My PhD dissertation - Institut Fresnel

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N (S)-14 1) NBS, THF, - 75 °C 2) - 75 °C to 25 °C 16 Br N N Br + Br (S)-17, 71% 98 : 2 (S)-18 Pure bromopyrrole (17) was then submitted to bromine/lithium permutation with butyllithium at - 75 °C and treated with 1/3 equivalent of triethyl phosphite. 1 H NMR and thin layer chromatography analysis of the crude resulting reaction mixture showed the presence of a mixture of mono-, di-, and trisubstituted phosphines, the major product being the ethyl bis{N-[(1S)-phenylethyl]pyrrol-2-yl} phosphinite (19) which could hardly be separated from the other phosphine and phosphinite. In view to this result, a second attempt was tried and aimed at preparing the phosphinite (19) selectively. Thus, the transient lithiated pyrrole generated with butyllithium in toluene at 0 °C was added to 1/2 equivalent of triethyl phosphite at - 75°C in order to prepare the dipyrrolyl phosphinite (19) exclusively. This last reaction still gave a mixture of the different substitution pattern products, but in much smaller proportions and allowed a column chromatography isolation of phosphinite (19) in 47% yield. Although characterization of the desired product was effected by 1 H, 13 C and 31P NMR, all attempts of further purifications to provide analytically pure material for elemental analysis failed. Further attempts to convert phosphinite (19) into a crystalline derivative by means of phenyllithium resulted in no reaction, probably due to steric hindrance around the phosphorus atom. Br N (S)-17 1) LiC 4H 9, Toluene, 0 °C 2) P(OC 2H 5) 3 (0.5 équiv.) O P N (S,S)-19, 47% As in the case of binaphthyl phosphinite (5), the phosphinite (19) obtained was believed to be an interesting phosphorylating reagent for preparing chiral ligands and would be an alternative to chiral phosphine where the phosphorus atom is bearing the chiral information [72, 73] . As a more efficient and convenient access to phosphinite (19) was sought, the more robust and easily purified 2-chloro-N-(1-phenylethyl)pyrrole (20) was prepared in an almost quantitative way by reproducing the previously described selective mono-halogenation conditions with N-chlorosuccinimide (NCS). Chlorination of the pyrrole (14) in tetrahydrofuran at - 75 °C was much slower than its bromination 2
17 and gave only the mono-chlorinated pyrrole at the 2-position in 74% after distillation. Gas chromatography analysis of the crude reaction mixture revealed the presence of the expected chloropyrrole (20) together with a by-product in a 4 : 1 ratio. This latter product could be isolated as crystalline material in 11% and was identified as the N-{1- [(1S)-phenylethyl]pyrrol-2-yl} succinimide (21) stemming from the addition of succinimide on the chloropyrrole (20). N (S)-14 1) NCS, THF, - 75 °C 2) - 75 °C to 25 °C Cl N + N N (S)-20, 74% (S)-21, 11% The standard Grignard reaction conditions applied to chloropyrrole (20) in tetrahydrofuran with commercial magnesium turning did not produce any trace of organometallic species. Conditions were then varied by changing solvents or reaction temperatures, and the formation of the Grignard reagent was followed by gas chromatography after trapping of an aliquot with carbon dioxide and subsequent esterification with diazomethane. Since only small amounts of Grignard species could be formed this way, several activated magnesium were tried [ ] 102 before R.D. Rieke's conditions O O [ ] 103 revealed effective and afforded the expected enantiomerically pure N-[(1R)-phenylethyl]pyrrole-2- carboxylic acid (22) in 74% after crystallization although this yield was determined to be of 97% by gas chromatography when the reaction was ran with an internal calibrated standard. Cl N (S)-20 1) K, MgCl 2, KI, reflux ClMg N 2) CO 2, THF 3) HCl 10% HOOC N (S)-22, 74% These conditions to produce the active magnesium chloride species were then applied for the preparation of the phosphinite (19). Unfortunately, the same generated Grignard reagent, when treated with 1/2 equivalent of triethyl phosphite gave only lower yields of less pure product due to the difficulty to remove the magnesium salts. Few more trials with other phosphites resulted either in lower reaction rate in the case of triphenyl phosphite or in the formation of the corresponding methyldipyrrolylphosphine oxide presumably by Michaelis-Arbuzov rearrangement as already encountered by H. Gilman and J. Robinson [ ] 104 .
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 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 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
Page 152:
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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