My PhD dissertation - Institut Fresnel

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48 Another advantage of the synthetic route chosen in this work was pointed out whilst comparing these results with those published by R. Schmid et al. [15] . As a matter of fact, R. Schmid et al. described the preparation of diol 39 in its racemic form only, starting from 2-bromoaniline and with an overall yield ranging 24%. In our case, the use of diacid 37 allowed the preparation of both enantiomerically pure atropisomers of 39 with a significant gain in overall yield (38% and 36% depending on the isomer). Finally, diol 39 was converted to the corresponding 2,2’-dibromo-6,6’-bis(methoxymethyl)biphenyl (41) in 93% yield, by treatment with sodium hydride in tetrahydrofuran followed by addition of iodomethane at 25 °C. Br Br (P)-(-)-39 OH OH NaH (2.0 eq.) THF, 25 °C, CH 3I Br Br O O (P)-(-)-41, 93% The transformation of 39 into its dimethyl ether derivative 41 was steered by a twofold motivation. First of all, after treatment of bisether 41 with a phosphorylating reagent, the resulting bisphosphine could be used as a chiral ligand for enantioselective hydrogenations or isomerizations of various substrates. The results obtained with ruthenium or rhodium catalyzed reaction could be compared with those described for MeO-BIPHEP [16] , its phenolic equivalent. Several research groups independently studied the effect of phosphine basicity on a catalytic process [ - ] 192 194 . They could show that slight variation of this parameter can induce tremendous increases in the reaction rates and turnover frequencies (tof), and even branched to linear isomers ratio in some particular cases of asymmetric hydroformylations. Thus, changing the phenol ether in compound 35 for its alcohol equivalent 41 was thought to change the electronic properties of the biaryl unit and, consequently, the basicity of the corresponding phosphine. Furthermore, since addition of one carbon atom in the ethereal chain was expected to increase the steric bulk at both ortho- positions of the biphenyl unit, it could slightly modify the dihedral angle of the corresponding bisphosphine thus, its bite angle (β) in the metal complex. The intimate relationship between dihedral angle in a chiral atropisomeric bisphosphine and the enantioselectivity of the metal catalyzed reaction involved was shown by X. Zhang et al. [18] who prepared a series of conformationally rigid bisphosphines with defined bite angles (TunaPhos).
49 A second purpose of this derivatization was to make the most of the diastereotopic hydrogens present in the hydroxymethyl- chain. As a matter of fact, since both methylene hydrogens of the -CH2OCH3 residue arediastereotopic, they could be utilized as probes for dynamic 1 H-NMR experiments, in order to determine coalescence parameters. Therefore, it seemed important to protect the free alcohol functions to allow a coalescence study of 2,2’- dilithio-6,6’-bis(methoxymethyl)biphenyl without any intramolecular reduction of the lithio- species formed or aggregation interference. 4.3 Preparation of Biphenylbisphosphines The enantiomerically pure dibromobiphenyl derivatives were converted via the dilithio intermediates to the corresponding bis(diphenylphosphines). Contrary to the first double bromine/lithium permutation process, this last step required optimization of the reaction conditions. As a matter of fact, a first attempt using the same conditions as previously, led to a mixture of mono- and bisphosphine. Since the low solubility of the monolithiated species was believed to account for the mixture obtained, various solvents were tried. The double permutational bromine/lithium exchange was finally fully achieved with two equivalents of butyllithium in an 8 : 2 mixture of toluene and diethyl ether at - 40 °C for 1 h. The use of four equivalents of tert-butyllithium instead of simple butyllithium, in tetrahydrofuran afforded the same results within 10 min at -75 °C. Another remaining problem which had to be envisaged while treating various 2,2'dilithiobiphenyl derivatives with chlorodiphenylphosphine, was the possible formation of the corresponding "phenyl-9-phosphafluorene" (phenyl-5H-benzol[b]-phosphindole) as reported [ ] by T.K. Miyamoto et al. 195 in the case of simple 2,2'-dilithiobiphenyl. The formation of the unexpected 9-phenyl-9-phosphafluorene was reinvestigated by O. Desponds and [ ] M. Schlosser 196 , who postulated a concerted mechanism for the cyclization process and subsequent formation of triphenylphosphine. However, this mechanism seems possible provided that the Phenyl–P and Li–biphenyl bonds are either coaxial or close enough to interact during free rotation around the biphenyl single bond, which would imply a relatively small dihedral angle of the biphenyl unit. This undesired side reaction was in fact avoided by slow addition of a diluted solution of chlorodiphenylphosphine to the lithiated species in order to maintain the temperature below- 70 °C, thus "freezing" rotation about the biphenyl sp 2 -sp 2 pivot bond.
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 and 60: 39 4 A Novel Access to Atropisomeri
Page 61 and 62: 41 Since the homocoupling of the ha
Page 63 and 64: 43 Few other attempts to selectivel
Page 65 and 66: 45 The second phenol ether 36 was f
Page 67: 47 The enantiomeric purity was chec
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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