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

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Experimental for chapter 4.1 Synthesis of (1S,2R,3S,4R,5R,6S)-1,2-bis(benzyloxy)-5-((4R,5R)-4,5- diphenyloxazolin-2-yl)-3,4-epoxy-6-isopropyl-5-methylcyclohexane (292) Ph Ph Ph Ph Ph Ph O O OH N OH BnBr, DMF, NaH n-Bu 4 NI O O N O N 1 6 2 3 5 4 OBn O 1 6 2 3 5 4 OBn OBn 292 291 OH Adapted from the method of Provelenghi, 19 sodium hydride (7 mg, 0.16 mmol) was added slowly to a solution of benzyl bromide (40 µl, 0.29 mmol), diol 213 (30 mg, 0.07 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 (sat. 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 3:1 petrol:EtOAc) yielded alcohol 291 (24 mg, 68%) and dibenzyl ether 292 (4 mg, 10%) as colourless oils. 292 R f : 0.23 (4:1, petrol:EtOAc); [α] 23 D : +85 (c = 2, CHCl 3 ); MS m/z (ES+) 588 (100%, MH + ), 610 (37%, (M+1)H + ), 610 (80%, MNa + ); HRMS: found 588.3106, MH requires 588.3108; IR ν max (film)/cm⎯¹ 2924 (C-H), 1995 (m), 1640, 1454, 1078; ¹H- NMR (CDCl 3 , 500 MHz) δ 7.41-7.24 (m, 20H, Ph), 5.29 (d, 1H, J 8.5, CHNPh), 5.14 (d, 1H, J 8.5, CHOPh), 5.05 (d, 1H, J 11.5, OBn), 4.81 (d, 1H, J 11.5, OBn'), 4.76 (d, 1H, J 11.5, OBn'), 4.59 (d, 1H, J 11.5, OBn), 4.07 (dd, 1H, J 9.0, 7.0, H3), 3.99 (d, 1H, J 7.0, H4), 3.45 (d, 1H, J 4.0, H6), 3.36 (d, 1H, J 4.0, H5), 1.98 (p, 1H, J 7.0, CHMe 2 ), 1.63-1.57 (m, 4H, H2, Me), 1.11 (d, 3H, J 7.0, i-Pr), 1.03 (d, 3H, J 7.0, i-Pr); ¹³C- NMR (CDCl 3 , 75.5 MHz) δ 169.5, 141.8, 139.5, 139.3, 138.1, 128.7, 128.7, 128.5, 128.4, 128.2, 128.0, 127.7, 127.6, 127.2, 127.1, 126.9, 126.8, 89.7, 83.8, 77.8, 73.2, 72.1, 60.5, 54.0, 53.3, 43.1, 29.7, 26.8, 25.5, 19.8. 255
Experimental for chapter 4.1 291 R f : 0.11 (4:1, petrol:EtOAc); [α] 27 D : +89 (c = 1.2, CHCl 3 ); MS m/z (ES+) 520 (100%, MNa + ), 521 (34%, (M+1)Na + ), 498 (75%, MH + ); HRMS: found 498.2632, MH requires 498.2639; IR ν max (film)/cm⎯¹ 3333 (br, O-H), 2954 (C-H), 1638, 1453, 1076; ¹H-NMR (CDCl 3 , 500 MHz) δ 7.35-7.15 (m, 15H, Ph), 5.19 (d, 1H, J 9.0, CHOPh), 5.05 (d, 1H, J 9.0, CHNPh), 4.78 (d, 1H, J 11.5, OBn), 4.63 (d, 1H, J 11.5, OBn), 4.15-4.09 (m, 1H, H3), 3.63 (dd, 1H, J 8.0, 1.0, H4), 3.38 (dd, 1H, J 4.0, 1.0, H5), 3.21 (d, 1H, J 4.0, H6), 2.28 (s, 1H), 2.17 (d, 1H, J 2.0, C3OH), 1.90 (pd, 1H, J 7.0, 1.0, CHMe 2 ), 1.50 (s, 3H), 1.36 (dd, 1H, J 11.0, 1, H2), 1.01 (d, 3H, J 7.0, i-Pr), 0.94 (d, 3H, J 7.0, i-Pr); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 169.3 (C=N), 141.7 (ipso- Ph), 139.2 (ipso-Ph), 138.0 (ipso-Ph), 129.0, 128.7, 128.7, 128.6, 128.5, 128.2, 127.9, 127.6, 126.9 (Ph), 89.8 (CHOPh), 83.0, 77.5, 71.9, 69.1, 60.4, 53.4, 53.0, 42.7, 29.2, 26.9, 25.7, 18.7. Synthesis of (1S,2S,3R,4S,5R,6R)-5,6-bis(benzyloxy)-3-((4R,5R)-4,5- diphenyloxazolin-2-yl)-4-isopropyl-3-methylcyclohexane-1,2-diol (300) Ph Ph Ph Ph O N O N OsO 4 , NMO, CH 2 Cl 2 HO 6 1 2 OBn OBn HO 5 3 4 OBn OBn General procedure 5 was employed using olefin 289 (26 mg, 0.04 mmol), OsO 4 (0.2 mg, 2 mol %), NMO (12 mg, 0.1 mmol), in CH 2 Cl 2 (0.5 cm 3 ). Upon complete reaction of starting material (c. 9 d), sodium metabisulfite (0.1 cm 3 , 5% w/w aq. solution) was added. Purification by flash chromatography (10% EtOAc in petrol) yielded diol 300 (26 mg, 96 %) as a colourless oil. R f : 0.09 (4:1, petrol:EtOAc); [α] 26 D : +35 (c = 1.2, CHCl 3 ); MS m/z (ES+) 606.4 (100%, MH + ), 607.4 (48%, (M+1)H + ), 628.4 (46%, MNa + ); HRMS: found 606.3222, MH requires 606.3214; IR ν max (film)/cm⎯¹ 3441 (br, OH), 2948 (m, C-H), 1642 (C=N), 1453, 1069; ¹H-NMR (CDCl 3 , 500 MHz) δ 7.37-7.18 (m, 16H, Ph), 7.16-7.08 (m, 4H, Ph), 5.09-5.06 (m, CHOPh, OBn), 4.99 (d, J 9.0, CHNPh), 4.82 (d, J 11.5, OBn'), 4.66 ("t", 2H, J 11.5, OBn, OBn'), 4.29 (dd, 1H, J 10.0, 3.0, H5), 4.09 (dd, 1H, J 11.0, 9.0, H3), 4.00 (d, 1H, J 3, H6), 3.88-3.82 (m, 1H, H4), 2.62 (br s, 1H, OH), 256
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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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Page 285 and 286: Absolute structure parameter 1.3(11
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Page 295 and 296: . Compound 102c Ph O N Ph Me 102c O
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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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