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

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Experimental for chapter 4.1 Synthesis of (1R,2S,5S,6S)-5-((4R,5R)-4,5-diphenyloxazolin-2-yl)-6-isopropyl-5- methylcyclohex-3-ene-1,2-diol (287) Ph Ph Ph Ph Ph Ph O N O N O N O OH CeCl 3. 7H 2 O, NaBH 4 1 MeOH, 0 °C OH OH 213 287 6 5 2 3 4 OH OH Sodium borohydride (24 mg, 0.63 mmol) was added portion wise to a stirred solution of enone 276 (100 mg, 0.26 mmol) and cerium trichloride heptahydrate (97 mg, 0.26 mmol) in methanol (0.6 cm 3 ) at 0 °C. When judged complete by TLC (PMA stain c. 20 min) ammonium chloride (sat. aqueous) was added to the cooled reaction mixture until. The solvent was removed from the reaction mixture, which was partitioned between water (3 cm 3 ) and CH 2 Cl 2 (10 cm 3 ) and the aqueous layer further washed (2 x 10 cm 3 CH 2 Cl 2 ) and the combined organic layers washed with brine before being dried over sodium sulphate. Removal of solvent gave a mixture of diols 213 and 287 (100 mg, 99%, 10:1 mixture) which were separated by recrystallisation from Et 2 O and forming the acetonide of 287. 213 – see page 250 287 R f : 0.23 (2:1, petrol:EtOAc); [α] 22 D : +216 (c = 0.5, CHCl 3 ); MS m/z (CI+) 410 (100%, MH + ), 411 (23%, (M+1)H + ); HRMS: found 432.2146, MNa requires 432.2145; IR ν max (film)/cm⎯¹ 3359 (br), 2923 (m), 1639, 1451 (m), 1382, 1258; ¹H- NMR (CD 3 OD, 500 MHz) 7.43-7.30 (m, 8H, Ph), 7.27-7.23 (m, 2H, Ph), 5.92 (dd, 1H, J 5.0, 10.0, H5), 5.72 (d, 1H, J 10.0, H6), 5.24 (d, 1H, J 10.5, CHOPh), 5.02 (d, 1H, J 10.5, CHNPh), 4.21 (dd, 1H, J 12.0, 4.5, H3), 4.06 (t, 1H, J 4.5, H4), 2.73 (sept, 1H, J 7.0, CHMe2), 1.84 (d, 1H, J 12.0, H2), 1.48 (s, 3H, Me), 1.19 (d, 3H, J 7.0, CHMe A Me B ), 1.12 (d, 3H, J 7.0, CHMe A Me B ); ¹³C-NMR (CDCl 3 , 125 MHz) δ 169.5 (C=N), 140.9 (ipso-Ph), 138.9 (ipso-Ph), 137.5 (C5), 128.8 (C6), 128.7, 128.5, 127.7, 126.8 , 126.1, 125.7 (Ph), 90.0 (CHOPh), 78.0 (CHNPh), 69.0 (C3), 66.7 (C4), 48.7 (C2), 44.2 (C1), 26.7 (Me), 26.4 (CHMe 2 ), 26.0 (Me), 17.5 (CHMe a Me b ). 251
Experimental for chapter 4.1 Synthesis of (2R,3S,4S)-4-((4R,5R)-4,5-diphenyloxazolinyl)-2-hydroxy-3- isopropyl-4-methylcyclohexanone (288) Ph Ph Ph Ph O N DIBAlH, CH 2 Cl 2 O N −78 °C OH OH O O A solution of DIBAlH (0.18 cm 3 , 1M in CH 2 Cl 2 ) was added drop wise to a stirred solution of oxazoline 276 (60 mg, 0.15 mmol) in CH 2 Cl 2 (2 cm 3 ) at –78 °C under a nitrogen atmosphere to give a clear yellow solution. After 90 min, methanol (0.5 cm 3 ) was added in a single portion to the cooled solution followed by ammonium chloride (sat. aq. 2 cm 3 ) and the reaction warmed to rt. The resulting solution was partitioned between water (2 cm 3 ) and EtOAc (10 cm 3 ) and the aqueous layer was extracted with EtOAc (3 x 10 cm 3 ) and the combined organic layers dried with sodium sulfate and reduced under vacuum. Flash chromatography (petrol to 4:1 petrol:EtOAc) yielded ketone 288 (8 mg, 15%) as a colourless oil and starting material (35 mg, 58%). R f : 0.49 (2:1, petrol:EtOAc); [α] 22 D : –132 (c = 0.8, CHCl 3 ); MS m/z (CI+) 392 (100%, MH + ), 393 (25%, (M+1)H + ), 180 (53%), 305 (13%); HRMS: found 392.2227, MH requires 392.2220; IR ν max (film)/cm⎯¹ 3414 (br, O-H), 2928 (m, C-H), 1710 (C=O), 1644 (C=N), 1451 (m), 1112 (m), 1085 (m), 1058 (m); ¹H-NMR (CDCl 3 , 500 MHz) δ 7.44-7.28 (m, 8H, Ph), 7.24-7.20 (m, 2H, Ph), 5.21 (d, 1H, J 9.5, CHOPh), 5.11 (d, 1H, J 9.5, CHNPh), 4.68 (dd, 1H, J 12.0, 2.0, H3), 3.70 (d, 1H, J 2.0, OH), 3.39 (tdd, 1H, J 14.0, 6.5, 1.0, H5 ax ), 2.52 (ddd, 1H, J 14.0, 4.5, 2.5, H5 eq ), 2.42 (ddd, 1H, J 14.0, 6.5, 2.5, H6 eq ), 2.32 (p, 1H, J 7.0, CHMe 2 ), 1.79 (td, 1H, J 14.0, 4.5, H6 ax ), 1.57 (d, 1H, J 12.0, H2), 1.50 (s, 3H, Me), 1.18-1.12 (m, 6H, CHMe 2 ); ¹³C-NMR (CDCl 3 , 125 MHz) δ 212.8 (C4), 170.0 (C=N), 141.3 (ipso-Ph), 139.5 (ipso-Ph), 129.0 (meta-Ph), 128.9 (meta-Ph), 128.6 (para-Ph), 127.8 (para-Ph), 126.6 (ortho-Ph), 126.0 (ortho-Ph), 88.8 (COPh), 78.2 (CNPh), 74.6 (C3), 59.8 (C2), 41.3 (C1), 39.3 (C5), 36.7 (C6), 28.2 (CHMe 2 ), 26.6, 26.2, 17.9 (Me). 252
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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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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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