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

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Experimental for chapter 4.1 2.30 (br s, 1H, OH), 2.10 (pd, 1H, J 7.0, 1.0, CHMe 2 ), 1.99 (dd, 1H, J 11.0, 1.0, H2), 1.53 (s, 3H, Me), 1.11 (d, 3H, J 7.0, CHMe A Me b ), 1.01 (d, 3H, J 7.0, CHMe a Me B ); ¹³C- NMR (CDCl 3 , 75.5 MHz) δ 169.4 (C=N), 141.4 (ipso-Ph), 139.5 (ipso-Ph), 139.2 (ipso-Ph), 138.5 (ipso-Ph), 129 (para-Ph), 128.9 (Ph), 128.8 (Ph), 128.7 (Ph), 128.5 (para-Ph), 128.2 (Ph), 128.2 (para-Ph), 127.9 (Ph), 127.7 (para-Ph), 127.1, 127, 126.6, 126.1 (Ph), 88.8 (CHOPh), 85.9 (CHOR), 80.1 (CHOR), 78.2 (CHNPh), 75.6 (OBn), 75.1 (CHOR), 72.8 (OBn), 71.9 (CHOR), 49.1 (C2), 45.7 (C1), 27.6 (CHMe 2 ), 26.7 (Me), 22.4 (CHMe A Me b ), 19.5 (CHMe a Me B ). Synthesis of (1R,2S,3S,4S,5R,6S)-2,3,4,5-tetra(benzyloxy)-1-((4R,5R)-4,5- diphenyloxazolin-2-yl)-6-isopropyl-1-methylcyclohexane (302) HO HO Ph O N OBn Ph OBn BnBr, DMF, NaH n-Bu 4 NI BnO BnO Ph 5 O 6 1 N Ph 2 OBn 3 4 OBn BnO HO Ph 5 O 6 1 N Ph 2 3 4 OBn OBn Adapted from the method of Provelenghi, 19 sodium hydride (5 mg, 0.12 mmol) was added slowly to a solution of benzyl bromide (20 µl, 0.15 mmol), diol 300 (23 mg, 0.04 mmol) and tetrabutylammonium iodide (1 mg, 0.003 mmol) in DMF (0.8 cm 3 ) whilst the reaction mixture was maintained at ambient temperature. When the reaction was judged complete (c. 16 hr) aqueous ammonium chloride (saturated, 0.1 cm 3 ) was added to the reaction, the solvent removed under vacuum and the resulting residue partitioned between water (2 cm 3 ) and CH 2 Cl 2 (6 cm 3 ). The aqueous phase was washed with further CH 2 Cl 2 (2 x 5 cm 3 ) and the combined organic phases dried over sodium sulphate, before purification by flash chromatography (19:1 to 9:1 petrol:EtOAc) yielded alcohol 301 (14 mg, 54%), perbenzyl ether 302 (10 mg, 33%) and starting material (2 mg, 9%) as colourless oils. 302 R f : 0.45 (9:1, petrol:EtOAc); [α] 24 D : +21 (c = 1, CHCl 3 ); MS m/z (ES+) 786 (67%, MH + ), 808 (100%, MNa + ), 809 (52%, (M+1)Na + ); HRMS: found 786.4159, MH requires 786.4153; IR ν max (film)/cm⎯¹ 2930 (m, C-H), 1453 (m, C-Me), 1069; ¹H- NMR (CDCl 3 , 500 MHz) δ 7.36-7.10 (m, 30H, Ph), 5.20 (d, 1H, J 11.5, CHOPh), 5.12 (s, 2H, OBn), 5.09 (d, 1H, J 11.5, CHNPh), 5.01 (d, 1H, J 10.5, OBn), 4.79-4.71 (m, 257
Experimental for chapter 4.1 3H, OBn), 4.69 (d, 1H, J 11.0, OBn), 4.65 (d, 1H, J 11.5, OBn), 4.22 (dd, 1H, J 10.0, 8.5, H4), 4.18-4.10 (m, 2H, H5, H3), 4.02 (d, 1H, J 2.0, H6), 2.07 (pd, 1H, J 7.0, 1.5, CHMe 2 ), 2.01 (dd, 1H, J 11.0, 1.5, H2), 1.57 (s, 3H, Me), 1.13 (d, 3H, J 7.0, CHMe A Me b ), 1.08 (d, 3H, J 7.0, CHMe a Me B ); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 169.7 (C=N), 141.7 (ipso-Ph), 139.7 (ipso-Ph), 139.6 (ipso-Ph), 138.9 (ipso-Ph), 138.8 (ipso- Ph), 138.7 (ipso-Ph), 128.9, 128.7, 128.7, 128.3, 128.3, 128.2, 128.1, 127.8, 127.7, 127.4, 127.4, 127.1, 126.9, 126.5, 126.3 (Ph), 88.6 (CHOPh), 85.5, 82.3, 81.8, 80.7 (C3, C4, C5, C6), 77.9 (CHNPh), 75.9 (OCH 2 Ph), 75.4 (OCH 2 Ph), 72.8 (OCH 2 Ph), 72.7 (OCH 2 Ph), 49.1, 47.0 (C1, C2), 28.2 (CHMe 2 ), 27.3 (CHMe A Me b ), 23.2 (Me), 19.4 (CHMe a Me B ). 301 R f : 0.24 (4:1, petrol:EtOAc); [α] 27 D : +24 (c = 1, CHCl 3 ); MS m/z (ES+) 696 (100%, MH + ), 697 (36%, (M+1)H + ), 718 (29%, MNa + ); HRMS: found 696.3681, MH requires 696.3686; IR ν max (film)/cm⎯¹ 3582 (O-H), 2924 (C-H), 1641 (C=N), 1453 (C- Me), 1069; ¹H-NMR (CDCl 3 , 500 MHz) δ 7.46-7.16 (m, 23H, Ph), 7.14-6.99 (m, 2H, Ph), 5.15 (d, 1H, J 9.0, CHOPh), 5.13 (d, 1H, J 11.5, OBn), 5.08 (d, 1H, J 9.0, CHNPh), 4.90 (d, 1H, J 11.0, OBn), 4.86 (d, 1H, J 11.0, OBn), 4.76 (dd, 2H, J 11.0, 2.0, OBn), 4.73-4.67 (m, 2H, OBn), 4.25 (ddd, 1H, J 10.0, 5.5, 3.0, H5), 4.19 (dd, 1H, J 11.0, 8.5, H3), 4.00 (dd, 1H, J 10.0, 8.5, H4), 3.94 (d, 1H, J 3.0, H6), 2.11 (pd, 1H, J 7.0, 1.5, CHMe 2 ), 2.02 (d, 1H, J 5.5, C5-OH), 2.01 (dd, J 11.0, 1.5, H2), 1.62 (s, 3H, Me), 1.16 (d, 3H, J 7.0, CHMe A Me b ), 1.11 (d, 3H, J 7.0, CHMe a Me B ); ¹³C-NMR (CDCl 3 , 125 MHz) δ 169.6 (C=N), 141.6 (ipso-Ph), 139.6 (ipso-Ph), 138.7 (ipso-Ph), 138.5 (ipso-Ph), 128.9, 128.8, 128.6, 128.4, 128.2, 128.1, 127.9, 127.7, 127.1, 127.0, 126.5, 126.2 (Ph), 88.8 (CHOPh), 86.4 (C4), 84.8 (C3), 80.5 (C6), 78.3 (CHNPh), 76.5 (OCH 2 Ph), 75.1 (OCH 2 Ph), 72.8 (OCH 2 Ph), 72.7 (C5), 49.5 (C2), 47.3 (C1), 28.0, 28.0 (CHMe 2 , CHMe A Me b ), 27.2 (Me), 19.7 (CHMe a Me B ). 258
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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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Page 285 and 286: Absolute structure parameter 1.3(11
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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
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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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