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

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Experimental for chapter 4.1 Synthesis of (1R,2S,3S,4S,5S,6S)-tetrakis(benzyloxy)5-((benzyloxy)methyl)-6- isopropyl-5-methylcyclohexane (304) BnO BnO Ph O N OBn Ph OBn i) MeOTf, then NaBH 4 ii) H 3 O + 60 °C iii) NaBH 4 BnO BnO HO 6 5 1 7 2 3 4 OBn OBn General procedure 6 was used employing oxazoline 302 (20 mg, 0.025 mmol) and methyl triflate (6 µl, 0.05 mmol) for 20 hr. The crude oxazolidine was subjected to general procedure 7, hydrolysis at 60 °C taking 7 days. The resulting crude alcohol was purified by flash column chromatography (4:1 petrol:EtOAc) to give alcohol 304 (9 mg, 60%) as a colourless oil. R f : 0.30 (40%, EtOAc in petrol); [α] 24 D : +135 (c = 1, CHCl 3 ); MS m/z (ES+) 430 (100%, MNa + ), 408 (27%, MH + ), 838 (39%, 2MNa + ); HRMS: found 430.2349, MNa requires 430.2353; IR ν max (film)/cm⎯¹ 3364 (br, OH), 2947 (m), 2360 (w, C=C), 1453 (m); ¹H-NMR (CDCl 3 , 500 MHz) δ 7.31-7.25 (m, 3H, Ar), 7.23-7.16 (m, 5H, Ar), 7.05-7.00 (m, 2H, Ar), 6.06 (dd, 1H, J 10.0, 2.0, H5), 5.65 (dd, 1H, J 10.0, 2.0, H6), 4.74 (d, 1H, J 9.0, CHOPh), 4.54 (s, 1H, CHON), 4.24 (dd, 1H, J 11.5, 7.0, H3), 3.95 (br d, 1H, J 7.0, H4), 3.30 (d, 1H, J 9.0, CHNPh), 2.37 (s, 3H, NMe), 2.31-2.10 (m, 3H, CHMe 2 & OH), 1.48 (d, 1H, J 11.5, H2), 1.29 (d, 3H, J 7.0, CHMe A Meb), 1.21- 1.17 (m, 6H, Me & CHMeaMe B ); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 138.6 (ipso-Ph), 137.6 (ipso-Ph), 134.7 (C5), 128.3 (C6), 128.1, 128.0, 127.8, 127.7, 126.4 (Ph), 99.9 (CHON), 85.6 (CHOPh), 79.6 (CHNPh), 76.1 (C4), 74.1 (C3), 55.1 (C2), 48.6 (C1), 41.9 (NMe), 27.3 (CHMeaMe B ), 25.9 (CHMe 2 ), 24.7 (Me), 17.9 (CHMe A Meb). 259
Experimental for chapter 4.1 Synthesis of (1R,2S,3S,4S,5S,6S)-5-(hydroxymethyl)-6-isopropyl-5- methylcyclohexane-1,2,3,4-tetraol (278) BnO BnO HO OBn OBn Pd(OH) 2 , MeOH H 2 , 20 bar Benzyl ether 304 (3 mg, 5 µmol) was dissolved in MeOH (0.5 cm 3 ) and passed through a Pd(OH) 2 H-Cube cartridge at 20 bar H 2 , flow rate 0.5 cm 3 min -1 . The solvent was removed from the resulting solution to yield pentaol 278 (1 mg, quant.) as colourless needles. HO HO OH OH OsO 4 , quinuclidine, MeSO 2 NH 2 , K 2 CO 3 , K 3 Fe(CN) 6 , t-BuOH/H 2 O HO HO HO HO 5 HO 6 1 OH 7 2 3 OH 4 OH OH Adapted from the method of Warren 20 osmium tetroxide (20 µl of 2.5% solution in t- BuOH) was added to a vigorously stirred orange solution of triol 312 (16 mg, 0.08 mmol) in t-BuOH (0.4 cm 3 ), H 2 O (0.4 cm 3 ) with potassium ferricyanide (79 mg, ground, 0.24 mmol), potassium carbonate (33mg, 0.24 mmol), methyl sulfonamide (8 mg, 0.08 mmol) and quinuclidine (1 mg, 0.01 mmol). When complete my TLC analysis (c. 72 hr) excess sodium sulfite was added, and the decolourised reaction mixture partitioned between EtOAc (5 cm 3 ) and water (2 cm 3 ), the aqueous layer was washed with EtOAc (5 x 5 cm 3 ), the combined organic extracts dried over anhydrous sodium sulfate and solvent removed to yield a white solid (16 mg). Flash column chromatography (EtOAc to 1% MeOH in EtOAc) yields pentaol 278 (15 mg, 79%) as colourless needles. R f : 0.09 (EtOAc); Mpt: 175 ºC (MeOH); [α] 22 D : +7.2 (c = 1.0, MeOH); MS m/z (ES–) 269 (100%, MCl 35- ), 271 (34%, MCl 37- ), 233 (32%, M – ), 467 (16%, 2M – ); HRMS: found 269.1179, MCl requires 269.1161; IR ν max (film)/cm⎯¹ 3364 (br, OH), 2943 (m), 1021 (w); ¹H-NMR (D 2 O, 500 MHz) δ 3.81 (d, 1H, J 3.0, H6), 3.66 (dd, 1H, J 10.0, 3.0, H5), 3.62-3.56 (m, 1H), 3.56-3.49 (m, 3H), 1.93 (p, 1H, J 7.0, CHMe 2 ), 1.48 (d, 1H, J 11.5, H2), 1.06 (s, 3H, Me), 1.03 (d, 3H, J 7.0, i-Pr), 0.93 (d, 3H, J 7.0, i-Pr); 260
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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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Page 285 and 286: Absolute structure parameter 1.3(11
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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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