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

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Experimental for chapter 3.1 R f : 0.41 (4:1 petrol:EtOAc); Mpt: 121-122 °C (EtOAc), 118-120 °C (PhMe); MS m/z (CI+): 345 (100%, MH + ), 346 (20%, (M+1)H + ), 238 (6%); HRMS (ESI+) m/z found 345.1237 (MH calcd. 345.1234); IR ν max (film)/cm -1 : 1648 (C=N), 1598, 1527, 1494 (NO 2 ), 1347 (NO 2 ); 1 H-NMR (CDCl 3 , 300 MHz) δ 8.32 (d, 2H, J 3.0, H2), 8.30 (d, 2H, J 3.0, H3), 7.44-7.33 (m, 8H, Ar), 7.31 (d, 1H, J 2.0, ortho-Ph), 7.28 (t, 1H, J 1.5, para-Ph), 5.49 (d, 1H, J 8.0, HCO), 5.30 (d, 1H, J 8.0, HCN); 13 C-NMR (CDCl 3 , 75 MHz) δ 162.1 (C=N), 149.7 (C4), 141.1 (ipso-Ph), 139.6 (ipso-Ph), 133.2 (C1), 129.6, 129.0, 129.0, 128.9 (Ph), 128.7 (para-Ph), 128.0 (para-Ph), 126.6, 125.7 (Ph), 123.6 (Ph), 89.6 (CHO), 79.0 (CHN). Synthesis of (4R,5R)-2-(2-methoxyphenyl)-4,5-diphenyloxazoline (101i) HO O Ph NH Ph DIC, Cu(OTf) 2 Ph O N Ph OMe Δ 1 6 5 4 2 3 OMe General procedure 2 was used with benzamide (890 mg, 2.56 mmol), DIC (0.40 cm 3 , 2.56 mmol), Cu(OTf) 2 (56 mg, 0.15 mmol), dioxane (9 cm 3 ) and heated under reflux for 18 hr at 120 °C. Flash chromatography (4:1 petrol:EtOAc) yielded oxazoline 101i (420 mg, 50%) as colourless needles. R f : 0.36 (3:1 petrol:EtOAc); Mpt: 79-81 °C (PhMe); [α] 21 D : –13 (c = 0.3, EtOH); MS m/z (CI+): 330 (100%, MH + ), 331 (23%, (M+1)H + ), 223 (14%, [M-PhCHO]H + ); HRMS (ESI+) m/z found 330.1488 (MH calcd. 330.1489); IR ν max (film)/cm -1 : 1654 (C=O), 1595, 1060; 1 H-NMR (CDCl 3 , 300 MHz) δ 7.95 (dd, 1H, J 8.0, 2.0, H6), 7.49 (td, 1H, J 8.5, 2.0, H4), 7.44-7.39 (m, 5H, Ph), 7.39-7.36 (m, 3H, Ph), 7.35-731 (m, 2H, Ph), 7.08-7.01 (m, 2H, H3, H5), 5.40 (d, 1H, J 7.0, CHO), 5.28 (d, 1H, J 7.0, CHN), 3.95 (s, 3H, OMe); 13 C-NMR (CDCl 3 , 75 MHz) δ 162.9 (C=N), 158.7 (C2), 142.2 (ipso-Ph), 140.7 (ipso-Ph), 132.4 (C4), 131.3 (C6), 128.7, 128.6, 128.1, 127.5, 126.6, 125.5 (Ar), 120.2 (C5), 116.9 (C1), 111.7 (C3), 88.1 (CHO), 79.0 (CHN), 55.9 (OMe). 227
Experimental for chapter 3.1 Synthesis of (4R,5R)-2-(3-hydroxylphenyl)-4,5-diphenyloxazoline (101k) & (4R,5R)-2-(3-(allyloxy)phenyl)-4,5-diphenyloxazoline (101j) Ph Ph Ph Ph O OH OH HN Ph Ph EDC.HCl SiO 2 , CH 2 Cl 2 rt, 30 hr O N OH AllylBr, K 2 CO 3 DMF, NaI O 1 6 5 4 N 2 3 O 101k 101j EDC.HCl (382 mg, 2 mmol) was added to a stirred solution of aziridine (195 mg, 1 mmol), silica (2 g) and 3-hydroxybenzoic acid (207 mg, 1.5 mmol) in CH 2 Cl 2 (10 cm 3 ). The solvent was removed after 32 hr and the resulting residue partitioned between water (10 cm 3 ) and CH 2 Cl 2 (30 cm 3 ). The aqueous phase was washed with further CH 2 Cl 2 (3 x 30 cm 3 ) and the combined organic phases dried over sodium sulphate, before purification by flash chromatography (4:1 petrol:EtOAc) to give phenol 101k (180 mg, 57%) and starting materials (20%). Adapted from the method of Ishizaki, 17 allyl bromide (83 µl, 0.95 mmol) was added to a solution of phenol 101k (200 mg, 0.63 mmol), sodium iodide (9 mg, 0.06 mmol), potassium carbonate (173 mg, 1.26 mmol) in DMF (7 cm3) and stirred for 16 hr. Water (2 cm 3 , mild exotherm) was added and air blown of the stirred reaction mixture for a further 2 hr before the mixture was concentrated, partitioned between water (10 cm 3 ) and EtOAc (40 cm 3 ) and the aqueous phase washed with CH 2 Cl 2 (3 x 30 cm 3 ) and the combined organic phases dried over sodium sulphate. Purification by flash chromatography (70% toluene in petrol) to give oxazoline 101j (75 mg, 38%). 101k R f : 0.12 (4:1, petrol:EtOAc); MS m/z (ES-) 314 (100%, [M-H] - ), 315 (20%, [(M+1)-H] - ); HRMS: found 338.1143, MNa requires 338.1138; ¹H-NMR (CDCl 3 , 500 MHz) δ 7.63-7.60 (m, 2H, H2, H6), 7.42-7.25 (m, 11H, Ar), 7.00-6.97 (m, 1H, H4), 5.42 (d, 1H, J 7.5, CHOPh), 5.23 (d, 1H, J 7.5, CHNPh); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 164.6 (C=N), 156.3 (C-OH), 141.6 (ipso-Ph), 140.1 (ipso-Ph), 129.8, 128.9, 128.9, 128.5, 128.2, 127.9, 126.7, 125.6 (Ar), 120.6 (C2 or C6), 119.4 (C4), 115.5 (C2 or C6), 89 (CHOPh), 78.4 (CHNPh). 228
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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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Page 185 and 186: References (37) Rawson, D. J.; Meye
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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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