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

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Experimental for chapter 3.2 324.1958; IR ν max (film)/cm⎯¹ 3315 (br, O-H), 2931 (C-H), 1641 (C=O), 1534 (N-H); ¹H-NMR (CDCl 3 , 500 MHz) δ 7.25-7.23 (m, 10H, Ph), 6.32 (d, 1H, J 7.5, NH), 5.23 (dd, 1H, J 8.0, 4.5, CHNPh), 4.30 (d, 1H, J 4.5, CHOPh), 2.09 (tt, 1H, J 11.5, 3.0, CH), 1.81-1.71 (m, 4H), 1.67-1.61 (m, 1H), 1.36-1.15 (m, 5H); ¹³C-NMR (CDCl 3 , 125 MHz) δ 176.4 (C=N), 140.7 (ipso-Ph), 139.6 (ipso-Ph), 128.7, 128.2 (Ph), 127.7 (para- Ph), 127.7 (para-Ph), 126.8, 126 (Ph), 77.2 (CHOPh), 59 (CHNPh), 45.4 (CH), 29.6, 29.4, 25.6, 25.6 (CH 2 ). Synthesis of (3S*,4S*)-N-((S*)-1,2-diphenylethyl)-3-isopropyl-4-methylcyclohexanone-4-carboxamide (206) Ph O N Ph H 2 Pd/C 20 bar Ph Ph H N O O O A solution of oxazoline 201 (90 mg, 0.24 mmol) in methanol (6 cm 3 ) was passed thorough the H-cube (1 cm 3 /min, 20 bar, Pd/C) and the eluent collected for 30 min. The solvent was removed by rotary evaporation to give amide 206 (93 mg, 96%) as a colourless oil. R f : 0.10 (4:1, petrol:EtOAc); MS m/z (CI+) 378 (100%, MH + ), 379 (24%, (M+1)H + ); HRMS: found 378.2425, MH requires 378.2428; IR ν max (film)/cm⎯¹ 2932 (m, C-H), 1714 (ketone), 1639 (amide), 1531 (m, N-H), 1453 (m); ¹H-NMR (CDCl 3 , 500 MHz) δ 7.37-7.18 (m, 8H, Ph), 7.11-7.16 (m, 2H, Ph), 5.93 (br d, 1H, J 8.0, NH), 5.39-5.29 (m, 1H, CHNPh), 3.23 (dd, 1H, J 14.0, 6.0, CH 2 Ph), 3.02 (dd, 1H, J 14.0, 9.0, CH 2 Ph), 2.96-2.85 (m, 1H), 2.93 (dd, 1H, J 14.5, 12.0), 2.74 (ddd, 1H, J 15.5, 11.5, 6.5), 2.17- 2.11 (m, 2H), 1.82-1.75 (m, 2H, CHMe 2 , CH), 1.59-1.53 (m, 2H), 1.20 (s, 3H, J 6.5, Me), 0.81 (d, 3H, J 6.5, i-Pr), 0.52 (d, 3H, i-Pr); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 213.4, 174.5, 141.5, 137.3, 129.2, 128.6, 128.4, 127.5, 126.7, 126.5, 53.7, 51.8, 43.2, 42.7, 38.3, 38.1, 37.0, 27.7, 24.5, 23.7, 17.2. 237
Experimental for chapter 3.2 Synthesis of (1R*,2R*)-2-(cyclohexylmethylamino)-1,2-diphenylethanol (210) Ph O N Ph DIBALH (3 eq) 0 °C H N Ph OH Ph O H N Ph OH Ph 210 205 A solution of DIBAlH (0.24 cm 3 , 1M in PhMe, 3 eq) was added drop wise to a stirred solution of oxazoline 101m (22 mg, 0.07 mmol) in toluene (1 cm 3 ) under a nitrogen atmosphere, maintained at 0 °C for 4 hr before warming to rt and stirred for 16 hr. Ammonium chloride (sat. aq. 2 cm 3 ) was added and stirred for 2 hr before being partitioned between water (2 cm 3 ) and CH 2 Cl 2 (10 cm 3 ) and the aqueous layer was extracted with CH 2 Cl 2 (3 x 10 cm 3 ) and the combined organic layers dried with sodium sulfate and reduced under vacuum. Flash chromatography (9:1 petrol:EtOAc) yielded amine 210 (17 mg, 80%) as a colourless oil and hydroxyamide 205 (2 mg, 10%). 210 R f : 0.26 (4:1, petrol:EtOAc+Et 3 N); MS m/z (CI+) 310 (100%, MH + ), 311 (19%, (M+1)H + ), 202 (68%, [M-PhCH 2 OH] + ); HRMS: found 310.2176, MH requires 310.2165; IR ν max (film)/cm⎯¹ 3400 (br, N-H, O-H), 2922 (C-H), 1451 (m, C-H); ¹H- NMR (CDCl 3 , 500 MHz) δ 7.24-7.16 (m, 6H, Ph), 7.09-7.07 (m, 2H, Ph), 7.02-6.98 (m, 2H, Ph), 4.55 (d, 1H, J 9.0 CHOPh), 3.53 (d, 1H, J 9.0 CHNPh), 2.77 (br s, 2H, OH, NH), 2.38 (dd, 1H, J 11.5, 6.5, H5), 2.27 (dd, 1H, J 11.5, 6.5 H5’), 1.79-1.62 (m, 5H), 1.46-1.38 (m, 1H), 1.26-1.10 (m, 3H), 0.95-0.82 (m, 2H); ¹³C-NMR (CDCl 3 , 125 MHz) δ 141.2 (ipso-Ph), 140.0 (ipso-Ph), 128.2, 127.8, 127.6, 127.3, 126.8 (Ph), 77.6 (CHOPh), 70.8 (CHNPh), 54.2 (CH 2 N), 38.2 (CH), 31.4, 31.2, 26.6, 26.0, 26.0 (CH 2 ). 205: see page 236 238
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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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Page 185 and 186: References (37) Rawson, D. J.; Meye
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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
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