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

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Experimental for chapter 3.1 5.3 Experimental Procedures for Chapter 3.1 Synthesis of (S,S)-hydrobenzoin (176) OH Ph AD mix α, Me 2 SO 2 NH 2 HO Ph Ph t-BuOH/H 2 O Ph By the Method of Sharpless 8 AD mix-α (45.93 g) and methylsulfonamide (4.70 g, 42.3 mmol) were dissolved in t-BuOH (255 cm 3 ) and water (255 cm 3 ) with vigorous stirring and cooled to 0 °C. trans-Stilbene (6.00 g, 33.3 mmol) was added to the solution and stirred for 48 hr. Sodium sulfite (50 g) was added with stirring and allowed to warm to ambient temperature before being partitioned in a separating funnel. The organic phase was concentrated under vacuum and recombined with the aqueous phase, washed with CH 2 Cl 2 (3 x 150 cm 3 ), brine (3 x 200 cm 3 ), and the combined organic phases dried over Na 2 SO 4 , and solvent concentrated under vacuum. The residue was purified by flash chromatography (2:1 EtOAc:petrol) to give hydrobenzoin 176 (7.01 g, 98%) as colourless needles. R f : 0.36 (1:2 petrol:EtOAc); Mpt: 146-147 ºC (petrol/EtOAc), lit. 9 148-150 ºC; [α] 23 D : –94 (c = 1.0, EtOH), lit. 9 –94.1 (c = 1, EtOH); MS m/z (CI + ): 232 (MNH + 4 , 100%), 215 (MH + , 32%); IR ν max /cm -1 : 3498 (br, O–H), 2921, 2896, 1451, 1199, 1045; Microanalysis: % found (% calc’d for C 14 H 14 O 2 ) C, 78.73 (78.48); H, 6.73 (6.59); 1 H- NMR (DMSO, 300 MHz) δ 7.21-7.15 (m, 6H, Ph); 7.11-7.08 (m, 4H, Ph); 5.38* (s, 2H, OH); 4.59 (s, 2H, CH); 13 C-NMR (DMSO, 75 MHz) δ 143.1 (ipso-Ph); 128.0, 127.9, 127.4 (Ph); 78.4 (CH). Synthesis of (4S,5S)-4,5-diphenyl-1,3-dioxolan-2-one (177) O OH HO CDI O O Ph Ph Ph Ph To a stirred solution of (S,S)-hydrobenzoin (3.27 g, 15.2 mmol) in CH 2 Cl 2 (25 cm 3 ) was added CDI (3.71 g, 22.9 mmol). Aqueous hydrochloric acid (50 cm 3 , 1N) was added after 6 hr and the mixture washed with CH 2 Cl 2 (2 x 50 cm 3 ), EtOAc (50 cm 3 ), 211
Experimental for chapter 3.1 saturated aqueous NaHCO 3 (2 x 40 cm 3 ) dried over Na 2 SO 4 and concentrated under vacuum to give cyclic carbonate 177 (3.65 g, 100%) as clear colourless prisms. 20 R f : 0.41 (9:1 petrol:EtOAc); Mpt: 106-108 ºC (CH 2 Cl 2 ); [α] D : –122 (c = 0.5, CH 2 Cl 2 ); MS m/z (CI+): 258 (100%, MNH + 4 ) 259 (18%, (M+1)NH + ), 241 (13%, MH + ); Microanalysis: % found (% calc’d for C 15 H 12 O 3 ) C, 75.22 (74.99); H, 5.06 (5.03); IR ν max /cm -1 : 1822 (C=O), 1458, 1187, 1044; 1 H-NMR (CDCl 3 , 500 MHz) δ 7.46-7.42 (m, 6H, ortho/para-Ph), 7.34-7.30 (m, 4H, meta-Ph), 5.43 (s, 2H, PhCH); 13 C-NMR (CDCl 3 , 125 MHz) δ 154.1 (C=O), 134.8 (ipso-Ph), 129.8, 129.3, 126.1, 85.4 (PhCH). Synthesis of (1S,2R)-2-azido-1,2-diphenylethanol (178) & (2R,3R)-2,3- diphenylaziridine (173) Ph O O O Ph H N i) NaN 3 HO N 3 ii) PPh 3 Ph Ph Ph Ph 178 173 Adapted from the methods of Sharpless 10 sodium azide (894 mg, 13.7 mmol) was added to a stirred solution of cyclic carbonate (3.0 g, 12.5 mmol) in DMF (12 cm 3 ) and water (0.20 cm 3 , 11 mmol) and heated to 110 °C for 48 hr under a nitrogen atmosphere. Upon cooling, the resulting slurry was triturated with Et 2 O (3 x 50 cm 3 ), filtered through Celite, and solvent removed under vacuum distillation to give crude azide 178 as an orange oil. 11 By the method of Blum, 12 crude azide 178 was dissolved in Et 2 O (175 cm 3 ), triphenylphosphine (3.28 g, 12.5 mmol) added and the solution brought to reflux for 2 hr. Et 2 O was added until precipitation stopped, the mixture filtered and the filtrate concentrated under vacuum. Flash chromatography (90:9:1 petrol:EtOAc:Et 3 N) gave aziridine 173 (1.57 g, 64%) as clear needles. R f : 0.16 (9:1 petrol:EtOAc); Mpt: 44-46 ºC (EtOAc), lit. 13 45-46 ºC; [α] D 20 : +350 (c = 0.4, EtOH), lit +328.8 (c = 1.25, CHCl 3 ) 14 ; MS m/z (CI+): 196 (100%, MH + ), (19%, (M+1)H + ); HRMS (ESI+) m/z found 194.0959 (MH calcd. 194.0964); IR 212
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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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Experimental for chapter 4.1 307 R
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Experimental for chapter 4.2 (1S*,2
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Experimental for chapter 4.2 310 R
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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 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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