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

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Experimental for chapter 3.1 R f : 0.45 (1:1 petrol:EtOAc); Mpt: 193-194 °C (acetone); [α] 24 D : –2.5 (c = 1.1, DMSO); MS m/z (CI+): 348 (100%, MH + ), 349 (22%, (M+1)H + ), 330 (16%, [M- H 2 O]H + ); HRMS (ESI+) m/z found 348.1591 (MH calcd. 348.1594); IR ν max /cm -1 : 3321 (sharp, OH), 1633 (C=O), 1537, 1244; 1 H-NMR (DMSO, 500 MHz) δ 8.63 (d, 1H, J 9.0, NH), 7.46 (d, 4H, J 7.5, Ph), 7.36-7.27 (m, 5H, Ar), 7.27-7.18 (m, 3H, Ar), 7.15-7.11 (m, 1H, H2), 7.04 (dd, 1H, J 8.0, 2.0, H4), 5.47 (d, 1H, J 5.0, OH), 5.12 (t, 1H, J 9.0, CHNH), 4.92 (dd, 1H, J 8.5, 5.0, CHOH); 13 C-NMR (DMSO, 125 MHz) δ 165.4 (CO), 159.3 (C3), 144.1 (ipso-Ph), 141.9 (ipso-Ph), 136.5, 128.7, 127.3, 127.9, 119.6, 117.0, 112.9, 112.7 (Ar), 74.9 (COH), 55.6 (CNH), 55.4 (OMe). Synthesis of N-((1R*,2S*)-2-hydroxy-1,2-diphenylethyl)-4-phenylbenzamide (165f) Ph O OH Ph i) DMF, (COCl) 2 ii) Ph Ph OH NH 2 (±) Et 3 N Ph HO O NH Ph One drop of DMF was added to a stirred solution of para-biphenyl carboxylic acid (397 mg, 2.0 mmol) and oxalyl chloride (0.19 cm 3 , 2.2 mmol) in CH 2 Cl 2 (4 cm 3 ). Once effervescence had stopped, the solution was allowed to stir for 2 hr, the solvent was removed under reduced pressure, and the crude acid chloride reacted on. General procedure 1 was used mixing the acid chloride with the amino alcohol 174 (511 mg, 2.40 mmol) and triethylamine (0.56 cm 3 , 4.0 mmol) to give amide 165f (650 mg, 83%) as a colourless powder. 1 2 3 4 R f : 0.27 (1:1 petrol:EtOAc); Mpt: 222-224 °C (acetone); MS m/z (CI+): 394 (100%, MH + ), 395 (30%, (M+1)H + ), 376 (100%, [(M-H 2 O)H] + ); HRMS (ESI+) m/z found 394.1803 (MH calcd. 394.1802); IR ν max (film)/cm -1 : 3320 (m), 1635 (C=O), 1540 (m); 1 H-NMR (DMSO, 300 MHz) δ 8.69 (d, 1H, J 9.0, NH), 7.79-7.65 (m, 6H, Ar), 7.52- 7.35 (m, 7H, Ar), 7.34-7.15 (m, 6H, Ar), 5.47 (d, 1H, J 5.0, OH), 5.16 (t, 1H, J 9.0, CHNH), 4.94 (dd, 1H, J 8.5, 5.0, CHOH); 13 C-NMR (DMSO, 75 MHz) δ 164.7 (C=O), 143.6 (C1), 142.5 (ipso-Ph), 141.4 (ipso-Ph), 139.1 (ipso-Ph), 133.3 (ipso-Ph), 219
Experimental for chapter 3.1 128.9, 128.3, 127.9 (para-Ph), 127.7, 127.6, 127.5, 127.0 (para-Ph), 126.8, 126.7, 126.6 (para-Ph), 126.3, 74.5 (CHO), 58.9 (CHN). Synthesis of 4-cyano-N-((1R*,2S*)-2-hydroxy-1,2-diphenylethyl)benzamide (165g) Ph O OH Ph i) DMF, (COCl) 2 HO ii) O NH Ph 1 Ph NH 2 2 CN OH 3 (±) 4 CN (±) One drop of DMF was added to a stirred solution of para-cyanobenzoic acid (500 mg, 3.4 mmol) and oxalyl chloride (0.33 cm 3 , 3.74 mmol) in CH 2 Cl 2 (5 cm 3 ). Once effervescence had stopped the solution was allowed to stir for 1 hr and the solvent was removed under reduced pressure. The crude acyl chloride in CH 2 Cl 2 (5 cm 3 ) was added drop wise over a period of 1 hr to a stirred solution of amine 174 (586 mg, 2.75 mmol) in CH 2 Cl 2 (20 cm 3 ) and Et 3 N (0.69 cm 3 , 5 mmol) at 0 °C. After warming to room temperature, the solution was diluted in CH 2 Cl 2 (10 cm 3 ) and washed with saturated aqueous sodium bicarbonate (20 cm 3 ), the aqueous extract washed with further CH 2 Cl 2 (2 x 20 cm 3 ) and the combined organic extracts dried over sodium sulphate and concentrated under vacuum. The resulting orange oil was purified by flash chromatography (4:1 to 2:1 petrol:EtOAc) to yield amide 165g (480 mg, 41%) as colourless cubes. R f : 0.39 (1:1 petrol:EtOAc); Mpt: 199-200 °C (EtOAc); MS m/z (CI+): 343 (90%, MH + ), 344 (26%, (M+1)H + ), 325 (100%, [M - H 2 O]H + ); HRMS (ESI+) m/z found 343.1434 (MH calcd. 343.1441); IR ν max (film)/cm -1 : 3324 (br, OH), 2232 (m, CH), 1638 (C=O), 1539, 699; 1 H-NMR (CDCl 3 , 500 MHz) δ 7.85 (d, 2H, J 8.0, H2), 7.73 (d, 2H, J 8.0, H3), 7.30-7.22 (m, 6H, Ph), 7.13-7.03 (m, 5H, Ph, NH), 5.45 (dd, 1H, J 8.0, 4.0, CHNH), 5.23 (d, 1H, J 4.0, CHOH); 13 C-NMR (CDCl 3 , 125 MHz) δ 165.2 (C=O), 139.5 (ipso-Ph), 138.2 (ipso-Ph), 136.5 (C1), 132.5 (C2), 128.3, 128.2 (Ph), 128.2 (para-Ph), 128.0 (para-Ph), 127.9, 127.7 (Ph), 126.3 (C3), 117.9 (C4), 115.2 (CN), 76.7 (COH), 59.6 (CNH). 220
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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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Experimental for chapter 4.2 cm 3 )
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Experimental for chapter 4.2 Synthe
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Experimental for chapter 4.2 5.7 Re
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Absolute structure parameter 1.3(11
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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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