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

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Experimental for chapter 3.1 Synthesis of N-((1R,2S)-2-hydroxy-1,2-diphenylethyl)-2-methoxybenzamide (165i) Ph O Cl OMe Ph Ph NH 2 OH Et 3 N HO O 1 6 5 Ph NH OMe 2 3 4 General procedure 1 was used mixing o-anisoyl chloride (0.38 cm 3 , 2.54 mmol) with the amino alcohol yy (600 mg, 2.80 mmol) and triethylamine (0.71 cm 3 ) to give the amide 165i (880 mg, 99%) as colourless needles. R f : 0.65 (EtOAc); Mpt: 172-3 °C (EtOAc); [α] 22 D : 100.7 (c = 0.6, EtOH); MS m/z (CI+): 348 (100%, MH + ), 349 (20%, (M+1)H + ), 330 (22%, [M-H 2 O]H + ); HRMS (ESI+) m/z found 348.1596 (MH calcd. 348.1594); IR ν max (film)/cm -1 : 3330, 1629 (C=O), 1527; 1 H-NMR (CDCl 3 , 500 MHz) δ 8.75 (d, 1H, J 7.5, NH), 8.21 (dd, 1H, J 8.0, 2.0, H6), 7.46 (ddd, 1H, J 8.0, 7.5, 2.0, H4), 7.28-7.21 (m, 6H, Ar), 7.10-7.02 (m, 5H, Ar), 7.0 (d, 1H, J 8.5, 5.65 (dd, 1H, J 4.0, 7.5, CHNH), 5.17 (d, 1H, J 4.0, CHOH), 3.91 (s, 3H, OMe); 13 C-NMR (CDCl 3 , 125 MHz) δ 165.6 (C=O), 157.6 (C1), 139.5 (ipso-Ph), 137.7 (ipso-Ph), 133.0, 132.4, 132.3, 128.2, 127.6, 127.5, 126.9, 126.7, 121.4, 121.2, 120.9, 111.2, 60.1 (COH), 56.0 (CNH). Synthesis of (4R,5R)-2,4,5-triphenyloxazoline (101a) HO O Ph NH Ph DIC, Cu(OTf) 2 Ph O N Ph Δ Reflux: General procedure 2 was used with benzamide (317 mg, 1.0 mmol), DIC (0.15 cm 3 , 1.0 mmol), Cu(OTf) 2 (22 mg, 0.06 mmol), dioxane (3 cm 3 ) and heated under reflux for 7 hr at 105 °C. Flash chromatography (19:1 petrol:EtOAc) yielded oxazoline 101a (195 mg, 65%) as colourless needles. 221
Experimental for chapter 3.1 Microwave: General procedure 2 was used with benzamide (160 mg, 0.50 mmol), DIC (0.08 cm 3 , 0.38 mmol), Cu(OTf) 2 (11 mg, 0.03 mmol), THF (3 cm 3 ) and heated under microwave irradiation for 20 min at 150 °C. Flash chromatography (19:1 petrol:EtOAc) yielded oxazoline 101a (86 mg, 58%) as colourless needles. R f : 0.51 (4:1 petrol:EtOAc); Mpt: 106-108 ºC (toluene) lit. 16 93-95 ºC; [α] 25 D : –11 (c = 3.0, EtOH); MS m/z (CI+): 300 (100%, MH + ), 301 (21%, (M+1)H + ), 193 (12%, [M- PhCO] + ); IR ν max (film)/cm -1 : 1650 (C=N), 1602, 1494, 1325; 1 H-NMR (300 MHz, CDCl 3 ) δ 8.17 (d, 2H, J 7.0, ortho-Ph), 7.60-7.27 (m, 13H, Ph), 5.44 (d, 1H, J 7.5, OCHPh), 5.26 (d, 1H, J 7.5, NCHPh); 13 C-NMR (75 MHz, CDCl 3 ) δ 164.0 (C=N), 141.9 (ipso-Ph), 140.4 (ipso-Ph), 131.7, 128.9, 128.8, 128.6, 128.4, 128.4, 127.7 (Ph) 127.4 (ipso-Ph), 126.7, 125.7 (Ph), 88.9 (COPh), 79.0 (CNPh); chiral HPLC: Pirkle Covalent (R,R) Whelk-O1 column, 10% IPA in hexane, 1 cm 3 min -1 , 100%, 6.7 min; racemic sample: 50% - 6.8 min, 50% - 10.5 min. Synthesis of (4R*, 5R*)-2,4,5-triphenyloxazoline (101a) and (4R*, 5R*)-2-(4- methoxyphenyl)-4,5-diphenyloxazoline (101b) O NH 2 Ph Ph O N Ph Ph O N O NH 2 i) (Et 3 O)BF 4 1 Ph ii) HO Ph 4 OMe H 2 N (±) OMe ±101a ±101b General procedure 3 was used mixing benzamide (67 mg, 0.55 mmol), para-anisamide (84 mg, 0.55 mmol) with the triethyloxonium salt (228 mg, 1.20 mmol) before addition of the α-amino alcohol (280 mg, 1.35 mmol). Purification by flash chromatography (9:1 petrol:EtOAc), and recrystallisation from toluene/hexane yielded oxazoline 101a (140 mg, 85%) as colourless needles and oxazoline 101b (155 mg, 86%) as colourless needles. 101a data as enantiopure (previous page) Chiral HPLC: Pirkle Covalent (R,R) Whelk- O1 column, 10% IPA in hexane, 1mL/ min: 50% - 6.8 min, 50% - 10.5 min. 2 3 222
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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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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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