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

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Experimental for chapter 4.2 Synthesis of (1R,2R,5S,6S)-5-(hydroxymethyl)-6-isopropyl-5-methylcyclohex-3- ene-1,2-diol (312) Ph Ph O NMe i) H 3 O + , 50 °C HO 6 1 2 OH OH ii) NaBH 4 5 4 OH 3 OH General procedure 7 was employed using oxazolidine 310 (50 mg, 0.12 mmol), and the reaction heated at 50 °C for 24 hr. Flash chromatography (3:2 petrol:EtOAc) yielded triol 312 (19 mg, 79%) as colourless needles. R f : 0.34 (EtOAc); Mpt: 136-138 ºC (MeOH); [α] 22 D : +10.8 (c = 1.7, MeOH); MS m/z (ES+) 223 (100%, MNa + ), 224 (15%, (M+1)Na + ); HRMS: found 223.1299, MNa requires 223.1305; IR ν max (film)/cm⎯¹ 3348 (br, O-H), 2958 (m, C-H), 1651 (w, C=C); ¹H-NMR (CD 3 OD, 500 MHz) δ 5.60 (dd, 1H, J 10.0, 1.5, H5), 5.44 (dd, 1H, J 10.0, 2.0, H6), 4.00 (d, 1H, J 7.5, H4), 3.91 (dd, 1H, J 12.0, 7.5, H3), 3.59 (d, 1H, J 11.0, H7), 3.39 (d, 1H, J 11.0, H7’), 2.03 (p, 1H, J 7.0, CHMe 2 ), 1.48 (d, 1H, J 12.0, H2), 1.19 (d, 6H, J 7.0, i-Pr), 1.01 (s, 3H, Me); ¹³C-NMR (CD 3 OD, 75.5 MHz) δ 136.8 (C5), 129.3 (C6), 76.3 (C4), 74.1 (C3), 67.7 (C7), 53.7 (C2), 44.9 (C1), 27.5 (CHMe 2 ), 27.5 (CHMe A Me B ), 24.7 (Me), 18.1 (CHMe A Me B ). For dihydroxylation of 312 to give altrose analogue 278, see page 260 Synthesis of (1S,4R,5R,6S)-5-hydroxy-6-isopropyl-1-methylcyclohex-2-ene-δlactone (328) Ph Ph O N Me MeOTf, then NH 4 Cl O 1 2 OH O 4 3 OH OH General procedure 6 was used employing oxazoline 213 (45 mg, 0.11 mmol) and methyl triflate (27 µl, 0.23 mmol) for 16 hr and an ammonium chloride (sat. aq., 0.5 269
Experimental for chapter 4.2 cm 3 ) quench. The layers were partitioned, the aqueous layer washed with CH 2 Cl 2 (2 x 5 cm 3 ) and the combined organic phases dried over anhydrous sodium sulfate. Flash chromatography (9:1 to 1:1 petrol:EtOAc) gave lactone 328 (8 mg, 36%) as a colourless oil. R f : 0.09 (4:1, petrol:EtOAc); [α] 24 D : +187 (c = 0.8, CHCl 3 ); MS m/z (ES-) 391 (100%, [2M-H] – ), 195 (40%, [M-H] – ), 196 (4%, [(M+1)-H] – ); IR ν max (film)/cm⎯¹ 3432 (br, OH), 2964 (m, C-H), 1758 (C=O); ¹H-NMR (CDCl 3 , 500 MHz) δ 5.93 (d, 1H, J 9.0, H6), 5.79-5.74 (dm, 1H, J 9.0, H5), 4.54-4.50 (m, 1H, H4), 4.37-4.32 (m, 1H, H3), 2.16 (d, 1H, J 3.5, H2), 2.01 (pd, 1H, J 7.0, 3.5, CHMe 2 ), 1.91 (br d, 1H, J 6.0, H3), 1.32 (s, 3H, Me), 1.04 (d, 3H, J 7.0, i-Pr), 0.87 (d, 3H, J 7.0, i-Pr); ¹³C-NMR (CDCl 3 , 125 MHz) δ 179.0 (C=O), 139.2, 128.2, 66.8, 50.8, 25.5, 21.5, 17.6, 14.9. (1S,2S,3R,4R,5R,6S)-2,3-epoxy-5-hydroxy-6-isopropyl-1-methylcyclohexane-δlactone (329) O O Me OH mCPBA O Me 1 2 O O 4 3 OH mCPBA (17 mg, 50%, 0.05 mmol) was added in a single portion to a stirred solution of allyl alcohol 328 (5 mg, 0.05 mmol) at –20 °C in CH 2 Cl 2 (0.3 cm 3 ) and maintained at the temperature for 4 hr, after which period the reaction was allowed to warm to rt. After 18 hr, aqueous sodium bicarbonate (1 cm 3 sat.) was added, the reaction partitioned, and the aqueous phase extracted with further CH 2 Cl 2 (2 x 5 cm 3 ). The combined organic layers were dried over anhydrous sodium sulfate, and the solvent removed. The resulting mixture was purified by flash column chromatography (4:1 petrol:EtOAc) to give epoxide 329 (4 mg, 80%) as a colourless oil. R f : 0.29 (2:1, petrol:EtOAc); [α] 24 D : +78 (c = 0.5, CHCl 3 ); MS m/z (ES–) 211 (100%, (M-H) – ), 212 (9%, ([M+1]-H) – ), 423 (90%, (2M-H) – ); HRMS: found 212.1044, M requires 212.1043; IR ν max (film)/cm⎯¹ 3431 (br, O-H), 2964 (m, C-H), 1779 (C=O), 1261 (m); ¹H-NMR (CDCl 3 , 500 MHz) δ 4.33-4.29 (m, 1H, H3 or H4), 4.10-4.04 (m, 1H, H3 or H4), 3.37-3.32 (m, 2H, H5, H6), 2.32 (d, 1H, J 3.5, H2), 2.19 (br s, 1H, OH), 1.89 (pd, 1H, J 7.0, 3.5, CHMe 2 ), 1.41 (s, 3H, Me), 0.99 (d, 3H, J 7.0, i-Pr), 0.83 270
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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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Experimental for chapter 2 H4), 5.2
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Experimental for chapter 2 108 R f
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Experimental for chapter 2 Synthesi
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Experimental for chapter 3.1 satura
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Experimental for chapter 3.1 Na 2 S
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Experimental for chapter 3.1 Synthe
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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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Page 313 and 314: C4 0.025(4) 0.019(4) 0.018(4) 0.001
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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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