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

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Chapter 1: Introduction Again a large range of nucleophiles and electrophiles were tolerated. Temperature was found to have a significant effect on the diastereoselectivity of addition by vinyllithium (Table 1.6, entries f, g). Studies of protic quenches found that the use of trifluoroacetic acid (TFA) gave the expected trans-dihydronaphthalene 41 rather than its epimer as had previously been observed (Scheme 1.11). It is proposed that this is due to trifluoroacetate being too weak a base to epimerise the allylic stereocentre. Quenching with TFA led to the formation of TFA salt 41 upon workup, which could be reduced to give carbinol 42 and is discussed further in section 3.2.1. Ph O N OMe i) i-PrLi ii) TFA O H Ph O i-Pr NH 2 OMe i) LiAlH 4 , Et 2 O ii) H 2 O, NaOH H OH i-Pr 38 41 42 73% d.r. 24:1 Scheme 1.11 – TFA quench of dearomatising addition It has also been possible to perform a tandem addition to naphthalene 38 by tethering an electrophilic site to the organolithium, giving an effective stereoselective annulation to yield syn-fused carbocycle 43 in good yield. Ph O N OMe i) Li Cl THF −78 °C to rt Ph O OMe N ii) NH 4 Cl H 38 43 84% Scheme 1.12 – annulation by ambident organolithium 33 29
1.3 – Nucleophilic dearomatisation The effect of oxazoline substituents on diastereoselectivity was investigated using 2- naphthyloxazolines 44 (Table 1.7). This work shows that the C4 substituent was key to determining the stereochemistry of the product (entries a, b, d) whilst the C5 substituent shows minimal effect except when syn to the C4 substituent (entry c). Similar results were seen for 1-naphthyloxazolines in the same study. Oxz i) PhLi ii) MeI Ph Oxz + Ph Oxz 44 45a 45b Entry T / °C Oxz Yield / % 45a : b Ph 5 4 a –30 O N OMe 89 90 : 10 Me b –78 O N OMe 90 9 : 91 Me c –78 O N OMe 93 25 : 75 d –78 O N OMe 90 9 : 91 Table 1.7 – the effect of oxazoline substituents on diastereoselectivity 31 To explain the high diastereoselectivity, Meyers proposes a bidentate interaction between the aryloxazoline and organolithium (Scheme 1.13); the two remaining coordination sites around lithium being occupied by solvent and the alkyl group, and are free to interchange. 34 30
Page 1 and 2: Dearomatising Addition of Organolit
Page 3 and 4: 2.3 Synthetic Scope 64 2.3.1 Organo
Page 5 and 6: Abstract Dearomatising Addition of
Page 7 and 8: The Author The Author graduated fro
Page 9 and 10: Abbreviations & Conventions Ac acet
Page 11 and 12: RDS rate determining step R f RC rt
Page 14 and 15: Chapter 1: Introduction Chapter 1 -
Page 16 and 17: Chapter 1: Introduction controlled
Page 18 and 19: Chapter 1: Introduction diastereome
Page 20 and 21: Chapter 1: Introduction combine mor
Page 22 and 23: Chapter 1: Introduction O Ar Cl TMP
Page 24 and 25: Chapter 1: Introduction conditions,
Page 26 and 27: Chapter 1: Introduction chiral oxaz
Page 30 and 31: Chapter 1: Introduction 34 Scheme 1
Page 32 and 33: Chapter 1: Introduction The amino a
Page 34 and 35: Chapter 1: Introduction It was envi
Page 36 and 37: Chapter 1: Introduction COR' i) ATP
Page 38 and 39: Chapter 1: Introduction O i) ATPH,
Page 40 and 41: Chapter 1: Introduction 1.4 Nucleop
Page 42 and 43: Chapter 1: Introduction Unlike the
Page 44 and 45: Chapter 1: Introduction Diene (-)-8
Page 46 and 47: Chapter 1: Introduction A scheme su
Page 48 and 49: Chapter 1: Introduction Cl R + 93 S
Page 50 and 51: Chapter 2 - Dearomatising additions
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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 3.1 128.9,
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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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