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

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Experimental for chapter 3.1 (d, 1H, J 7.5, CHO), 5.25 (d, 1H, J 7.5, CHN), 3.88 (s, 3H, OMe); 13 C-NMR (CDCl 3 , 75 MHz) δ 163.9 (C=N), 159.5 (C3), 141.8 (ipso-Ph), 140.3 (ipso-Ph), 129.4, 128.9, 128.8 (Ar), 128.6 (C1), 128.4, 127.7, 126.7, 125.6 (Ar), 121.0 (C4), 118.5 (C6), 112.7 (C2), 88.9 (CHO), 78.9 (CHN), 55.4 (OMe). Synthesis of (4R*,5R*)-2-(3-fluorophenyl)-4,5-diphenyloxazoline (101d) Ph Ph O NH 2 Ph F i) (Et 3 O)BF 4 ii) Ph NH 2 OH (±) 6 5 O 4 N 1 2 3 F (±) General procedure 3 was used mixing meta-fluorobenzamide (266 mg, 1.91 mmol) with the triethyloxonium salt (400 mg, 2.10 mmol) stirring for 14 hr, before addition of the α-amino alcohol (490 mg, 2.30 mmol) and reflux for 24 hr. Purification by flash chromatography (9:1 petrol:EtOAc), yielded oxazoline 101d (510 mg, 82%) as clear needles. R f : 0.29 (9:1 petrol:EtOAc); Mpt: 63-64 °C (PhMe); MS m/z (CI+): 318 (100%, MH + ), 319 (19%, (M+1)H + ), 211 (63%, [M-PhCHO]H + ); HRMS (ESI+) m/z found 318.1290 (MH calcd. 318.1289); IR ν max (film)/cm -1 : 3031 (w), 1651 (C=N), 1588, 1490 (m), 1453, 1321 (m), 1271 (m), 1185; 1 H-NMR (CDCl 3 , 500 MHz) δ 7.93 (d, 1H, J 8.0, H2), 7.83 (dd, 1H, J 9.5, 1.5, H4), 7.49-7.28 (m, 11H, Ar), 7.27-7.22 (m, 1H, Ar), 5.44 (d, 1H, J 7.5, CHO), 5.25 (d, 1H, J 7.5, CHN); 13 C-NMR (CDCl 3 , 125 MHz) δ 163.0 (C=N), 162.6 (d, J 245, C-F), 141.6 (ipso-Ph), 140.1 (ipso-Ph), 130.2 (d, J 8, C1 or C5), 129.6 (d, J 8, C1 or C5), 129.1, 128.9, 128.0, 127.8, 126.8, 125.9, 125.6, 124.6, 124.1, 118.9, 115.8 (d, J 24, C2 or C4), 115.3 (d, J 24, C2 or C4), 89.2 (CHO), 78.9 (CHN). 225
Experimental for chapter 3.1 Synthesis of (4R*,5R*)-2-(4-cyanophenyl)-4,5-diphenyloxazoline (101g) HO O Ph NH Ph DIC, Cu(OTf) 2 Δ Ph O Ph N 1 2 CN (±) 4 CN 3 (±) General procedure 2 was used with benzamide (340 mg, 1.0 mmol), DIC (0.16 cm 3 , 1.0 mmol), Cu(OTf) 2 (21 mg, 0.06 mmol), THF (3 cm 3 ) and heated under microwave irradiation for 20 min. at 150 °C. Flash chromatography (9:1 petrol:EtOAc) yielded oxazoline 101g (170 mg, 53%) as colourless needles. R f : 0.30 (4:1 petrol:EtOAc); Mpt: 134 °C (PhMe); MS m/z (CI+): 325 (100%, MH + ), 326 (38%, (M+1)H + ), 130 (14%); IR ν max /cm -1 : 2934 (m), 2229 (w, CN), 1628 (C=N), 1527, 1317 (m); 1 H-NMR (CDCl 3 , 400 MHz) δ 8.23 (d, 2H, J 7.0, H2), 7.76 (d, 2H, J 7.0, H3), 7.44-7.25 (m, 10H, Ph), 5.46 (d, 1H, J 8.0, OCH), 5.27 (d, 1H, J 8.0, NCH); 13 C-NMR (CDCl 3 , 100 MHz) δ 162.5 (C=N), 141.3 (ipso-Ph), 139.8 (ipso-Ph), 132.3 (C3) 131.6 (C1), 129.2 (C2), 129.1, 129.0 (Ph), 128.8 (para-Ph), 128.1 (para-Ph), 126.7, 125.8 (Ph), 118.3 (C4), 115.1 (C≡N), 89.6 (HCO), 79.1 (HCN). Synthesis of (4R*,5R*)-2-(4-nitrophenyl)-4,5-diphenyloxazoline (101h) Ph Ph O NH 2 i) (Et 3 O)BF 4 O N ii) Ph 1 2 Ph NH NO 2 2 3 OH (±) 4 NO 2 (±) General procedure 3 was used mixing para-nitrobenzamide (300 mg, 1.81 mmol) with the triethyloxonium salt (378 mg, 2.00 mmol) stirring for 19 hr, before addition of the amino alcohol (462 mg, 2.17 mmol) and reflux for 21 hr. Purification by flash chromatography (19:1 to 9:1 petrol:EtOAc), yielded oxazoline 101h (340 mg, 55%) as colourless flowers. 226
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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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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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