My PhD dissertation - Institut Fresnel

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42 trace of organic byproducts, as suggested by a correct mass balance and 1 H-NMR of the crude product, it was used without any purification for the preparation of derivatives in the racemic series. On the other hand, as the only impurities in the crude product were believed to be essentially boron salts, the analytically pure racemic material was utilized for the racemate resolution step. Br Br LiC 4H9 (2.0 eq.) Br Br THF, - 75 °C Br Li Br Li 1) FB(OCH 3) 2, DEE, - 75 °C 2) NaOH 2.O M, 0 °C 3) H 2O 2 35%, 0 °C Br OH Br OH 30 rac-31, 76% 4.1.2 Racemate Resolution of 6,6’-Dibromobiphenyl-2,2’-diol Several methods were examined to resolve the axially chiral biphenol 31. The first trial relying on a well established protocol was the conversion of the biphenol into a cyclic phosphate derivative and subsequent treatment with cinchonine to separate the two diastereomeric salts [ ] 179 . Unfortunately, the low solubility of the biphenol-based cyclic phosphate rendered this protocol practically not viable. A promising method described by G. Delogu et al. [ ] 180 was also applied to biphenol 31. Its conversion to the corresponding diastereomeric dicarbonate, by means of (1R,2S,5R)-(-)-menthylchloroformate was effectively performed in good yield. However, the racemic mixture 32 did not show a sufficiently high difference in retention factor (Rf) to be properly resolved by column chromatography, even with several different eluent solvent systems and either on silica or basic alumina. Br OH Br OH rac-31 (-)-menthylchloroformate (2.0 eq.) N(C 2H 5) 3, CH 2Cl 2, 25 °C O Br O O Br O O R * R * O 32, 86% R * =
43 Few other attempts to selectively crystallize either inclusion complex with N-benzylcinchonidinium chloride pseudoephedrine [ , ] 181 182 , or diastereomeric salts with (1R,2R)-(-)- [ ] 183 remained ineffective. The resolution of biphenol 31 was ultimately achieved by its treatment with (1R,2R)-(-)-1,2-diaminocyclohexane (DACH) (33) in an ethanol/hexanes mixture. Thus, both (+)-31·(-)-33 and (-)-31·(-)-33 inclusion complexes separately by fractional crystallization [ ] 184 . Simple hydrolysis of each diastereomeric complex then gave the pure enantiomers in good yield (39 to 42%). Enantiomeric excess (ee) were checked by conversion of each pure isomer of biphenol 31 into their corresponding methyl phenol ether and then into MeO-BIPHEP [16] . Comparison of the [ ] 20 rotatory power α measured with that reported by R. Schmid et al. in the same conditions, gave ee ≥ 99% (see § 4.3.1). D This resolution method was not only practically easy going, but also had the advantage to use an inexpensive resolving agent. Indeed, although pure (1R,2R)-(-)-DACH 33 was costly, it was possible to use the cheap racemic 33 and resolve it with the commercial L- (+)-tartaric acid. Furthermore, the chiral amine could be quantitatively recovered as its L-(+)- tartrate salt as described by Gilheany et al. Br Br rac-31 OH OH H 2N H 2N (R,R)-(-)-33 Ethanol/Hexanes (9:1), reflux Precipitate Mother liquors [ ] 185 . Br Br OH OH Br OH Br OH . . H 2N H 2N (P)-(-)-31 . (R,R)-(-)-33 H 2N H 2N (M)-(+)-31 . (R,R)-(-)-33 4.1.3 Derivatization of 6,6’-Dibromobiphenyl-2,2’-diol 10% aq.HCl 10% aq.HCl Br Br OH OH (P)-(-)-31, 39% Br OH Br OH (M)-(+)-31, 42% The biphenol thus resolved was either O-protected or the two remaining bromines were directly replaced by phosphino groups. Since the ortho- and ortho'- substituents on the biphenyl core do not only affect its electronic properties but also the steric hindrance to rotation, it was possible to control the dihedral angle of the biphenyl unit by varying the steric
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: 41 Since the homocoupling of the ha
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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