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

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Experimental for chapter 4.2 Synthesis of (1R,2S,3S,4S,5R,6S)-6-isopropyl-5-methyl-5-(N-methyl-(4R,5R)-4,5- diphenyloxazolidin-2-yl)cyclohexane-1,2,3,4-tetraol (311) Ph Ph Ph Ph Ph Ph Ph Ph O N O NMe O NMe O NMe 1 OsO 4 HO 6 HO 2 OH CH 2 Cl 2 , NMO 5 HO 3 4 OH OH HO OH OH OH O O 311 318 319 General procedure 5 was employed using olefin 310 (20 mg, 0.05 mmol), OsO 4 (12 µl, 2.0 mol%), NMO (12 mg, 0.10 mmol), in CH 2 Cl 2 (0.5 cm 3 ). Upon complete reaction of starting material (7 days), sodium metabisulfite (0.2 cm 3 , 5% w/w aq. solution) was added. Purification by flash chroma<strong>to</strong>graphy (19:1 <strong>to</strong> 1:2 petrol:EtOAc) yielded tetraol 311 (4 mg, 21%), enone 318 (2 mg, 11%) and triol 319 (8 mg, 42%) as colourless oils. 311 R f : 0.23 (2:1, petrol:EtOAc); [α] 20 D : +14 (c = 1, CHCl 3 ); MS m/z (ES–) 442 (100%, MH + ), 443 (31%, (M+1)H + ); HRMS: found 442.2584, MH requires 442.2588; IR ν max (film)/cm⎯¹ 3398 (br, O-H), 2927 (m, C-H), 2360 (w), 1457 (w), 1065; ¹H- NMR (CDCl 3 , 500 MHz) δ 7.33-7.27 (m, 6H, Ph), 7.22-7.16 (m, 2H, Ph), 7.08-6.99 (m, 2H, Ph), 4.63 (d, 1H, J 9.0, CHOPh), 4.59 (d, 1H, J 3.0, H6), 4.51 (s, 1H, CHNO), 4.15 (dd, 1H, J 11.0, 9.0, H3), 3.95-3.90 (m, 1H, H5), 3.71 (t, 1H, J 9.0, H4), 3.35 (d, 1H, J 9.0, CHNPh), 2.29 (s, 3H, NMe), 2.13 (p, 1H, J 7.0, CHMe 2 ), 1.74 (d, 1H, J 11.0, H2), 1.29 (d, 3H, J 7.0, CHMe A Me b ), 1.28 (s, Me), 1.20 (d, 3H, J 7.0, CHMe a Me B ); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 139.2 (ipso-Ph), 137.1 (ipso-Ph), 128.544, 128.3, 128.0, 127.7, 126.3 (Ph), 101.2 (CHNO), 85.2 (CHOPh), 79.7 (CHNPh), 76.8 (CHOH), 73.6 (CHOH), 73.5 (CHOH), 72.6 (CHOH), 52.2 (C2), 47.2 (C1), 39.7 (NMe), 27.7 (CHMe a Me B ), 25.3 (CHMe 2 ), 23.144 (Me), 18.2 (CHMe A Me b ). 318 R f : 0.20 (9:1, petrol:EtOAc); [α] 24 D : +268 (c = 1, CHCl3); MS m/z (ES+) 428 (100%, MNa + ), 429 (32%, (M+1)H + ); HRMS: found 428.2191, MNa requires 428.2196; IR ν max (film)/cm⎯¹ 3383 (m, O-H), 2947 (m, C-H), 2355 (m), 1675 (C=O), 1450 (w, C-Me), 1061 (m); ¹H-NMR (CDCl 3 , 500 MHz) δ 7.34-7.29 (m, 4H, Ph, H6), 7.27-7.23 (m, 3H, Ph), 7.18-7.15 (m, 2H, Ph), 7.03-6.99 (m, 2H, Ph), 6.22 (d, 1H, J 267
Experimental for chapter 4.2 10.0, H5), 4.86 (dd, 1H, J 13.0, 1.0, H3), 4.82 (s, 1H, CHON), 4.62 (d, 1H, J 9.5, CHOPh), 3.42 (br d, 1H, J 1.0, OH), 3.38 (d, 1H, J 9.5, CHNPh), 2.45 (s, 3H, NMe), 2.26 (p, 1H, J 7.0, CHMe 2 ), 1.85 (d, 1H, J 13.0, H2); 1.39 (s, 3H, Me), 1.37 (d, 3H, J 7.0, CHMe A Me b ), 1.21 (d, 3H, J 7.0, CHMe a Me B ); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 202.9 (C=O), 157.6 (C6), 137.8 (ipso-Ph), 136.9 (ipso-Ph), 128.5, 128.1, 128.1, 128.0, 128.0, 126.4, 126.3 (Ph), 100.6 (CHNO), 86.6 (CHOPh), 79.6 (CHNPh), 72.2 (C3), 56.6 (C2), 49.4 (C1), 41.7 (NMe), 26.6 (CHMe a Me B ), 26.5 (CHMe 2 ), 24.2 (Me), 17.5 (CHMe A Me b ). 319 R f : 0.33 (0.4, EtOAc in petrol); [α] 22 D : +43 (c = 1.3, CHCl 3 ); MS m/z (ES+) 440 (100%, MH + ), 441 (29%, (M+1)H + ); HRMS: found 440.2434, MH requires 440.2431; IR ν max (film)/cm⎯¹ 3474 (O-H), 2950 (m, C-H), 1717 (C=O), 1453 (m); ¹H-NMR (CDCl 3 , 500 MHz) δ 7.37-7.25 (m, 6H, Ph), 7.23-7.18 (m, 2H, Ph), 7.10-7.04 (m, 2H, Ph), 4.98 (br d, 1H, J 11.0, H3), 4.87 (d, 1H, J 3.0, H5 or H6), 4.80 (d, 1H, J 3.0, H5 or H6), 4.69-4.64 (m, 2H, CHNO, CHOPh), 3.81 (br s, 1H, OH), 3.45 (d, 1H, J 9.0, CHNPh), 3.23. (br d, 1H, J 3.0, C3-OH), 2.65 (br s, 1H, OH), 2.35 (s, 3H, NMe), 2.24 (p, 1H, J 7.0, CHMe 2 ), 2.01 (d, 1H, J 11.5, H2), 1.38 (s, 3H, Me), 1.35 (d, 3H, J 7.0, i- Pr), 1.18 (d, 3H, J 7.0, i-Pr); ¹³C-NMR (CDCl 3 , 125 MHz) δ 138.6, 136.6, 128.7, 128.3, 128.2, 128.1, 126.4, 101.2, 86.2, 79.7, 74.7, 74.2, 57.0, 46.0, 39.4, 27.2, 25.9, 22.8, 18.1. 268
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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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Experimental section 254nm, dodecam
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Experimental section General Proced
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Experimental for chapter 2 Synthesi
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Experimental for chapter 2 (CDCl 3
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Experimental for chapter 2 3H, OMe
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Experimental for chapter 2 Ph), 139
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Experimental for chapter 2 H4), 5.2
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Experimental for chapter 2 108 R f
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Experimental for chapter 2 Synthesi
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Experimental for chapter 3.1 satura
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Experimental for chapter 3.1 Na 2 S
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Page 285 and 286: Absolute structure parameter 1.3(11
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Page 289 and 290: H13 H 0.8405 0.7136 -0.0889 0.026 U
Page 291 and 292: C4 C5 1.454(2) . ? C5 C6 1.324(2) .
Page 293 and 294: C24 C23 C22 120.0(2) . . ? C24 C23
Page 295 and 296: . Compound 102c Ph O N Ph Me 102c O
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Page 299 and 300: H11 H 0.8924 0.9592 0.6829 0.022 Ui
Page 301 and 302: C2 H2 1.0000 . ? C3 C21 1.506(2) .
Page 303 and 304: C26 C21 C3 121.41(15) . . ? C23 C22
Page 305 and 306: c. Compound 213 Ph O N Ph Me OH 213
Page 307 and 308: _cell_volume 1080.9(4) _cell_formul
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Page 311 and 312: H25 H 0.7979 0.2335 0.3365 0.028 Ui
Page 313 and 314: C4 0.025(4) 0.019(4) 0.018(4) 0.001
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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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