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

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Experimental for chapter 2 Synthesis of (4R,5R)-2-((1S,6R)-6-isopropyl-4-methoxy-1-methylcyclohexa-2,4- dienyl)-4,5-diphenyloxazoline (102b) Ph Ph O N i) i-PrLi (1.5 eq), DMPU (6 eq) ii) MeI OMe Ph Ph Ph Ph O N O N 1 6 2 5 3 4 + 1 6 2 5 3 4 OMe OMe 102b 103b General procedure 4 was used employing oxazoline 101b (2.00 g, 6.08 mmol) i-PrLi (18.2 mmol in pentane), DMPU (4.41 cm 3 , 36.4 mmol) and methyl iodide (0.76 cm 3 , 12.1 mmol) quench after 10 min. Flash chromatography (19:1 to 4:1 petrol:EtOAc) yielded starting material (110 mg, 6%), oxazoline 103b (370 mg, 18%) as a clear oil and, after recrystallisation from diethyl ether, diene 102b (1.64 g, 70%) as colourless clear cubes. 102b R f : 0.60 (4:1 petrol:EtOAc); Mpt: 113-117 °C (toluene/hexane), 108-110 °C (Et 2 O); [α] 24 D : –115 (c = 0.5, MeOH); MS m/z (CI+): 388 (100%, MH + ), 389 (29%, (M+1)H + ); HRMS (ESI+) m/z found 388.2270 (MH calcd. 388.2271); Microanalysis: % found (% calc’d for C 26 H 29 NO 2 ) C 80.42, (80.59); H, 7.76 (7.54); N, 3.56 (3.61); IR ν max (film)/cm -1 : 2957 (CH), 1661 (C=N), 1453, 1220, 1087; 1 H-NMR (CDCl 3 , 300 MHz) δ 7.46-7.18 (m, 10H, Ph), 6.43 (d, 1H, J 10.0, H5), 5.74 (dd, 1H, J 10.0, 2.0, H6), 5.22 (d, 1H, J 5.0, HCO), 5.06 (d, 1H, J 5.0, HCN), 4.53 (dd, 1H, J 6.5, 2.0, H3), 3.62 (s, 3H, OMe), 2.59 (ddd, 1H, J 6.5, 3.5, 1.0, H2), 2.08-1.96 (m, 1H, CHMe 2 ), 1.57 (s, 3H, Me), 1.00 (d, 3H, J 6.5, CHMe a Me b ), 0.96 (d, 3H, J 6.5, CHMe a Me b ); 13 C- NMR (CDCl 3 , 125 MHz) δ 171.2 (C=N), 153.1 (C4), 141.9, 140.3 (ipso-Ph), 135.0 (C5), 128.9 (meta-Ph), 128.7 (meta-Ph), 128.3 (para-Ph), 127.6 (para-Ph), 126.7 (ortho-Ph), 125.7 (ortho-Ph), 121.6 (C6), 89.0 (COPh), 88.4 (C3), 78.8 (HCN), 54.2 (OMe), 46.8 (C2), 41.9 (C1), 31.7 (CMe 2 ), 25.8 (CMe), 21.2 (CMe a Me b ), 17.0 (CMe a Me b ). 103b R f : 0.50 (4:1 petrol:EtOAc); [α] D 22 : –44 (c = 1.0, EtOH); MS m/z (CI+): 344 (100%, MH + ), 345 (22%, (M+1)H + ); HRMS (ESI+) m/z found 344.1645 (MH calcd. 344.1645); IR ν max (film)/cm -1 : 2927 (m, C-H), 1637 (C=N), 1605, 1247; 1 H-NMR 199
Experimental for chapter 2 (CDCl 3 , 300 MHz) δ 8.00 (d, 1H, J 8.5, H6), 7.46-7.28 (m, 10H, Ph), 6.86-6.78 (m, 2H, H3, H5), 5.31 (d, 1H, J 7.5, CHO), 5.26 (d, 1H, J 7.5, CHN), 3.86 (s, 3H, OMe), 2.73 (s, 3H, CMe); 13 C-NMR (CDCl 3 , 125 MHz) δ 164.7 (C=N), 161.3 (C4), 142.5 (C2), 141.7 (ipso-Ph), 140.9 (ipso-Ph), 132.0, 128.9, 128.8, 128.3, 127.6, 126.6, 125.7, 119.2, 116.8, 110.9 (Ar), 87.8 (COPh), 79.3 (CNPh), 55.3 (OMe), 22.7 (Me). Synthesis of (4R,5R)-2-((1S,6R)-6-sec-butyl-4-methoxy-1-methylcyclohexa-2,4- dienyl)-4,5-diphenyloxazoline (102b’) Ph Ph Ph Ph Ph Ph O N i) s-BuLi (3 eq), DMPU (6 eq) -78 °C, 10 min ii) MeI O 1 6 5 N 7 2 3 4 8 9 10 11 + O N OMe OMe dr 7:2 OMe 102b' 103b' General procedure 2 was used employing oxazoline 101b (100 mg, 0.30 mmol) s-BuLi (0.90 mmol in hexanes), DMPU (0.22 cm 3 , 36.4 mmol) and methyl iodide (0.1 cm 3 ) quench after 10 min. Flash chromatography (49:1 to 4:1 petrol:EtOAc) yielded starting material (5 mg, 5%) and oxazolines 102b’ and 103b’ (94 mg, 78%, 9:1 mixture) as a clear oil. R f : 0.29 (9:1, petrol:EtOAc); [α] 22 D : –104 (c = 1.0, CHCl 3 ); MS m/z (CI+) 402 (100%, MH + ), 403 (27%, [(M+1)H] + ); HRMS: found 402.2431, MH requires 402.2428; IR ν max (film)/cm⎯¹ 2959 (m), 1661 (C=N), 1452 (m), 1215, 1173 (m), 1086; ¹H-NMR (major compound) (CDCl 3 , 500 MHz) δ 7.42-7.28 (m, 8H, Ph), 7.24-7.20 (m, 2H, Ph), 6.43 (d, 1H, J 10.0, H6), 5.74 (dd, 1H, J 10.0, 2.0, H5), 5.22 (d, 1H, J 8.5, CHOPh), 5.05 (d, 1H, J 8.5, CHNPh), 4.47 (dd, 1H, J 6.5, 2.0, H3), 3.61 (s, 3H, OMe), 2.73- 2.68 (m, 1H, H2), 1.71-1.64 (m, 1H, H9), 1.57 (s, 3H, H7), 1.42-1.32 (m, 1H, H10), 1.28-1.20 (m, 1H, H10’), 0.99 (d, 3H, J 6.5, H8), 0.95-0.90 (m, 3H, H11); ¹³C-NMR (CDCl 3 , 125 MHz) δ 171.2 (C=N), 153.0 (C4), 141.9 (ipso-Ph), 140.4 (ipso-Ph), 135.1 (C5), 128.7, 128.7, 127.6, 126.7, 125.7 (Ph), 121.7 (C6), 89.0, 88.6 (CHOPh, C3), 78.9 (CHNPh), 54.2 (OMe), 44.8 (C2), 41.7 (C1), 39.0 (C9), 27.6 (C10), 25.8 (C7), 14.8, 12.4 (C8, C11). 200
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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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Page 177 and 178: 4.5 - Mannose synthesis The second
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Page 181 and 182: 4.6 - Summary OH CDI, NH 2 OH.HCl,
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Page 185 and 186: References (37) Rawson, D. J.; Meye
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Page 193 and 194: Experimental section 254nm, dodecam
Page 195 and 196: Experimental section General Proced
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Experimental for chapter 4.1 combin
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Experimental for chapter 4.1 Synthe
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Experimental for chapter 4.1 291 R
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Experimental for chapter 4.1 3H, OB
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Experimental for chapter 4.2 (1S*,2
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Experimental for chapter 4.2 10.0,
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Experimental for chapter 4.2 cm 3 )
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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
show all

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