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

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Experimental for chapter 3.2 10.0, H5), 5.17 (dd, 1H, J 10.0, 2.0, H6), 4.39-4.33 (m, 1H, H4), 2.10-1.99 (m, 2H, H3), 1.63-1.58 (m, 2H, H2,CHMe 2 ), 1.20 (s, 3H, Me), 0.96 (d, 3H, J 7.0, CHMe A Me b ), 0.78 (d, 3H, J 7.0, CHMe a Me B ); ¹³C-NMR (CDCl 3 , 125 MHz) δ 202.7 (CHO), 135.5 (C5), 130.7 (C6), 68.5 (C4), 52.3 (C1), 49.2 (C2), 29.5 (C3), 25.8 (CHMe 2 ), 23.5 (CHMe A Me b ), 20.5 (Me), 18.3 (CHMe a Me B ). Synthesis of (1S,4S,5S)-4-(hydroxymethyl)-5-isopropyl-4-methylcyclohex-2-enol (225) Ph O N Ph i) MeOTf, then NaBH 4 ii) H 3 O + iii) NaBH 4 , MeOH HO OH O General procedure 6 was used employing oxazoline 201 (66 mg, 0.18 mmol) and methyl triflate (40 µl, 0.35 mmol) for 18 hr. The crude oxazolidine was subjected to general procedure 7, the room temperature hydrolysis taking 3 days. The resulting crude alcohol was purified by flash column chromatography (2:1 to 1:1 petrol:EtOAc) to give diol 225 (31 mg, 94%) as a colourless oil. R f : 0.12 (1:1, petrol:EtOAc); [α] 22 D : +49.5 (c = 1.1, CHCl 3 ); MS m/z (CI+) 185 (100%, MH + ), 202 (44%, MNH + 4 ), 137 (62%); HRMS: found 202.1808, MNH 4 requires 202.1802; IR ν max (film)/cm⎯¹ 3330 (br, O-H), 2955 (C-H), 2869 (m, C-H), 1462, 1042 (m); ¹H-NMR (CDCl 3 , 500 MHz) δ 5.84-5.81 (m, 1H, H5), 5.41 (dd, 1H, J 10.0, 2.0, H6), 4.26-4.21 (m, 1H, H4), 3.65 (d, 1H, J 11.0, H7 a ), 3.36 (d, 1H, J 11.0, H7 b ), 2.12 (br s, 1H, OH), 1.99 (p, 1H, J 7.0, CHMe 2 ), 1.89-1.83 (m, 1H, H3 a ), 1.77 (br s, 1H, OH), 1.61-1.52 (m, 1H, H3 b ), 1.33 (d, 1H, J 12.5, H2), 0.96 (d, 3H, J 7.0, i- Pr), 0.94 (s, 3H, Me), 0.90 (d, 3H, J 7.0, i-Pr); ¹³C-NMR (CDCl 3 , 125 MHz) δ 136.0 (C5), 133.2 (C6), 69.0 (C4), 67.4 (C7), 47.0, 40.9 (C2, C1), 29.9, 25.3 (C3, CHMe 2 ), 24.5, 24.3, 18.0 (Me). 245
Experimental for chapter 3.2 Synthesis of ((1S,4S,5S)-4-(hydroxymethyl)-5-isopropyl-4-methylcyclohex-2-enol) bis para-bromobenzoate (115) O HO Cl Br Br DMAP Et OH 3 N, CH 2 Cl 2 8 9 O O 7 1 2 3 6 4 5 O O Br 4-bromobenzoyl chloride (120 mg, 0.55 mmol) was added to a solution of diol 225 (20 mg, 0.1 mmol), DMAP (2 mg, 0.02 mmol), triethylamine (1 cm 3 ) in CH 2 Cl 2 (5 cm 3 ) under a nitrogen atmosphere. After 12 hr sodium hydroxide (2.5 cm 3 , 3M aq.) was added to the reaction and stirred for 1 hr before being partitioned in EtOAc (1 cm 3 ) and the organic layer washed sequentially with HCl (3M aq.), sodium bicarbonate, and brine. The organic layer was dried over anhydrous sodium sulphate and solvent evaporated to give a clear yellow oil, which was purified by flash column chromatography (99:1 petrol:EtOAc) to give benzoyl ester 115 (34 mg, 62%) as a white oil. R f : 0.46 (9:1, petrol:EtOAc); [α] 21 D : –15 (c = 1.0, CHCl 3 ); IR ν max (film)/cm⎯¹ 2960 (m), 1717 (C=O), 1590 (m), 1266, 1101 (m); ¹H-NMR (CDCl 3 , 500 MHz) δ 7.92 (d, 2H, J 8.5, H8 or H8'), 7.82 (d, 2H, J 8.5, H8 or H8'), 7.61-7.55 (m, 4H, H9, H9'), 5.78- 5.72 (m, 1H, H5), 5.66 (dd, 1H, J 10.0, 2.0, H6), 5.64-5.59 (m, 1H, H4), 4.34 (d, 1H, J 11.0, H7 a ), 4.26 (d, 1H, J 11.0, H7 b ), 2.19-2.07 (m, 2H, H3, CHMe2), 1.85-1.76 (m, 1H, H3), 1.58 (d, 1H, J 14.0, H2), 1.16 (s, 3H, Me), 1.04 (d, 3H, J 7.0, i-Pr), 0.90 (d, 3H, J 7.0, i-Pr); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 165.6 (C=O), 165.5 (C=O), 137.7 (C6 or C5), 131.8, 131.7, 131.1, 129.3, 129.1, 128.1, 128.1 (Ar), 127.4 (C6 or C5), 72.2 (C4), 68.6 (C7), 46.9, 39.5 (C2, C1), 25.7, 25.5 (C3, CHMe 2 ), 24.5 (CHMe a Me b ), 24.4 (Me), 18.0 (CHMe a Me b ); Chiral HPLC: DAICEL Chiralcel OD-H, 2.5% IPA in hexane, 0.5 ml/min, 11.3 min (0.2%), 12.7 min (99.8%); racemic sample: 11.3 min (49.6%), 12.9 min (50.4%). 246
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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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4.5 - Mannose synthesis hydrolysis
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4.5 - Mannose synthesis The second
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4.6 - Summary 4.6 Summary & Future
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4.6 - Summary OH CDI, NH 2 OH.HCl,
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184
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References (37) Rawson, D. J.; Meye
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References (105) Gajewski, J. J.; B
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References (169) McCormick, J. P.;
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References 192
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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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