, Me); 13 C-NMR (CDCl 3 , 125 MHz) δ 168.5 (CO), 141.0 (ipso-Ph), 134.6 (ipso-Ph), 132.1, 129.1, 129.0, 128.7, 128.0, 127.4, 126.8, 126.8, 126.7 (Ph), 51.8 (CNH), 12.2 (Me). COH under solvent peak by HMQC. 233
Experimental for chapter 3.1 Synthesis of (4S,5S)-4-methyl-2,5-diphenyloxazoline (110) HO O Ph NH Me DIC, Cu(OTf) 2 Ph O Me N Δ General procedure 3 was used with benzamide (200 mg, 0.78 mmol), DIC (0.12 cm 3 , 0.78 mmol), Cu(OTf) 2 (18 mg, 0.05 mmol), THF (3 cm 3 ) and heated under microwave irradiation for 5 min at 150 °C. Flash chromatography (4:1 petrol:EtOAc) yielded an inseparable mixture of oxazoline 110 and its diastereomer (195 mg, 65%, 95:5) as colourless needles. R f : 0.59 (2:1 petrol:EtOAc); MS m/z (CI+): 238 (100%, MH + ), 239 (18%, (M+1)H + ), 131 (51%, [M-PhCHO] + ); HRMS (ESI+) m/z found 238.1224 (MH calcd. 238.1226); IR ν max (film)/cm -1 : 2926 (C-H), 1648 (C=N), 1450, 1269; 1 H-NMR data for major compound (CDCl 3 , 300 MHz) δ 8.07-8.00 (m, 2H, ortho-Ph), 7.54-7.25 (m, 8H, Ph), 5.11 (d, 1H, J 8.0, CHPh), 4.22 (quin, 1H, J 7.0, CHMe), 1.50 (d, 3H, J 6.5, Me); 13 C- NMR (75 MHz, CDCl 3 ) δ 164.2 (C=N), 140.2 (ipso-Ph), 131.7, 128.9, 128.8, 128.6, 128.4, 127.7 (Ph) 127.4 (ipso-Ph), 126.7, 125.7 (Ph), 86.2 (CHOPh), 63.3 (CHNMe), 22.7 (Me). 234
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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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3.1 - Oxazoline synthesis 3.1.1.a H
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3.1 - Oxazoline synthesis O Ar OH i
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3.1 - Oxazoline synthesis 3.1.2 Gen
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3.1 - Oxazoline synthesis mCPBA O N
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3.1 - Oxazoline synthesis 3.1.4.b M
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3.1 - Oxazoline synthesis Ph Ph Ph
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3.2 - Oxazoline removal O N O OH 3N
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3.2 - Oxazoline removal O Me O N OM
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3.2 - Oxazoline removal However, th
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3.2 - Oxazoline removal 3.2.3 Reduc
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3.2 - Oxazoline removal Ph O N Ph P
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3.2 - Oxazoline removal 3.2.3.c Ami
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3.2 - Oxazoline removal Ph Ph Ph Ph
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3.2 - Oxazoline removal 3.2.5.b N-A
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3.2 - Oxazoline removal Ph Ph O N H
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3.2 - Oxazoline removal Ph Me Ph Me
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3.2 - Oxazoline removal 3.2.6 Deter
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Better, however, would be a method
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4.1 - Introduction HO OH OH HO OH O
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4.1 - Introduction (-)-Shikimic aci
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4.1 - Introduction followed by Flem
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4.2 - Carbasugar synthesis 4.2 Synt
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4.2 - Carbasugar synthesis stereoce
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4.2 - Carbasugar synthesis of the o
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4.2 - Carbasugar synthesis support
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4.2 - Carbasugar synthesis Ox* Ox*
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4.2 - Carbasugar synthesis OsO 4 (c
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4.2 - Carbasugar synthesis taken on
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4.2 - Carbasugar synthesis As well
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4.4 - Revised altrose synthesis 4.4
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4.4 - Revised altrose synthesis suf
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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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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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