Supporting Information
of
Chemically Triggered C—ON Bond Homolysis in Alkoxyamines. Part 7. Remote Polar
Effect.
Gérard Audran, Matisse bim Batsiandzy Ibanou, Paul Brémond, Sylvain. R. A. Marque,*
Germain Obame, Valérie Roubaud and Didier Siri
Université d’Aix-Marseille CNRS– UMR 7273, case 551, Avenue Escadrille NormandieNiemen, 13397 Marseille cedex 20. E-mail: sylvain.marque@univ-amu.fr
1. Preparation of compounds 2b-g
2
2. Optimization of structures by DFT
7
3. Figures 1SI and 2SI
23
1
1. Preparation of compounds 2b-g
General information
All corresponding glassware was oven-dried (80 °C). All solvents were used as received.
Routine monitoring of reactions was performed using Merck Silica gel 60 F254, aluminum
supported TLC plates; spots were visualized using UV light and ethanolic acidic paraanisaldehyde solution or ethanolic phosphomolybdic solution, followed by heating. 1H,
and
13
C
31
P NMR spectra were recorded in CDCl3 solutions on 300 or 400 MHz spectrometers.
Chemical shifts (δ) in ppm are reported using residual non-deuterated solvents as internal
reference. Min and Maj stand for minor (SS/RR) and major (SR/RS) diastereomers,
respectively, as reported.1,2 High resolution mass spectra (HRMS) have been performed using
a mass spectrometer equipped with a pneumatically assisted atmospheric pressure ionization.
The mass spectrum was obtained using a time of flight analyzed (ToF). The measure was
realized in triplicate, with double internal standardization. The sample was dissolved in
CH2Cl2 (400 µL) then diluted (dilution factor 1/104) in a methanolic solution of ammonium
acetate (3 mM). The sample solution was infused in the ionization source at a 10 µL/min flow
rate. Compound 1 was synthesized as 2:1 mixture of diastereomers according to the
literature.1,2 N,N,N-dimethyl-para-bromomethylphenylammonium bromide was prepared as
described.3
Typical Procedure for the preparation of 2b-g. To a stirred solution of 1 (500 mg, 1.3
mmol) in THF (12.5 mL) was added para-subsituted benzyl bromide (187 µL, 1.5 mmol)
2
except for 2f. The resulting mixture was stirred at room temperature under argon for 24h. It
was then concentrated in vacuo and triturated with an ether/pentane mixture to yield the
targeted alkoxyamine as oil.
4-(1-(N-tert-butyl-N-[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]-aminooxy)-ethyl)-1(4-fluorobenzyl)-pyridinium, bromide (2b): 1H NMR (400 MHz, CDCl3, mixture of
rotamers): δ = 9.9 (br.s, 2H, min), 9.6 (d, J = 4.8 Hz, 2H, Maj), 8.4 (br.s, 2H, min), 7.9 (d, J =
4.8 Hz, 2H, Maj), 7.8 (m, 4H, min), 7.7-7.6 (m, 2H, min and Maj), 7.1-7.0 (m, 2H, min and
Maj), 6.5 (br s, 2H, min), 6.5 (br.s, 2H, Maj), 5.3 (q, J = 6.5 Hz, 1H, Maj), 5.1 (m, 1H, min),
4.3-4.1 (m, 2H, min), 4.0-3.9 (m, 2H, min), 3.9-3.8 (m, 2H, Maj), 3.6-3.6 (m, 2H, Maj), 3.5
(s, 1H, Maj), 3.4 (s, 1H, min), 1.6 (d, J = 6.8 Hz, 3H, min), 1.5 (d, J = 6.7 Hz, 3H, Maj), 1.2
(s, 3H, Maj), 1.2-1.1 (s, 12H, min and Maj), 1.1 (s, 11H, min and Maj), 1.0 (t, J = 7.0 Hz, 3H,
Maj), 0.8 (s, 9H, min).
13
C NMR (400 MHz, CDCl3, mixture of rotamers): δ = 193.1, 164.4,
164.2, 163.2, 163.02, 161.9, 147.7, 146.7 (m), 141.9, 141.1, 137.4, 134.5, 131.8 (d, J = 8.8
Hz), 131.4, 128.1, 125.8, 124.8, 116.4, 116.4 116.2, 116.1, 109.9, 92.1, 65.3, 63.2, 62.4, 62.1,
61.9, 61.5, 61.0, 34.7, 30.2 (d, J = 5.8 Hz), 28.1 (d, J = 2.2 Hz), 27.7, (d, J = 5.1 Hz), 27.1 (d,
J = 3.7 Hz), 26.9, 24.7, 23.8 (d, J = 2.9 Hz), 23.9, 15.8 (d, J = 9.6 Hz), 15.6 (m), 14.7.
31
P
NMR (400 MHz, CDCl3): δ = 24.8 (min), 23.9 (Maj). HRMS (ESI) m/z calcd for
C27H43N2O4FP1 (M)+ 509,2939, found 509,2937.
4-(1-(N-tert-butyl-N-[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]-aminooxy)-ethyl)-1(4-cyanobenzyl)-pyridinium, bromide (2c): 1H NMR (400 MHz, CDCl3, mixture of
rotamers): δ = 10.1 (br.s, 2H, min), 9.6 (d, J = 5.0 Hz, 2H, Maj), 8.4 (br.s, 2H, min), 8.0 (d, J
= 5.0 Hz, 3H, min and Maj), 7.9 (d, J = 8.0 Hz, 3H, min and Maj), 7.7 (m, 3H, min and Maj),
3
6.6 (br s, 2H, min), 6.5 (br.s, 2H, Maj), 5.3 (q, J = 6.5 Hz, 1H, Maj), 5.1 (m, 1H, min), 4.3-4.2
(m, 2H, min), 4.1-4.0 (m, 2H, min), 3.9-3.8 (m, 2H, Maj), 3.6-3.5 (m, 2H, Maj), 3.4 (s, 1H,
Maj), 3.3 (s, 1H, min), 1.6 (d, J = 6.5 Hz, 3H, min), 1.5 (d, J = 6.8 Hz, 3H, Maj), 1.2 (s, 3H,
Maj), 1.2 (s, 12H, min and Maj), 1.1 (s, 14H, min and Maj), 0.9 (s, 9H, min). 13C NMR (400
MHz, CDCl3, mixture of rotamers): δ = 192.9, 192.1, 167.8, 164.2, 148.1, 137.7, 137.1,
132.8, 132.7, 130.5, 129.7, 126.5, 126.1, 125.5, 117.4 (d, J = 3.7 Hz), 113.6, 110.0, 92.6,
90.3, 83.4, 65.4, 61.9, 61.8, 61.6 (d, J = 4.9 Hz), 60.2, 34.9, 30.7 (d, J = 5.8 Hz), 28.1, 27.7 (d,
J = 5.2 Hz), 26.9, 24.8, 23.6, 21.5, 15.9-15.6 (m), 15.3. 31P NMR (400 MHz, CDCl3): δ = 24.8
(min), 23.9 (Maj). HRMS (ESI) m/z calcd for C28H43N3O4P1 (M)+ 516.2986, found 516.2985.
4-(1-(N-tert-butyl-N-[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]-aminooxy)-ethyl)-1(4-methoxybenzyl)-pyridinium, bromide (2d): 1H NMR (400 MHz, CDCl3, mixture of
rotamers): δ = 9.99 (br.s, 2H, min), 9.56 (d, J = 4.8 Hz, 2H, Maj), 7.99 (d, J = 4.8 Hz, 2H,
Maj), 7.88 (m, 4H, min), 7.75 (m, 2H, Maj), 7.05 (m, 3H, min and Maj), 6.47 (br s, 2H, min),
6.34 (s, 2H, Maj), 5.33 (q, J = 6.8 Hz, 1H, min and Maj), 4.09-3.99 (m, 2H, min), 3.93-3.88
(m, 2H, Maj), 3.75-3.70 (m, 2H, min), 3.66-3.63 (m, 2H, Maj), 3.46 (s, 1H, Maj), 3.40 (s, 2H,
min), 1.60 (d, J = 6.8 Hz, 3H, min), 1.55 (d, J = 6.8 Hz, 3H, Maj), 1.36-1.32 (m, 6H, min),
1.20 (s, 15H, Maj), 1.10 (s, 9H, min and Maj), 1.07 (s, 9H, min), 0.88 (s, 9H, min). 13C NMR
(400 MHz, CDCl3, mixture of rotamers): δ = 162.6, 160.4, 160.3, 146.7, 144.1, 143.5, 131.3,
131.1, 130.9, 130.8, 125.8, 125.4, 125.1, 125.0, 124.9, 124.7, 124.4, 114.5-114.4 (m), 69.4,
68.0, 66.8, 65.4, 62.7, 61.5, 61.0 (d, J = 7.3 Hz), 59.6 (d, J = 7.3 Hz), 54.9, 35.2 (d, J = 5.1
Hz), 34.8 (d, J = 4.4 Hz), 30.3 (d, J = 5.9 Hz), 29.7, 28.3, 27.7, 20.9, 15.9-15.7 (m), 14.8. 31P
NMR (400 MHz, CDCl3): δ = 25.3 (min), 24.1 (Maj). HRMS (ESI) m/z calcd for
C28H46N2O5P1 (M)+ 521.3139; found 521.3138.
4
4-(1-(N-tert-butyl-N-[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]-aminooxy)-ethyl)-1(4-N,N-dimethylammoniumylbromide)benzyl-pyridinium, bromide (2e):
1
H NMR (400
MHz, CDCl3, mixture of rotamers): δ = 8.9 (br.s, 2H, min), 8.8 (br.s, 2H, Maj), 8.0 (br.s, 3H,
min and Maj), 7.9 (br.s, 3H, min), 7.8 (d, J = 8.0 Hz, 2H, Maj), 7.7 (d, J = 7.9 Hz, 2H, min),
7.5 (d, J = 7.8 Hz, 2H, Maj), 6.4 (br.s, 2H, min and Maj), 5.3 (q, J = 6.5 Hz, 1H, min and
Maj), 4.1-4.0 (m, 4H, min), 3.9-3.8 (m, 2H, Maj), 3.7-3.6 (m, 2H, Maj), 3.4 (s, 1H, min and
Maj), 3.2 (s, 6H, Maj), 3.1 (s, 6H, min), 1.6 (d, J = 6.2 Hz, 2H, min), 1.6 (d, J = 6.5 Hz, 3H,
Maj), 1.3 (s, 6H, Maj), 1.2 (s, 9H, Maj), 1.1 (s, 6H, min), 1.1 (s, 9H, Maj), 1.0 (s, 9H, min),
0.8 (s, 9H, min). 13C NMR (400 MHz, CDCl3, mixture of rotamers): δ = 164.5, 148.2, 147.8,
141.6, 140.2, 130.8, 129.1, 124.9, 120.7, 120.5, 77.4, 77.1, 73.2, 71.8, 69.8, 67.9, 62.6 (d, J =
6.3 Hz), 61.4 (d, J = 7.0 Hz), 61.2 (d, J = 8.1 Hz), 58.3, 46.8, 46.7, 35.1 (d, J = 6.1 Hz), 28.4
(d, J = 8.8 Hz), 27.9, 27.9, 27.4 (d, J = 3.3 Hz), 21.3, 16.1-15.9. 31P NMR (400 MHz, CDCl3):
δ = 25.0 (min), 24.2 (Maj). HRMS (ESI) m/z calcd for C29H49N3O4P1 (M)+ 534.3455, found
534.3450.
4-(1-(N-tert-butyl-N-[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]-aminooxy)-ethyl)-1(4-dimethylaminobenzyl)-pyridinium, bromide (2f): To stirred solution of 2e (500 mg,
0.72 mmol) in 1.1 CH2Cl2 /H2O (14 ml) was added Na2CO3 (79.5 mg, 0.54 mmol). The
resulting mixture was stirred at room temperature for 30 min. The aqueous layer was
extracted with CH2Cl2, then the organic layers were combined ,wash brine, dried over MgSO4
and evaporated to furnish 2f (362 mg, 82% yield) as a black oil. 1HNMR (400 MHz, CDCl3,
mixture of rotamers) : δ = 8.7 (br,s, 2H, min), 8.1 (br,s, 2H, Maj), 7.8 (d, J = 8.34 Hz,2H,
min), 7.7 (d, J = 8.5 Hz, 2H Maj), 7.51 (d, J = 8.7 Hz, 2H, min), 7.45 (d, J = 8.7 Hz, 2H,
5
Maj), 6.3 (br,s,2H, min and Majo), 5.33 (q, J = 6.6 Hz 1H, min and Maj), 4.1-4.06 (m, 4H,
min), 3.8-3.7 (m, 2H, Maj), 3.7-3.6 (m, 2H, Maj), 3.5 (s, 1H, min and Maj), 3.4 (s, 6H, Maj),
3.3 (s,6H, Min), 1.5 (d, j = 6.6 Hz, 3H, min), 1.4 (d, J = 6.3 Hz, 3H, Maj) 1.3 (s, 6H, Maj), 1.2
(s, 9H, Maj), 1.1 (s, 6H, min), 1.1 (s, 9H, Maj); 0.9 (s, 9H, min) 0.8 (s, 9H, min).
13
C NMR
(400 MHz, CDCl, mixture of rotamers):δ = 152.2, 150.7, 150.3, 149.7, 148.7, 143.8, 130.3,
128.7, 125.3, 122.02, 111.02, 76,7, 72.1, 70,1,68.2, 64.5, 62.02 (d, J = 6.05 Hz), 61.4 (d, J =
6.04 Hz), 61.04 (d, J = 5.51 Hz) 58.7 (d, J = 7.7 Hz), 53.09, 40.1, 39.6, 34.8 (d, J = 4.95 Hz),
30.2 (d, J = 6.06 Hz), 28.1 (d, J = 3.3 Hz), 27.6, 27.2 (d, J = 3.85 Hz), 30.72, 15.90-15.61 (m),
14.75.
31
P NMR (162 MHz, CDCl3) : δ = 24.73 (min), 23.46 (Majo). HRMS ESI m/Z calcd
for C29H49N3O4P1 (M)+ 534.3455; Found 534.3458
4-(1-(N-tert-butyl-N-[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]-aminooxy)-ethyl)-1(4-nitrobenzyl)-pyridinium, bromide (2g):
1
H NMR (400 MHz, CDCl3, mixture of
rotamers): δ = 10.17 (br.s, 2H, min), 9.7 (d, J = 4.5 Hz, 2H, Maj), 8.2-8.1 (m, 4H, min and
Maj), 8.1-8.0 (m, 4H, min and Maj), 6.7 (br s, 2H, min), 6.6 (br.s, 2H, Maj), 5.3 (q, J = 7.0
Hz, 1H, min and Maj), 4.1-4.0 (m, 2H, min), 3.9-3.8 (m, 3H, min and Maj), 3.7-3.6 (m, 2H,
Maj), 3.5 (s, 1H, Maj), 3.4 (s, 1H, min), 1.6 (d, J = 6.5 Hz, 3H, min), 1.5 (d, J = 6.5 Hz, 3H,
Maj), 1.2 (s, 3H, Maj), 1.2-1.1 (s, 15H, min and Maj), 1.1 (s, 10H, min and Maj), 1.0 (m, 3H,
Maj), 0.8 (s, 9H, min).
13
C NMR (400 MHz, CDCl3, mixture of rotamers): δ = 193.0, 163.6,
148.2, 148.2 (d, J = 3.7 Hz), 146.6 (d, J = 6.6 Hz), 139.7, 139.1, 130.9, 130.4, 129.4, 126.0,
125.6, 124.9, 124.0 (d, J = 10.3 Hz), 123.5, 109.9, 69.2, 67.8, 65.3, 61.5, 61.2, 61.0 (d, J = 8.1
Hz), 59.6 (d, J = 7.3 Hz), 34.7 (d, J = 4.4 Hz), 30.1 (d, J = 5.8 Hz), 28.1, 28.0, 27.6, 27.1,
26.9, 23.9, 23.6, 20.9, 15.9-15.6 (m), 14.7. 31P NMR (400 MHz, CDCl3): δ = 24.7 (min), 23.9
(Maj). HRMS (ESI) m/z calcd for C27H43N3O6P1 (M)+ 536.2884, found 536.2882.
6
2. Optimization of structures, Mulliken and NBO charges by DFT
All calculations were performed using Gaussian package 09, revision A02.4 The geometry of
the species were optimized at the B3LYP/6-31G(d,p) level of theory. Vibrational frequencies
calculated at B3LYP/6-31G(d,p) level to insure that the obtained geometries are minima (no
imaginary frequency). The vibrational frequencies were scaled by a usual factor of 0.9608.
The corresponding thermal corrections were included to obtain the enthalpy and Gibbs free
energy values under the standard conditions (p = 1 atm and T = 298.15 K). Values are given
in u.a.
Table 2SI. Selected calculated geometrical parameters (bond length l, distance d, valence
angle , and torsion angle ) by DFT at B3LYP/6-31G(d,p) level.
2a
2d
2g
2h
2i
O1–C13
1.433
1.433
1.432
1.434
1.426
N2–O1
1.466
1.466
1.467
1.465
1.470
bond length l (Å)
7
C3–P6
1.877
1.877
1.878
1.878
1.876
P6–O7
1.492
1.492
1.492
1.492
1.493
N2•••••C13
2.410
2.410
2.408
2.411
2.404
O7••••C16
5.144
5.193
5.17
5.17
5.083
<N2O1C13>
112.48
112.46
112.33
112.56
112.17
<C3N2O1>
108.77
108.76
108.85
108.79
108.58
<O1C13C16C14>
-120.41
-120.40
-120.30
-120.23
-120.28
<N2O1C13H15>
5.66
7.23
7.31
7.20
4.79
<C13O1N2n,N8>a
1.17
1.82
1.97
1.39
1.64
<O7P6C3N2>
85.90
87.60
86.70
88.65
83.94
<C16C13O1N2>
-114.23
-112.49
-112.43
-112.65
-115.46
<C18N19C20C21>
145.15
157.53
46.37
-162.23
69.08
<N19C20C21C22>
106.03
98.97
69.28
83.05
45.13
distance d (Å)
valence angle  (º)
torsion angle 
a
<nNOC> = <C3N2O1C13> – 120°.
8
2a
ZPE = 0.654680
E = -1806.289533
H = -1806.288588
G = -1806.403384
C
-3.042826 -0.765204
0.226607
H -3.638335 -0.695990
1.140583
C
-3.796690 -1.821803
-0.694096
C
-3.814411 -3.187625
0.021407
H -4.316170 -3.921966
-0.616679
H -4.363628 -3.147249
0.967081
H -2.803428 -3.550423
0.219960
C
-3.150998 -2.017482
-2.078335
H -2.151513 -2.455490
-2.003513
H -3.095793 -1.081681
-2.635846
H -3.757126 -2.722172
-2.657070
C
-5.266287 -1.394156
-0.908621
H -5.354531 -0.520720
-1.557274
9
H -5.769021 -1.166079
0.035742
H -5.806924 -2.216841
-1.386993
C
-5.241042
2.607106
-0.254138
H -5.208002
2.737716
-1.340322
H -4.648404
3.400942
0.213340
C
-6.664435
2.602479
0.266816
H -7.248292
1.805794
-0.201592
H -7.143832
3.559725
0.040160
H -6.681949
2.456551
1.350313
C
-1.169882
2.755340
-0.016083
H -1.169203
2.706718
-1.108126
H -0.247801
2.293953
0.355892
C
-1.299950
4.184580
0.479846
H -2.202080
4.656262
0.080743
H -0.436032
4.772872
0.152961
H -1.346609
4.217983
1.571887
C
-1.353145 -1.236042
2.097853
C
-2.357201 -2.154619
2.822465
H -3.382929 -1.781582
2.794778
H -2.068669 -2.207672
3.875850
H -2.344792 -3.167929
2.417673
C
-1.360206
0.149483
2.766769
H -0.649835
0.825335
2.287818
H -1.077238
0.044886
3.819177
H -2.344330
0.620529
2.731362
10
C
0.035092
-1.879259
2.259884
H
0.097165 -2.816736
1.698140
H
0.214342 -2.104119
3.314960
H
0.832332
-1.212220
1.931171
C
0.056975
-1.048110
-1.050623
H -0.366282 -2.049111
-1.158923
C
1.522973
-1.169326
-0.679216
C
2.195344
-0.147491
0.009632
H
1.649856
0.716483
0.369242
C
3.553288
-0.234883
0.237950
H
4.118510
0.533988
0.749214
C
3.643438
-2.311144
-0.852803
H
4.266845 -3.141468
-1.162330
C
2.286945
-2.264872
-1.107928
H
1.828691 -3.087685
-1.645981
C
-0.021202 -0.273747
-2.379411
H -1.063731 -0.073007
-2.626551
H
0.452420 -0.842762
-3.185492
H
0.492340
0.688727
-2.293216
N -1.674210 -1.216386
0.617548
N
4.264198 -1.305746
-0.192115
O -2.893351
1.168403
-1.903674
O -2.274336
1.977193
0.495139
O -4.635882
1.327836
0.081164
O -0.687423 -0.355332
-0.041449
11
P
-3.148306
0.984917
-0.444882
C
5.741988
-1.417503
0.114002
H
5.820245
-1.869107
1.106656
H
6.137460 -2.127185
-0.615368
C
6.471151
-0.101609
0.053959
C
6.876753
0.532318
1.235625
C
6.762807
0.491845
-1.183390
C
7.561657
1.747663
1.182464
H
6.671889
0.069259
2.197753
C
7.443050
1.706141
-1.234147
H
6.465543
0.000693
-2.106653
C
7.842130
2.335130
-0.051226
H
7.880071
2.228448
2.101670
H
7.671203
2.157621
-2.194249
H
8.378280
3.277796
-0.093772
12
2d
ZPE = 0.686021
E = -1920.784109
H = -1920.783165
G = -1920.904040
C
-3.602389 -0.600096
0.281820
H -4.154210 -0.451442
1.213203
C
-4.476460 -1.622759
-0.568804
C
-4.560314 -2.962584
0.189896
H -5.144870 -3.674947
-0.400865
H -5.058717 -2.855136
1.158032
H -3.569913 -3.393778
0.353161
C
-3.919519 -1.907240
-1.976550
H -2.954973 -2.421511
-1.937529
H -3.818870 -0.994609
-2.565171
H -4.607910 -2.577365
-2.502002
C
-5.918459 -1.088609
-0.725777
H -5.972144 -0.224359
-1.390545
H -6.356709 -0.804523
0.235525
H -6.541639 -1.877269
-1.159038
13
C
-5.543819
2.923163
-0.199807
H -5.565991
3.011858
-1.290508
H -4.867498
3.686074
0.200713
C
-6.930508
3.046839
0.399822
H -7.598574
2.280488
-0.001949
H -7.349570
4.029078
0.160910
H -6.894930
2.942742
1.487679
C
-1.449149
2.724133
-0.227795
H -1.521750
2.625873
-1.313977
H -0.553668
2.191876
0.113017
C
-1.414099
4.180180
0.201278
H -2.293291
4.716774
-0.165772
H -0.522783
4.668024
-0.207214
H -1.386180
4.267510
1.290994
C
-1.884984 -1.126213
2.108422
C
-2.923948 -1.941475
2.904234
H -3.921418 -1.497587
2.894485
H -2.602289 -1.974101
3.948826
H -2.996871
-2.967756
2.540337
C
-1.770338
0.282246
2.716687
H -1.039883
0.888648
2.178982
H -1.447728
0.200944
3.759757
H -2.722370
0.816458
2.703589
-0.540014 -1.859061
2.251341
C
H -0.560809
-2.817576
1.722804
14
H -0.342803 -2.059804
3.308078
H
0.289757 -1.261016
1.874275
C
-0.604270 -1.197170
-1.108193
H -1.135808 -2.148796
-1.173678
C
0.852030
-1.471666
-0.779389
C
1.666511
-0.504746
-0.172123
H
1.244122
0.438969
0.151164
C
3.011688
-0.747381
0.027443
H
3.682943 -0.030259
0.482230
C
2.810380
-2.873983
-0.941143
H
3.318995 -3.790474
-1.216635
C
1.462497
-2.675138
-1.164050
H
0.889348 -3.463173
-1.640580
C
-0.652125 -0.450790
-2.452964
H -1.679653 -0.163219
-2.677661
H -0.256005 -1.078762
-3.257152
H -0.050657
0.462220
-2.405466
N -2.261092 -1.145862
0.641397
N
3.570213 -1.918974
-0.355279
O -3.428591
1.233715
-1.929908
O -2.588741
2.081293
0.384634
O -5.017118
1.614226
0.153082
O -1.236063 -0.401916
-0.096945
P
-3.600918
1.128173
-0.451548
C
5.040475
-2.217785
-0.087885
15
H
5.058651 -2.825804
0.820773
H
5.356893 -2.843184
-0.925385
C
5.905995
-1.003318
0.052272
C
6.400340
-0.338242
-1.077185
C
6.259242
-0.518521
1.324891
C
7.216408
0.783530
-0.956321
H
6.155903 -0.703181
-2.071867
C
7.070296
0.596662
1.461949
H
5.906256 -1.029996
2.217161
C
7.557060
1.260113
0.320815
H
7.590021
1.269134
-1.849040
H
7.355859
0.971073
2.438660
O
8.340573
2.331295
0.558832
C
8.899805
3.044095
-0.545478
H
8.115898
3.472526
-1.180228
H
9.490712
3.847837
-0.107841
H
9.550575
2.398750
-1.145849
16
2g
ZPE = 0.656740
E = -2010.773029
H = -2010.772084
G = -2010.894858
C
-3.699711 -1.038780
-0.121229
H -4.474657 -1.263001
0.616328
C
-3.888280 -2.118041
-1.274966
C
-3.640670 -3.524930
-0.694054
H -3.748693 -4.267651
-1.490750
H -4.362349 -3.778538
0.088364
H -2.632846 -3.617111
-0.282758
C
-2.943133 -1.925919
-2.476475
H -1.896362 -2.089112
-2.203491
H -3.050871 -0.936830
-2.923309
H -3.183712 -2.672398
-3.240530
C
-5.340896 -2.083345
-1.802319
H -5.550469 -1.182914
-2.382527
17
H -6.073081 -2.141661
-0.991641
H -5.498522 -2.943974
-2.459772
C
-6.633829
1.657297
-0.883263
H -6.369118
1.973673
-1.896984
H -6.456573
2.491622
-0.196083
C
-8.067964
1.173110
-0.804812
H -8.237435
0.341991
-1.494318
H -8.747258
1.987831
-1.073634
H -8.311984
0.841410
0.208074
C
-2.909822
2.845749
0.341801
H -2.634114
2.916116
-0.713439
H -2.011421
2.611241
0.924855
C
-3.560442
4.125375
0.836130
H -4.436053
4.377136
0.231474
H -2.850066
4.955989
0.767179
H -3.876257
4.027363
1.878446
C
-2.412053 -1.287492
2.080608
C
-3.225252 -2.541784
2.458205
H -4.281598 -2.466431
2.192986
H -3.179544 -2.662483
3.543908
H -2.815534
-3.443296
1.999641
-2.992441 -0.066776
2.815514
C
H -2.431500
0.840559
2.585517
H -2.941237 -0.236657
3.895783
H -4.037445
2.555815
0.113227
18
C
-0.968703 -1.532270
2.552849
H -0.493792 -2.321956
1.961665
H -0.974028 -1.849282
3.599360
H -0.365252 -0.626409
2.491194
C
-0.457142 -0.319220
-0.608573
H -0.560868 -1.362883
-0.912489
C
0.864651
-0.146997
0.115916
C
1.076280
0.915725
1.009390
H
0.266544
1.592586
1.254039
C
2.313398
1.100274
1.589806
H
2.517095
1.904566
2.286325
C
3.176412
-0.765936
0.453101
H
4.045009 -1.386643
0.271953
C
1.954685
-0.989305
-0.150307
H
1.855671 -1.828585
-0.830275
C
-0.448956
0.608792
-1.836170
H -1.427167
0.580319
-2.317948
H
0.327729
0.306173
-2.545330
H -0.253797
1.642484
-1.534554
N -2.382192
-1.156263
0.572083
N
3.348633
0.268299
1.310959
O -3.672695
1.137107
-2.006680
O -3.830040
1.746432
0.519972
O -5.764975
0.555962
-0.495215
O -1.564208
0.014413
0.236879
19
P
-4.166905
0.695777
-0.669500
C
4.672685
0.461191
2.000696
H
4.728049 -0.281460
2.800742
H
4.629504
1.450126
2.461147
C
5.853644
0.342973
1.067216
C
6.733493
-0.740544
1.186593
C
6.088880
1.325578
0.093114
C
7.837031
-0.852045
0.341349
H
6.569043 -1.495931
1.949984
C
7.182596
1.223928
-0.759754
H
5.421501
2.178031
0.001592
C
8.036704
0.132042
-0.619503
H
8.534957 -1.676580
0.415965
H
7.390318
1.968380
-1.518140
N
9.202156
0.017751
-1.526949
O
9.935792 -0.953768
-1.375164
O
9.345451
-2.366002
0.901595
20
2i
ZPE = 0.670345
E = -1861.637756
H = -1861.636812
G = -1861.754770
C
-3.178806
0.612346
-0.622122
H -3.587720
0.252698
-1.569860
C
-4.064570
1.874956
-0.230706
C
-3.880974
2.970151
-1.300788
H -4.476621
3.846176
-1.025108
H -4.221977
2.640968
-2.287011
H -2.837395
3.283722
-1.378638
C
-3.715929
2.485074
1.140371
H -2.708319
2.910685
1.153636
H -3.809791
1.753823
1.944141
H -4.405170
3.310081
1.348335
C
1.490655
-0.214225
-5.561468
21
H -5.813703
0.840531
0.625359
H -5.865216
0.985636
-1.135947
H -6.159421
2.402311
-0.117547
-5.538968 -2.516308
0.415501
H -5.679950 -2.322603
1.483507
H -4.919534
-3.412262
0.299059
-6.864222 -2.665089
-0.305267
H -7.477146 -1.768224
-0.183248
H -7.414328 -3.517036
0.105955
H -6.709030 -2.838443
-1.373649
C
1.058655
C
C
-1.497495 -2.597326
H -1.710886
-2.203009
2.055429
H -0.504139 -2.252327
0.749848
C
-1.581432 -4.113092
1.027563
H -2.563192 -4.456575
1.364989
H -0.824029 -4.542451
1.691874
H -1.410202 -4.494676
0.017153
C
-1.147052
0.530576
-2.180563
C
-1.957888
1.162548
-3.329326
H -2.979727
0.783332
-3.396090
H -1.465246
0.910542
-4.272471
H -1.995195
2.250006
-3.247238
-1.080090 -0.993058
-2.384344
H -0.497431 -1.473419
-1.596685
H -0.600891 -1.208830
-3.344858
C
22
H -2.069573 -1.454503
-2.395167
C
0.271541
1.120191
-2.258340
H
0.263630
2.187415
-2.014434
H
0.659753
1.007911
-3.274489
H
0.960334
0.605715
-1.588335
C
-0.383392
1.373046
1.087811
H -0.809299
2.340527
0.814478
C
1.128069
1.445221
0.963425
C
1.906984
0.290746
0.799840
H
1.431793 -0.675368
0.679595
C
3.286111
0.373798
0.775295
H
3.932552 -0.484562
0.644449
C
3.188338
2.697810
1.070075
H
3.753580
3.617497
1.168145
C
1.808370
2.664901
1.100408
H
1.264832
3.595369
1.224470
C
-0.722435
1.019273
2.545767
H -1.797668
0.868381
2.645651
H -0.390697
1.812924
3.222514
H -0.224246
0.090213
2.839170
N -1.746792
0.960830
-0.858101
N
1.564942
0.910242
O -3.524193 -0.580855
1.978695
O -2.449788 -2.053063
0.118322
O -4.829343 -1.392165
-0.174198
3.911232
23
O -0.936434
P
0.378805
0.215031
-3.469779 -0.855130
0.512977
C
5.437819
1.664114
0.936370
H
5.700538
1.808621
1.987856
C
6.150051
0.488371
0.351590
C
6.658842
-0.530012
1.174815
C
6.351259
0.380465
-1.035662
C
7.333624
-1.617963
0.641060
H
6.537961 -0.464125
2.253646
C
7.022331
-0.701120
-1.582083
H
5.985813
1.161651
-1.698094
C
7.528543
-1.727398
-0.752775
H
7.724386 -2.388603
1.298938
H
7.171352 -0.759627
-2.656295
H
5.663753
2.585625
0.394848
N
8.160085 -2.817883
-1.291858
H
8.484447 -2.769506
-2.245284
H
8.703135 -3.413521
-0.686102
24
2h
ZPE = 0.683646
E = -1861.889061
H = -1861.888117
G = -1861.008996
C
3.380643
-0.864488
0.259604
H
4.138298 -1.161735
-0.469738
C
3.788242
-1.590966
1.617255
C
3.716458
-3.117837
1.413204
H
3.978936 -3.618550
2.350223
H
4.422192 -3.462235
0.651601
H
2.711560 -3.440281
1.130344
C
2.891605
-1.226713
2.815580
H
1.863192 -1.575666
2.678737
H
2.887517 -0.153079
3.008759
H
3.272326 -1.730463
3.709768
C
5.247108
-1.244166
1.991583
H
5.357915 -0.210809
2.324256
25
H
5.934150 -1.405797
1.155990
H
5.563105 -1.891588
2.815277
C
5.914306
2.309318
0.175678
H
5.639987
2.816007
1.105892
H
5.591288
2.924140
-0.671141
C
7.399565
2.017191
0.111419
H
7.714551
1.402680
0.958674
H
7.959155
2.956949
0.141811
H
7.655131
1.494785
-0.814267
C
2.053535
2.637198
-1.130684
H
1.773452
2.925900
-0.114120
H
1.185714
2.174845
-1.617609
C
2.550825
3.827328
-1.932033
H
3.392656
4.311820
-1.430074
H
1.750141
4.566741
-2.040186
H
2.873480
3.520417
-2.930544
C
2.011325
-1.845525
-1.685290
C
3.015740
-3.005608
-1.837131
H
4.056149 -2.692859
-1.730643
H
2.911305 -3.412898
-2.846366
H
2.819174 -3.809892
-1.126821
C
2.299273
-0.783921
-2.760926
H
1.596580
0.049401
-2.698525
H
2.202169 -1.238601
-3.751766
H
3.307435
-2.678069
-0.374926
26
C
0.610358
-2.442567
-1.908560
H
0.346856 -3.129957
-1.098104
H
0.595427 -3.004407
-2.846429
H -0.154594 -1.668391
-1.986152
C
0.100159
-0.464632
0.835399
H
0.349037
-1.392752
1.356107
C
-1.276643 -0.591233
0.219443
C
-1.631669
0.134487
-0.931864
H -0.888200
0.734827
-1.442803
C
-2.914195
0.066951
-1.430355
H -3.221396
0.596185
-2.324584
-3.550952 -1.407848
0.294537
H -4.346606 -2.006940
0.721299
C
-2.280678 -1.367338
0.826980
H -2.066402 -1.957301
1.711783
C
0.044246
0.717891
1.826211
H
1.053285
0.928310
2.184786
H -0.616721
0.490724
2.668605
H -0.323731
1.620074
1.327734
2.057802 -1.325757
-0.262678
N -3.864011 -0.694315
-0.820284
O
3.068474
1.698205
1.531280
O
3.087722
1.631854
-1.071765
O
5.200380
1.038790
0.110978
O
1.090782 -0.222704
-0.162016
C
N
27
P
3.606997
0.996854
0.328451
C
-5.227876 -0.802870
-1.401990
H -5.192801 -0.319845
-2.381951
H -5.430100 -1.862333
-1.576003
C
-6.329612
-0.184424
-0.554908
C
-7.548692 -0.861325
-0.434304
C
-6.185280
1.078687
0.037585
C
-8.621316 -0.287787
0.251970
H -7.680684 -1.840035
-0.885108
C
-7.240856
1.664443
0.734059
H -5.250007
1.623391
-0.042277
C
0.965820
0.819696
H -9.562980 -0.824270
0.329672
H -7.117747
2.645463
1.184092
N -9.585233
1.596678
1.549105
H -9.838211
2.509242
1.146802
H -10.425254
1.006821
1.506059
H -9.373413
1.748269
2.544493
-8.441791
28
-1.5
-1
log(kd /s )
-2.0
-2.5
-3.0
-1
1/T (K )
-3.5
0.00287
0.00294
0.00301
0.00308
0.00315
Figure 1SI. log(kd/s-1) vs 1/T for 2a.
-3.2
-3.2
NO2
+
-3.8
OMe
-4.2
-4.4
-4.4
0.10
OMe
NMe2
+
0.12
0.14
0.16
0.18
0.20
0.22
0.24
0.0
I,4-XC6H4
0.2
0.4
0.6
0.8
(b)
-3.2
NO2
-3.25
NO2
-3.4
CN
H
-3.6
F
'
'
-1
-1
CN
H
F
log(kd/s )
-3.50
1.0
I,X
(a)
log(kd/s )
-
NHMe2,Br
-4.0
-4.2
0.08
F
-3.6
-3.8
-
NHMe2,Br
NMe2
-4.0
H
-1
'
F
-3.6
'
-1
CN
H
log(kd/s )
log(kd/s )
-3.4
NO2
CN
-3.4
-3.75
+
OMe
-
NHMe2,Br
NMe2
+
-3.8
OMe
-
NHMe2,Br
NMe2
-4.0
-4.00
-4.2
-4.25
-4.4
-4.50
-0.90
-0.75
-0.60
-0.45
-0.30
R,X
-0.15
0.00
-0.20
0.15
(c)
-0.15
-0.10
-0.05
R,4-XC6H4
0.00
0.05
(d)
Figure 2SI. Plot log(kd’/s-1) against I,4-XC6H4 (a), against I,X (b), R,4 (c), R,4-XC6H4 (d) for
2a-g. () and () for RR/SS and RS/SR diastereoisomers, respectively. Red symbols are for
outliers.
29
1 P. Brémond, S. R. A. Marque, Chem. Commun., 2011, 47, 4291-4293.
2 P. Brémond, A. Koïta, S. R. A. Marque, V. Pesce, V. Roubaud, D. Siri, Org. Lett., 2012, 14,
358-361.
3 H. Enomoto, Y. Morikawa, Y. Miyake, F. Tsuji, M. Mizuchi, H. Suhara, K. Fujimura, M.
Horiuchi, M. Ban, Biorg. Med. Chem. Letters, 2009, 19, 442-446.
4 Gaussian 09, Revision A.02, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M.
A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H.
Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L.
Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta,
F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R.
Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J.
Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken,
C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R.
Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A.
Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B.
Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian, Inc., Wallingford CT, 2009.
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