My PhD dissertation - Institut Fresnel

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4.1 Preparation of Enantiomerically Pure 6,6’- Dibromobiphenyl-2,2’-diol and Derivatives Thereof Since A. Rajca et al. [ 172] 40 described the preparation of 2,2',6,6'- tetrabromobiphenyl (30) in two step with a very low overall yield (31%), synthesis of biphenyl 30 was first attempted in a one step procedure. The oxidative coupling of 2- hydroxynaphtalene with iron(III) chloride to form 2,2'-dihydroxy-1,1'-binaphtyl (BINOL) inspired this investigation and suggested the use of different metallic oxidants. For this purpose, commercially available 1,3-dibromobenzene was first metalated at -75 °C with lithium diisopropylamine (LIDA) in tetrahydrofuran to selectively afford 1,3-dibromo-2- lithio-benzene [ ] 174 . The transient species produced was then treated with various salts such as iron(III) chloride or chromium(III) chloride at -75 °C, but the yield of biphenyl 30 was unfortunately very low (8 to 14%) or even not existent. As the reaction effectively happened but appeared to be sluggish at low temperature, the transient lithio- species was transmetalated to its organozinc derivative by addition of anhydrous zinc(II) bromide at -75 °C. The latter, more stable towards aryne formation, could hence be warm up to 0 °C and treated with iron(III) chloride to afford 30 in 33% yield. However low, this yield remained unoptimized and offers the promising advantage to produce the halogenated biphenyl in one step. LiC 4H 9, THF Br Br - 75 °C Br Br Li [ ] 173 ZnBr 2, - 75 °C FeCl 3, O °C Br Br Br Br Br Br ZnBr 30, 33% 2,2',6,6'-Tetrabromobiphenyl (30) was, in parallel, efficiently prepared in two steps from 1,3-dibromobenzene, following F. Leroux's modification [53] of the procedure described by A. Rajca et al. [172] . The previously metalated 1,3-dibromobenzene was first treated with iodine to afford 1,3-dibromo-2-iodobenzene (29) in nearly quantitative yield (96%). LIDA, THF I 2, THF Br Br - 75 °C Br Br Br Br Li I 29, 96%
41 Since the homocoupling of the haloarene 29 to give biphenyl 30 by the classical Ullmann reaction gave only poor yields, A. Rajca's procedure [172] was employed after slight optimizations. Thus, iodobenzene derivative 29 was treated with butyllithium in diethyl ether, followed by addition of copper(II) bromide to form presumably the diarylcuprate. Although the dimerization of "lower order" cuprates (e.g. R2CuLi) has already been achieved by oxidation with some copper(II) salts [ , ] 175 176 , the copper species formed in our case apparently followed a different mechanism had to be oxidized with nitrobenzene to afford 30 in 64% yield. Br I 29 Br LiC 4H9, DEE - 75 °C Br Br CuBr 2 - 75 °C Br Cu Br Br PhNO 2 Li Br Br Br Br Br 30, 64% Since the two step preparation route to biphenyl 30 was applicable to a large scale reaction and gave better overall yield, it was finally used to routinely prepare this starting material. The tetrabromobiphenyl 30 thus formed had then to be turned into different chiral and resolvable motifs. Therefore, 6,6’-dibromobiphenyl-2,2’-diol (31), and 6,6’- dibromobiphenyl-2,2’-dicarboxylic acid (37) were prepared, and resolved through inclusion complex or diastereomeric salts formation. The choice of phenol and carboxylic acid functions was motivated by two main aspects. First of all, both functions are prone to form inclusion complex with chiral hosts, or can be deprotonated with any kind of chiral base to form diastereomeric salt, this property being essential for the racemate resolution to be achieved. On the other hand, both phenol and carboxylic acid functions can be easily derivatized, reduced, or even halogenated to allow various modifications on the chiral biphenyl unit. 4.1.1 Racemic 6,6’-Dibromobiphenyl-2,2’-diol Tetrabromobiphenyl 30 was first subjected to a double permutational bromine/lithium exchange in tetrahydrofuran at -75 °C. Treatment of the transient 2,2'- dibromo-6,6'-dilithiobiphenyl with fluorodimethoxyborane-diethyl ether [ , ] 177 178 followed by hydrogen peroxide in alkaline media afforded the expected biphenol 31 in 76% yield after recrystallization. However, since this compound was formed quantitatively and without any
Page 1:
Various Facets of Organophosphorus
Page 5:
III Remerciements Je tiens à remer
Page 9: 3.3.6 Relevance of the Data Assesse
Page 13: VII Literature References 115 Compo
Page 17: IX Version Abrégée Les composés
Page 21 and 22: 1 Introduction 1 The present thesis
Page 23 and 24: 3 research groups in the field are
Page 25 and 26: 5 However, this mechanism suffers f
Page 27: 7 At first, a double bromine/lithiu
Page 30 and 31: 10 Although the most frequently emp
Page 32 and 33: 12 The preparation of the latter ph
Page 34 and 35: protected to its dioxolane derivati
Page 36 and 37: N (S)-14 1) NBS, THF, - 75 °C 2) -
Page 39 and 40: 3 Alkaline Decomposition of Phospho
Page 41 and 42: 3.2 Alkyl Carbanions Stabilities in
Page 43 and 44: 3.3.1 Mechanistic Discussion on the
Page 45 and 46: 25 The assumption reported by these
Page 47 and 48: 27 However, in the eventuality of a
Page 49 and 50: 29 To prepare tertiary phosphines b
Page 51 and 52: 31 Table 4. Mixed tertiary alkylpho
Page 53 and 54: 33 were comparable to those obtaine
Page 55 and 56: 35 led to the formation of di-tert-
Page 57 and 58: 37 depending on the alkyl substitue
Page 59: 39 4 A Novel Access to Atropisomeri
Page 63 and 64: 43 Few other attempts to selectivel
Page 65 and 66: 45 The second phenol ether 36 was f
Page 67 and 68: 47 The enantiomeric purity was chec
Page 69 and 70: 49 A second purpose of this derivat
Page 71 and 72: 51 substrates considered. In conseq
Page 73 and 74: 53 Single-crystal X-ray analysis of
Page 75 and 76: 55 To convert atropisomer Ia into I
Page 77 and 78: 57 This finally allows one to use t
Page 79 and 80: the steric bulk and charge delocali
Page 81 and 82: 61 To check the reproducibility of
Page 83: 63 Figure 9. Full lineshape analysi
Page 86 and 87: 66 suitably substituted dilithiobip
Page 89: Experimental Part
Page 92 and 93: 70 deuterochloroform (CDCl3) unless
Page 94 and 95: 72 1 H NMR: δ = 7.32 (dddd, J = 9,
Page 96 and 97: 1 H NMR: δ = 6.96 (s, 3 H), 6.94 (
Page 98 and 99: 76 C21H21O9P (448.36) calcd. C 56.2
Page 100 and 101: 78 C12H12BrN (250.13) calcd. C 57.6
Page 102 and 103: 80 C13H13NO2 (215.25) calcd. C 72.5
Page 104 and 105: 82 3.1.1 Dialkyl-N,N-diethylaminoph
Page 106 and 107: 84 apparatus. The solution was adde
Page 108 and 109: 86 Di-tert-butylisopropylphosphine
Page 110 and 111:
88 13 C NMR: δ = 32.9 (d, J = 12 H
Page 112 and 113:
90 13 C NMR: δ = 41.5 (d, J = 61 H
Page 114 and 115:
31 P NMR: δ = 53.4 ppm. 92 C16H31O
Page 116 and 117:
94 13 C NMR: δ = 40.8 (d, J = 3 Hz
Page 118 and 119:
96 31 P NMR settings: It is known t
Page 120 and 121:
98 Theoretical ratio: (96.1:3.9) Ex
Page 123 and 124:
101 4 The Preparation and Racemate
Page 125 and 126:
103 extraction protocol with ethyl
Page 127 and 128:
105 extracted with ethyl acetate (2
Page 129 and 130:
107 (+)-(M)-Dimethyl-6,6’-dibromo
Page 131 and 132:
109 (+)-(M)-2,2’-Dibromo-6,6’-b
Page 133 and 134:
111 1 H NMR: δ = 7.2 (m, 20 H), 7.
Page 135 and 136:
113 2,2’-Dilithio-6,6’-bis(meth
Page 137:
References
Page 140 and 141:
116 Conference Proceedings, Naples,
Page 142 and 143:
118 [ 70] J. Drowart, C.E. Myers, R
Page 144 and 145:
120 [117] S.T. Graul, R.R. Squires,
Page 146 and 147:
122 [170] B.H. Lipshutz, F. Kayser,
Page 148:
124 [212] M. Schlosser, in Organome
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O P 27i: p. 30, 80 C 9H 21OP P 26b:
Page 156:
P P P O 2: p. 11, 59 3 P O O O 11:
Page 160:
Nom Maurin Prénom Michaël 129 Cur
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My PhD dissertation - Institut Fresnel

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