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

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Experimental for chapter 3.1 101b data as enantiopure (vide infra) Chiral HPLC: Pircle Covalent (R,R) Whelk-O1 column, 10% IPA in hexane, 1ml/ min: 50% - 11.3 min, 50% - 20.0 min. Synthesis of (4R, 5R)-2-(4-methoxyphenyl)-4,5-diphenyloxazoline (101b) HO O Ph NH Ph DIC, Cu(OTf) 2 Ph O N Ph Δ OMe OMe Reflux:General procedure 2 was used with benzamide (20.0 mg, 57.6 mmol), DIC (8.96 cm 3 , 57.6 mmol), Cu(OTf) 2 (1.25 g, 3.50 mmol), dioxane (175 cm 3 ) and heated under reflux for 12 hr at 120 °C. Flash chromatography (9:1 to 4:1 petrol:EtOAc) yielded oxazoline 101b (8.67 g, 46%) as colourless needles. Microwave:General procedure 2 was used with benzamide (700 mg, 2.01 mmol), DIC (0.31 cm 3 , 2.01 mmol), Cu(OTf) 2 (44 mg, 0.12 mmol), THF (7 cm 3 ) and heated under microwave irradiation for 30 min. at 140 °C. Flash chromatography (9:1 to 4:1 petrol:EtOAc) yielded oxazoline 101b (661 mg, 72%) as colourless needles. Ph Ph Ph Ph Ph O N Ph SiO 2 slurry, CH 2 Cl 2 O 1 N O N 2 OMe 3 4 OMe OMe 101b 109b An excess of silica was added to a stirred solution of aziridine 100b (1.38 g, 4.2 mmol) in CH 2 Cl 2 (20 cm 3 ) and stirred for 8 days. The mixture was filtered, concentrated under vacuum and purified by flash chromatography (9:1 to 3:1 petrol:EtOAc) to yield oxazoline 101b (800 mg, 58%) as clear cubic crystals, and its diastereomeric oxazoline 109b (7 mg, 1%). 223
Experimental for chapter 3.1 R f : 0.38 (4:1 petrol:EtOAc); Mpt: 98-99 °C (toluene); [α] 32 D : –40.8 (c = 1.0, CHCl 3 ); [α] 20 D : –38 (c = 0.5, EtOH); MS m/z (CI+): 330 (100%, MH + ), 331 (21%, (M+1)H + ); HRMS (ESI+) m/z found 330.1488 (MH calcd. 330.1489); Microanalysis: % found (% calc’d for C 22 H 19 NO 2 ) C, 80.22 (80.00), H, 5.81 (5.81), N 4.25 (4.23); IR ν max (film)/cm -1 : 1641 (C=N), 1608, 1510, 1254; 1 H-NMR (CD 3 OD, 300 MHz) δ 8.06 (d, 2H, J 9.0, H2), 7.51-7.29 (m, 10H), 7.09 (d, 2H, J 9.0, H3), 5.49 (d, 1H, J 7.5, CHO), 5.18 (d, 1H, J 7.5, CHN), 3.92 (s, 3H, OMe); 1 H-NMR (CDCl 3 , 300 MHz) δ 8.10 (d, 2H, J 9.0, H2), 7.45-7.31 (m, 10H), 6.99 (d, 2H, J 9.0, H3), 5.40 (d, 1H, J 7.5, CHO), 5.21 (d, 1H, J 7.5, CHN), 3.89 (s, 3H, OMe); 13 C-NMR (CD 3 OD, 125 MHz) δ 165.4 (C=N) 163.3 (C4), 141.8 (ipso-Ph), 140.2 (ipso-Ph), 130.3, 128.9, 128.8, 128.5, 127.9, 126.7, 125.6 (Ph), 119.0 (C1), 114.0 (C3), 89.5 (CHOPh), 78.5 (CHNPh), 54.8 (OMe); chiral HPLC: Pirkle Covalent (R,R) Whelk-O1 column, 10% IPA in hexane, 1ml min -1 , 100%, 11.7 min; racemic sample: 50% - 11.3 min, 50% - 20.0 min. See appendix for crystallographic information. 109b characterised separately (vide infra) Synthesis of (4R,5R)-2-(3-methoxyphenyl)-4,5-diphenyloxazoline (101c) HO Ph Ph Ph Ph O NH DIC, Cu(OTf) 2 O N Δ 6 1 2 OMe 5 4 3 OMe General procedure 2 was used with benzamide 165c (195 mg, 0.56 mmol), DIC (0.09 cm 3 , 0.56 mmol), Cu(OTf) 2 (12 mg, 0.03 mmol), dioxane (2 cm 3 ) and heated under reflux for 17 hr. Flash chromatography (4:1 petrol:EtOAc) yielded oxazoline 101c (71 mg, 39%) as colourless needles. R f : 0.38 (4:1 petrol:EtOAc); Mpt: 92-93 °C (PhMe); [α] 21 D : –25.0 (c = 0.4, EtOH); MS m/z (CI+): 330 (100%, MH + ), 331 (23%, (M+1)H + ), 223 (23%); HRMS (ESI+) m/z found 330.1495 (MH calcd. 330.1489); IR ν max (film)/cm -1 : 1646 (C=N), 1582, 1452, 1321, 1039; 1 H-NMR (CDCl 3 , 300 MHz) δ 7.75 (dt, 1H, J 8.0, 1.0, H6), 7.71- 7.69 (m, 1H, H2), 7.17-7.06 (m, 11H, Ph, H5), 7.11 (ddd, 1H, J 8.0, 2.5, 1.0, H4), 5.43 224
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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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Page 185 and 186: References (37) Rawson, D. J.; Meye
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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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