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

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Experimental for chapter 3.1 ν max (film)/cm -1 : 3030 (NH), 1602, 1496; 1 H-NMR (CDCl 3 , 300 MHz) δ 7.45-7.22 (m, 10H, H-Ar), 3.18 (s, 2H, CHPh), 1.50 (br, 1H, NH); 13 C-NMR (CDCl 3 , 75 MHz) δ 139.9 (ipso-Ph), 128.9, 127.6, 125.8 (Ph), 44.0 (CHPh). Synthesis of (1S, 2R)-2-amino-1,2-diphenylethanol (174) HO N 3 H 2 , Pd/C, HCl HO NH 2 Ph Ph Ph Ph By method of Sharpless 10 hydrochloric acid (0.56 cm 3 in 0.5 cm 3 water, 6.3 mmol) was added drop wise to a stirred solution of crude azide 178 (1.25 g, 5.23 mmol) and palladium on charcoal (10%, 60 mg) in EtOH (9 cm 3 ). The mixture was placed under atmospheric pressure of hydrogen, and stirred vigorously for 48 hr. Water (20 cm 3 ) was added and the mixture concentrated under vacuum before filtration and acid-base extraction into CH 2 Cl 2 (3 x 20 cm 3 ), dried over Na 2 SO 4 and solvent evaporated. Amino alcohol 174 (1.09 g, 97%) was isolated as clear colourless needles by recrystallisation from CH 2 Cl 2 . R f : 0.22 (19:1 EtOAc:MeOH); Mpt: 143-144 °C (CH 2 Cl 2 ), lit. 143-144 °C (no solvent stated) 10 ; [α] 22 D : +8.0 (c = 0.6, EtOH) lit. 10 for enantiomer –7.0 (c = 0.6, EtOH, no temp stated), MS m/z (CI+): 214 (100%, MH + ), 216 (6%, (M+1)H + ); IR ν max (film)/cm - 1 : 3064, 1604, 1595; 1 H-NMR (CDCl 3 , 500 MHz) δ 7.36-7.21 (m, 10H, Ph), 4.77 (d, 1H, J 6.5, CHOH), 4.19 (d, 1H, J 6.5, CHNH 2 ), 1.67 (br s, 3H, OH, NH 2 ); 13 C-NMR (CDCl 3 , 125 MHz) δ 141.5 (ipso-Ph), 140.5 (ipso-Ph), 128.5 (meta-Ph), 128.0 (meta- Ph), 127.7 (para-Ph), 127.6 (para-Ph), 127.1 (ortho-Ph), 126.6 (ortho-Ph), 78.3 (CHOH), 61.7 (CHNH 2 ). Synthesis of cis-stilbene oxide (179) O mCPBA Ph Ph Ph Ph mCPBA (1.58 g, 70% purity, 6.4 mmol) was added portion wise to a solution of cisstilbene (1.011 cm 3 , 5.3 mmol) in CH 2 Cl 2 (50 cm 3 ) and stirred for 6 hr, before addition of aqueous sodium sulfite (saturated, 10 cm 3 ). The solution was washed with saturated aqueous NaHCO 3 (2 x 50 cm 3 ), CH 2 Cl 2 (2 x 50 cm 3 ), EtOAc (50 cm 3 ), dried over 213
Experimental for chapter 3.1 Na 2 SO 4 and solvent evaporated. cis-Stilbene oxide (935 mg, 90%) was obtained as clear colourless needles after flash chromatography (20:1 to 4:1 petrol:EtOAc). R f : 0.35 (9:1 petrol:EtOAc); Mpt: 38 °C (CH 2 Cl 2 ), lit. 21 38-40 °C; MS m/z (CI+): 197 (100%, MH + ), 189 (9%, (M+1)H + ), 214 (MNH + 4 ,57%); IR ν max (film)/cm -1 : 3163, 2994, 1603, 1005; 1 H-NMR (CDCl 3 , 500 MHz) δ 7.72-7.16 (m, 10H, Ph), 4.40 (s, 2H, CH); 13 C-NMR (CDCl 3 , 125 MHz) δ 134.3 (ipso-Ph), 127.7, 127.5, 126.8 (Ph), 29.7 (CH). Synthesis of (R*,R*)-2-amino-1,2-diphenylethanol (175) Ph O Ph NH3 (aq.) HO Ph (±) NH 2 Ph Microwave: cis-Stilbene oxide (700 mg, 3.57 mmol) was fully dissolved in MeOH (2.5 cm 3 ) before addition of saturated aqueous ammonia (7.5 cm 3 ) caused a fine precipitate. The resulting solution was heated at 140 °C under microwave irradiation for 20 min (pressure peaked at 11 bar) giving a clear yellow solution, which upon standing overnight gave colourless cubes. Filtration and two further recrystallisations from diethyl ether gave racemic amino alcohol 175 (710 mg, 93%). Reflux: cis-Stilbene oxide (500 mg, 2.55 mmol) was dissolved in MeOH (19 cm 3 ) with saturated aqueous ammonia (19 cm 3 ) and brought to gentle reflux (c. 70 °C, raising to 80 °C) for 24 hr. The clear solution was concentrated under vacuum, transferred to a separatory funnel with aqueous NaOH (2 cm 3 NaOH 2N in 50 cm 3 water), washed with CH 2 Cl 2 (2 x 50 cm 3 ) and EtOAc (50 cm 3 ), dried over Na 2 SO 4 , and concentrated under vacuum to give a white solid. Purification by flash chromatography (1:1 petrol:EtOAc to 19:1 EtOAc:MeOH) isolated stilbene oxide (125 mg) and a white solid, which was recrystallised from CH 2 Cl 2 to give clear colourless cubic crystals of racemic amino alcohol 175 (295 mg, 55%). R f : 0.24 (19:1 EtOAc:MeOH); Mpt: 127-128 °C (CH 2 Cl 2 ), lit: 116-119 °C; MS m/z (CI+): 214 (39%, MH + ), 106 (100%, CHPhNH 2 + ); IR ν max (film)/cm -1 : 3066 (br, OH), 1604, 1595; 1 H-NMR (CDCl 3 , 300 MHz) δ 7.41-7.21 (m, 10H, Ph), 4.70 (d, 1H, J 6.5, 214
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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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Experimental for chapter 4.2 (1S*,2
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Experimental for chapter 4.2 310 R
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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 Synthe
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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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