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

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Chapter 3 – Oxazoline synthesis & removal Ph NH 3 Cl Ph O 211.HCl c-Hex O Pd/C, H 2 1 atm, 1 hr LiBH 4 , THF, 0 °C O c-Hex O OH H N HO c-Hex Ph 205 H 2 N Ph quant Ph 212 Ph 50% Scheme 3.27 – reduction of ester 211 Cyclohexanecarboxylic acid was easily recovered from the hydrogenation, which did not require workup, whilst reduction with ethereal lithium borohydride returned mostly amide 205, rather than the desired alcohol. Disappointingly precipitation could not be induced with arene 101b, and amide 211, the thermodynamic product, was isolated in near quantitative yield (Scheme 3.28). Ph O N Ar 101b Ph HCl (aq), EtOH Δ 12 hr O Ar H N 211 Ph OH Ph 96% Scheme 3.28 – hydrolysis of aryl oxazolines Ar = MeO Hydrolysis of diol 213 and enone 201 both precipitated the ester as the major product, although enone 201 gave equal amounts of the ester and an unidentified oil. The IR spectrum of this oil contained only one strong absorption at 1672 cm -1 , likely to be the enone, and NMR analysis showed no significant aromatic or isopropyl peaks. Whilst attempting the epoxide opening of 216, ester 217 was isolated in good yield, but was not reacted further (Scheme 3.29). 119
3.2 – Oxazoline removal Ph Ph Ph Ph O N O OR O N O OR OH 213 OH HCl (aq), THF Δ, 12 hr OH 214 OH 80% 6N HCl:THF 2:1 Δ, < 18hr O O 201 215 45% R = Ph NH 3 Cl O Ph Ph O N Ph HClO 4 (aq), dioxane O OR O rt, 28 hr O OH OH OH 216 217 OH 40% (55% conv) Scheme 3.29 – hydrolysis of oxazolines to esters Since the amide would be expected to be the thermodynamic product of these reactions, and it was isolated in the absence of a precipitate, it is believed that the precipitate serves to move the hydrolysis equilibrium in favour of the ester. In light of this, other ammonium salts were tried; exposure and gentle heading of cyclohexane 101m with solutions of HBF 4 , HCl/Et 2 O, H 2 SO 4 and TsOH did not promote any visible precipitation. The alkylation-hydrolysis of enone 201 was attempted in a similar fashion to Meyers (section 3.2.1.a). The resulting ester is closely related to the ammonium salt 211, and was isolated in slightly improved yield with some starting material recovered. Ph Ph Ph O N MeOTf, 16 hr then NH 4 Cl (aq) 24 hr, rt MeHN Ph O O O 201 O 218 60% (90% conv.) Scheme 3.30 – alkylation-hydrolysis of oxazoline 201 120
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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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Page 68 and 69: Chapter 2 - Dearomatising additions
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Page 95 and 96: 3.1 - Oxazoline synthesis 3.1.1.a H
Page 97 and 98: 3.1 - Oxazoline synthesis O Ar OH i
Page 99 and 100: 3.1 - Oxazoline synthesis 3.1.2 Gen
Page 101 and 102: 3.1 - Oxazoline synthesis mCPBA O N
Page 103 and 104: 3.1 - Oxazoline synthesis 3.1.4.b M
Page 105 and 106: 3.1 - Oxazoline synthesis Ph Ph Ph
Page 107 and 108: 3.2 - Oxazoline removal O N O OH 3N
Page 109 and 110: 3.2 - Oxazoline removal O Me O N OM
Page 111 and 112: 3.2 - Oxazoline removal However, th
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Page 115 and 116: 3.2 - Oxazoline removal Ph O N Ph P
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Page 121 and 122: 3.2 - Oxazoline removal 3.2.5.b N-A
Page 123 and 124: 3.2 - Oxazoline removal Ph Ph O N H
Page 125 and 126: 3.2 - Oxazoline removal Ph Me Ph Me
Page 127 and 128: 3.2 - Oxazoline removal 3.2.6 Deter
Page 129 and 130: Better, however, would be a method
Page 131 and 132: 4.1 - Introduction HO OH OH HO OH O
Page 133 and 134: 4.1 - Introduction (-)-Shikimic aci
Page 135 and 136: 4.1 - Introduction followed by Flem
Page 137 and 138: 4.2 - Carbasugar synthesis 4.2 Synt
Page 139 and 140: 4.2 - Carbasugar synthesis stereoce
Page 141 and 142: 4.2 - Carbasugar synthesis of the o
Page 143 and 144: 4.2 - Carbasugar synthesis support
Page 145 and 146: 4.2 - Carbasugar synthesis Ox* Ox*
Page 151 and 152: 4.2 - Carbasugar synthesis OsO 4 (c
Page 153 and 154: 4.2 - Carbasugar synthesis taken on
Page 155 and 156: 4.2 - Carbasugar synthesis As well
Page 157 and 158: 4.4 - Revised altrose synthesis 4.4
Page 159 and 160: 4.4 - Revised altrose synthesis suf
Page 161 and 162: 4.4 - Revised altrose synthesis ind
Page 163 and 164: 4.5 - Mannose synthesis 4.5 Synthes
Page 165 and 166: 4.5 - Mannose synthesis It is clear
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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 3.1 128.9,
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Experimental for chapter 3.1 Microw
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Experimental for chapter 3.1 R f :
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Experimental for chapter 4.1 281 R
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Experimental for chapter 4.1 combin
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Experimental for chapter 4.1 3H, OB
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Experimental for chapter 4.2 (1S*,2
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Experimental for chapter 4.2 10.0,
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Experimental for chapter 4.2 cm 3 )
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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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