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

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Experimental for chapter 4.2 (d, 3H, J 7.0, i-Pr); ¹³C-NMR (CDCl 3 , 125 MHz) δ 177.6, 64.9, 60.1, 51.1, 44.6, 43.3, 24.9, 21.4, 17.5, 14.0 Synthesis of (1S,2R,3S,4R,5R,6S)-5-(N-methyl-N-oxo-(4R,5R)-4,5- diphenyloxazolidin-2-yl)-3,4-epoxy-6-isopropyl-5-methylcyclohexane-1,2-diol (332) Ph Ph Ph Ph O N mCPBA, CH 2 Cl 2 O OH OH O O N 1 6 2 3 5 4 mCPBA (37 mg, 50%, 0.11 mmol) was added in a single portion to a stirred solution of allyl alcohol 310 (22 mg, 0.05 mmol) at –40 °C in CH 2 Cl 2 (0.5 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 sulfite (1 cm 3 sat.) was added, the reaction mixture was washed with aqueous sodium bicarbonate (1 cm 3 sat.) and the aqueous phase extracted with further CH 2 Cl 2 (3 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 (9:1 petrol:EtOAc to 10% MeOH in EtOAc) to give epoxide 332 (12 mg, 53%) as a white wax. OH OH R f : 0.28 (9:1, EtOAc:MeOH); [α] 24 D : +125 (c = 1, CHCl 3 ); MS m/z (ES+) 440 (58%, MH + ), 462 (100%, MNa + ); 901 (36%, M 2 Na + ); HRMS: found 440.2428, MH requires 440.2431; IR ν max (film)/cm⎯¹ 3435 (br, OH), 1187, 1121, 1040 (C-O-C), 1010 (m, N- O); ¹H-NMR (CD 3 OD, 500 MHz) δ 7.66-7.62 (m, 2H, Ph), 7.44-7.35 (m, 3H, Ph), 7.34-7.28 (m, 2H, Ph), 7.23-7.19 (m, 3H, Ph), 6.04 (d, 1H, J 11.0, CHOPh), 5.50 (s, 1H, CHNO), 4.67 (d, 1H, J 11.0, CHNPh), 4.07 (dd, 1H, J 11.5, 7.5, H3), 3.86 (d, 1H, J 3.5, H6), 3.61 (dd, 1H, J 7.5, 1.5, H4), 3.23-3.19 (m, 4H, NMe, H5), 2.10 (p, 1H, J 7.0, CHMe 2 ), 1.57 (s, 3H, Me), 1.33 (d, 3H, J 7.0, i-Pr), 1.29 (d, 1H, J 11.5, H2), 1.21 (d, 3H, J 7.0, i-Pr); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 136.6, 132.8, 130.1, 128.4, 128.3, 128.0, 127.1, 126.4 (Ph), 108.1 (CHNO), 87.8 (CHOPh), 81.5 (CHNPh), 77.3 (C4), 71.2 (C3), 61.4 (C6), 57.6 (C2), 54.8 (C5), 42.9 (NMe), 42.8 (C1), 27.5 (i-Pr), 27.2 (CHMe 2 ), 22.7 (Me), 17.4 (i-Pr). 271
Experimental for chapter 4.2 Synthesis of (1R,2S,3R,4S,5S,6S)-5-(hydroxymethyl)-6-isopropyl-5- methylcyclohexane-1,2,3,4-tetraol (324) HO HCl (aq), THF O OH 0 °C - rt OH HO HO HO 1 6 5 4 Aqueous hydrochloric acid (0.3 cm 3 , 6M) was added to a solution of epoxide 309 in THF (0.3 cm 3 ) an ice bath at 0 °C which was allowed to warm to ambient temperature. Solvent was removed from the reaction after 8 hr, and the resulting oil was purified by flash chromatography (2:1 to 2:3 petrol:EtOAc) to yield pentaol 324 (13 mg 81%) as colourless needles. OH 2 3 OH R f : 0.30 (EtOAc); Mpt: 204-5 ºC (MeOH); [α] 23 D : –10.4 (c = 0.5, CHCl 3 ); MS m/z (ES+) 275 (100%, [M+H 2 O]Na + ); HRMS: found 275.1445, [M+H 2 O]Na + requires 275.1465; IR ν max (film)/cm⎯¹ 3325 (br, O-H), 3161 (br, O-H), 2967 (m, C-H), 2913 (m, C-H), 1471 (w, C-Me), 1100, 1058; ¹H-NMR (CD 3 OD, 500 MHz) δ 4.36 (d, 1H, J 3.0, H6), 4.13 (t, 1H, J 3.0, H5), 4.08 (d, 1H, J 11.0, H7 a ), 3.90-3.86 (m, 2H, H3 or H4), 3.48 (d, 1H, J 11.0, H7 b ), 1.94 (p, 1H, J 7.0, CHMe 2 ), 1.69-1.63 (m, 1H, H2), 1.16-1.12 (m, 6H, Me, i-Pr), 1.10 (d, 3H, J 7.0, i-Pr); ¹³C-NMR (CD 3 OD, 75.5 MHz) δ 75.5 (CHOH), 73.7 (CHOH), 70.8 (CHOH), 69.1 (CHOH), 67.1 (C7), 50.4 (C2), 46.2 (C1), 27.6, 27.0, 25.7, 18.6 (Me). 272
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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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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 293 and 294: C24 C23 C22 120.0(2) . . ? C24 C23
Page 295 and 296: . Compound 102c Ph O N Ph Me 102c O
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Page 299 and 300: H11 H 0.8924 0.9592 0.6829 0.022 Ui
Page 301 and 302: C2 H2 1.0000 . ? C3 C21 1.506(2) .
Page 303 and 304: C26 C21 C3 121.41(15) . . ? C23 C22
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Page 311 and 312: H25 H 0.7979 0.2335 0.3365 0.028 Ui
Page 313 and 314: C4 0.025(4) 0.019(4) 0.018(4) 0.001
Page 315 and 316: loop_ _geom_bond_atom_site_label_1
Page 317 and 318: C9 C4 C1 107.1(5) . . ? C10 C4 C1 1
Page 319 and 320: 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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