LONG-RANGE POLAR AND STERIC EFFECTS
IN PROPIONATE-SG1-TYPE
ALKOXYAMINES (SG1-CHMeCOOX): A MULTIPARAMETER ANALYSIS
Gennady Ananchenko, Emmanuel Beaudoin, Denis Bertin, Didier Gigmes, Pierre Lagarde,
Sylvain R. A. Marque*, Eve Revalor and Paul Tordo
In memoriam of Prof Hanns Fischer, deceased 22 February 2005
UMR 6517 case 542, Université de Provence, Avenue Escadrille Normandie-Niemen, 13397
Marseille Cedex 20 France. FAX: 33-4-91-28-87-58, e-mail: sylvain.marque@up.univ-mrs.fr
Experimental section
2-({tert-Butyl[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]amino}oxy] propanoic acid 2fluoroethyl ester 18. 25 (4.00 g, 10.9 mmol), SOCl2 (2.4 mL, 32.7 mmol), 2-fluoroethanol
(1.7 g, 21.8 mmol), triethylamine (1.5 mL, 10.9 mmol), DMAP (0.3 g, 2.4 mmol). Colourless
viscous oil. Yield: 20 % of both diastereoisomers (61/49). ESI-MS: C18H37NO6PF, MM: 413g
mol-1; pseudo-molecular ion peak, [M+H]+: m/z = 414. RS/SR isomer.
31
P NMR (CDCl3,
121.59 MHz): 24.2. 1H NMR (CDCl3, 300 MHz): 1.13, s, 9H, (H7), 1.18, s, 9H (H5); 1.251.33, m, 6H (H1); 1.51, d, 3H (JH-H = 9.0 Hz, H9); 3.35, d, 1H (JH-P = 27.0 Hz, H3); 3.85-4.81,
m, 9H (H2, H8, H11, H12). 13C NMR (CDCl3, 75.48 MHz ): 16.8, 2C (d, JC-P = 6.0 Hz, C1);
18.4, 1C (s, C9); 28.3, 3C (s, C7); 30.4, 3C (d, JC-P = 6.0 Hz, C5); 35.6, 1C (d, JC-P = 6.0 Hz,
C4); 59.2, 1C (d, JC-F = 7.5 Hz, C12); 61.8, 1C (s, C6); 62.3, 1C (d, J C-P = 6.0 Hz, C2); 63.6,
1C (d, JC-P = 20.4 Hz, C2); 69.5, 1C (d, JC-P = 139.0 Hz, C3); 81.5, 1C (d, JC-F = 170.6 Hz,
C11); 78.0, 1C (s, C8); 172.8, 1C (s, C10). RR/SS isomer.
31
P NMR (CDCl3, 121.59 MHz):
24.6. 1H NMR (CDCl3, 300 MHz): 1.11, s, 9H, (H7); 1.17, s, 9H (H5); 1.25-1.33, m,6H (H1);
1.54d, 3H (JH-H = 9.0 Hz, H9); 3.28, d, 1H (JH-P = 27.0 Hz, H3); 3.88-4.81, m, 9H (H2, H8,
H11, H12). 13C NMR (CDCl3, 75.48 MHz ): 16.5, 2C (d, JC-P = 6.0 Hz, C1); 19.6, 1C (s, C9);
28.2, 3C (s, C7); 29.9, 3C (d, JC-P = 6.0 Hz, C5); 35.9, 1C (d, JC-P = 6.0 Hz, C4); 59.1, 1C (d,
JC-F = 7.5Hz, C12); 62.0, 1C (s, C6); 62.2, 1C (d, JC-P = 6Hz, C2); 63.6, 1C (d, JC-P = 20.4 Hz,
C2); 69.9, 1C (d, JC-P = 139.0 Hz, C3); 81.3, 1C (d, JC-F = 170.6 Hz, C11); 82.8, 1C (s, C8);
174.0, 1C (s, C10).
2-({tert-butyl[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]amino}oxy]
propanoic
acid
2,2,2-trifluoroethyl ester 19. 25 (4.00 g, 10.9 mmol), SOCl2 (2.4 mL, 32.7 mmol), 2,2,2trifluoroethanol (21.8 mmol), triethylamine (1.5 mL, 10.9 mmol), DMAP (0.3 g, 2.4 mmol).
Colourless viscous oil. Yield: 24 % of both diastereoisomers (53/47). ESI-MS:
C18H35NO6PF3, MM: 449 g mol-1; pseudo-molecular ion peak, [M+H]+: m/z = 450. RR/SS
isomer. 31P NMR (CDCl3,121.59 MHz): 24.3. 1H NMR (CDCl3, 300 MHz): 1.11, s, 9H, (H7),
1.17, s, 9H (H5); 1.26-1.34, m, 6H (H1); 1.56, d, 3H (JH-H = 6.0 Hz, H9); 3.29, d, 1H (JH-P =
24.0 Hz, H3); 3.91-4.27, m , 4H (H2); 4.45-4.77, m, 3H ( H8, H11). 13C NMR (CDCl3, 75.48
MHz ): 16.5, 2C (d, JC-P = 8.3 Hz, C1); 18.2, 1C (s, C9); 28.2, 3C (s, C7); 29.9, 3C (d, JC-P =
6.0 Hz, C5); 35.6, 1C (d, JC-P = 4.5 Hz, C4); 59.3, 1C (d, JC-P = 6.8 Hz, C2); 60.1, 1C (q, JC-F
= 30.2 Hz, C11); 61.9, 1C (s, C6); 62.3, 1C (d, JC-P = 7.5 Hz, C2); 69.9, 1C (d, JC-P = 140.4
Hz, C3); 77.7, 1C (s, C8); 171.3, 1C (s, C10). RS/SR isomer. 31P NMR (CDCl3, 121.59 MHz):
24.0. 1H NMR (CDCl3, 300 MHz): 1.14, s, 9H, (H7), 1.18, s, 9H (H5); 1.26-1.34, m, 6H (H1);
1.54, d, 3H (JH-H = 6.0 Hz, H9); 3.37, d, 1H (JH-P = 24.0 Hz, H3); 3.91-4.27, m , 4H (H2);
4.45-4.77, m, 3H ( H8, H11). 13C NMR (CDCl3, 75.48 MHz): 16.8, 2C (d, JC-P = 8.30 Hz, C1);
19.6, 1C (s, C9); 28.3, 3C (s, C7); 30.5, 3C (d, JC-P = 6.0 Hz, C5); 35.9, 1C (d, JC-P = 4.5 Hz,
C4); 59.5, 1C (d, JC-P = 6.8 Hz, C2); 60.6, 1C (q, JC-F =30.2 Hz, C11); 62.2, 1C (d, JC-P = 7.5
Hz, C2); 69.5, 1C (s, C6); 69.9, 1C (d, JC-P = 140.4 Hz, C3); 82.6, 1C (s, C8); 171.5, 1C (s,
C10).
2-({tert-Butyl[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]amino}oxy]
propanoic
2,2-
difluoroethyl ester 20. 25 (4.00 g, 10.9 mmol), SOCl2 (2.4 mL, 32.7 mmol), 2,2difluoroethanol (21.8 mmol), triethylamine (1.5 mL, 10.9 mmol), DMAP (0.3 g, 2.4 mmol).
Colourless viscous oil. Yield: 23 % of both diastereoisomers (61/49). ESI-MS:
C18H36NO6PF2, MM: 431 g mol-1; pseudo-molecular ion peak, [M+H]+: m/z = 432. RR/SS
isomer. 31P NMR (CDCl3,121.59 MHz): 24.4. 1H NMR (CDCl3, 300 MHz): 1.10 s, 9H, (H7),
1.16, s, 9H (H5); 1.22-1.32, m, 6H (H1); 1.54, d, 3H (JH-H = 6.0 Hz, H9); 3.28, d, 1H (JH-P =
24.0 Hz, H3); 3.38-4.39, m, 9H (H2, H11); 4.67, 1H (q, JH-H = 6.0 Hz, H8); 6.17, 1H (tt, JH-H
= 6.0 Hz, JH-F = 6.0 Hz, H12). 13C NMR (CDCl3, 75.48 MHz ): 16.8, 2C (d, JC-P = 6.8 Hz, C1);
18.4, 1C (s, C9); 28.2, 3C (s, C7); 29.8, 3C (d, JC-P = 6.0 Hz, C5); 35.9, 1C (d, JC-P = 5.3 Hz,
C4); 62.1, 1C (s, C6); 62.3, 1C (t, JC-F = 7.5 Hz, C11); 63.1, 2C (d, JC-P = 8.3 Hz, C2); 69.9,
1C (d, JC-P = 140.0 Hz, C3); 78.2, 1C (s, C8); 124.3, 1C (t, JC-F = 241.0 Hz, C12); 172.2, 1C
(s, C10). SR/RS isomer.
31
P NMR (CDCl3,121.59 MHz): 24.2. 1H NMR (CDCl3, 300 MHz):
1.12 s, 9H, (H7), 1.17, s, 9H (H5); 1.22-1.32, m, 6H (H1); 1.50, d, 3H (JH-H = 6.0 Hz, H9);
3.35, d, 1H (JH-P = 24.0 Hz, H3); 3.38-4.39, m, 9H (H2, H11); 4.67, 1H (q, JH-H = 6.0 Hz, H8);
5.87, 1H (tt, JH-H = 6.0 Hz, JH-F = 6.0 Hz, H12). 13C NMR (CDCl3, 75.48 MHz): 16.5, 2C (d,
JC-P = 6.8 Hz, C1); 19.6, 1C (s, C9); 28.4, 3C (s, C7); 30.4, 3C (d, JC-P = 6.0 Hz, C5); 35.6, 1C
(d, JC-P = 5.3 Hz, C4); 59.3, 1C (t, JC-F = 7.5 Hz, C11); 61.9, 1C (s, C6); 62.7, 2C (d, JC-P = 8.3
Hz, C2); 69.5, 1C (d, JC-P = 140.0 Hz, C3); 82.6, 1C (s, C8); 111.3, 1C (t, JC-F = 241.5 Hz,
C12); 173.3, 1C (s, C10).
2-({tert-Butyl[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]amino}oxy] propanoic acid
2,2,2-trichloroethyl ester 21. 25 (4.00 g, 10.9 mmol), SOCl2 (2.4 mL, 32.7 mmol), 2,2,2trichloroethanol (21.8 mmol), triethylamine (1.5 mL, 10.9 mmol), DMAP (0.3 g, 2.4 mmol).
White powder. Yield: 24 % of both diastereoisomers (53/47). For C18H35O6NPCl3: calculated:
43.46% C, 7.04% H, 2.81% N; found: 43.55% C, 7.04% H, 2.62% N. RR/SS isomer.
31
P
NMR (CDCl3,121.59 MHz): 25.0. 1H NMR (CDCl3, 300 MHz): 1.12, s, 9H (H7), 1.17, s, 9H
(H5); 1.24-1.32, m, 6H (H1); 1.58 , d, 3H (JH-H=6.0 Hz, H9); 3.27, d, 1H (JH-P = 24.0 Hz ,
H3); 3.91-4.34, m, 4H (H2); 4.68-4.80, m, 3H (H8, H11).
13
C NMR (CDCl3, 75.48 MHz):
17.1, 2C (d, JC-P = 8.30 Hz, C1); 20.4, 1C (s, C9); 28.9, 3C (s, C7); 30.5, 3C (d, J C-P = 6.0 Hz,
C5); 36.5, 1C (d, JC-P = 4.5Hz , C4); 59.9, 1C (d, JC-P = 7.5 Hz, C2); 62.7, 1C (s, C6); 62.8, 1C
(d, JC-P = 6.8 Hz, C2); 70.5, 1C (d, JC-P = 140.4 Hz, C3); 75.0, 1C (s, C11); 78.3, 1C (s, C8);
95.5, 1C (s, C12); 172.9, 1C (s, C10). RS/SR isomer 31P (CDCl3,121.59 MHz): 24.6. 1H NMR
(CDCl3, 300 MHz): 1.14, s, 9H (H7), 1.18, s, 9H (H5); 1.24-1.32, m, 6H (H1); 1.58 , d, 3H
(JH-H = 6.0 Hz, H9); 3.36, d, 1H (JH-P = 24.0 Hz, H3); 3.91-4.34, m, 4H (H2); 4.68-4.80, m,
3H (H8, H11).
13
C NMR (CDCl3, 75.48 MHz): 17.5, 2C (d, JC-P = 8.3 Hz, C1); 18.9, 1C (s,
C9); 28.9, 3C (s, C7); 31.1, 3C (d, JC-P = 6.0 Hz, C5); 36.1, 1C (d, JC-P = 4.5 Hz, C4); 59.7, 1C
(d, JC-P = 6.8 Hz, C2); 62.5, 1C (s, C6); 62.9, 1C (d, JC-P = 7.5 Hz, C2); 70.1, 1C (d, JC-P =
140.4 Hz, C3); 74.1, 1C (s, C11); 83.6, 1C (s, C8); 96.1, 1C (s, C12); 171.7, 1C (s, C10).
2-({tert-Butyl[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]amino}oxy] propanoic acid
2,2,2-tribromoethyl ester 22. 25 (4.00 g, 10.9 mmol), SOCl2 (2.4 mL, 32.7 mmol), 2,2,2tribromoethanol (21.8 mmol), triethylamine (1.5 mL, 10.9 mmol), DMAP (0.3 g, 2.4 mmol).
White powder. Yield: 20 % of both diastereoisomers (74/26). For C18H35O6NPBr3: calculated:
34.18% C, 5.54% H, 2.21% N; found: 34.33% C, 5.60% H, 2.10% N. RR/SS isomer.
31
P
NMR (CDCl3, 121.59 MHz): 24.5. 1H NMR (CDCl3, 300 MHz): 1.15, s, 9H, (H7), 1.19, s,
9H (H5); 1.26-1.34, m, 6H (H1); 1.68, d, 3H (JH-H = 6.0 Hz, H9); 3.30, d, 1H (JH-P = 24.0 Hz,
H3); 3.91-4.40, m, 9H (H2, H8, H11). 13C NMR (CDCl3, 75.48 MHz): 17.0, 2C (d, JC-P = 7.5
Hz, C1); 19.9, 1C (s, C9); 28.4, 3C (s, C7); 30.0, 3C (d, JC-P = 6.8 Hz, C5); 35. 2, 1C (s, C12);
36.0, 1C (d, JC-P = 4.6 Hz, C4); 59.2, 1C (d, JC-P = 7.5 Hz,C2); 62.0, 1C (s, C6); 62.4, 1C (d,
JC-P = 7.5 Hz, C2); 70.0, 1C (d, JC-P = 140.0 Hz, C3); 76.4, 1C (s, C11); 83.2, 1C (s, C8);
172.2, 1C (s, C10). RS/SR isomer.
31
P NMR (CDCl3, 121.59 MHz): 24.1. 1H NMR (CDCl3,
300 MHz): 1.16, s, 9H, (H7), 1.21, s, 9H (H5); 1.26-1.34, m, 6H (H1); 1.64, d, 3H (JH-H = 6.0
Hz, H9); 3.40, d, 1H (JH-P = 27.0 Hz, H3); 3.91-4.40, m, 9H (H2, H8, H11). 13C NMR (CDCl3,
75.48 MHz ): 16.5, 2C (d, JC-P = 7.5 Hz, C1); 18.4, 1C (s, C9); 28.4, 3C (s, C7); 30.7, 3C (d,
JC-P = 6.0 Hz, C5); 35.6, 1C (d, JC-P = 5.3 Hz, C4); 36.4, 1C (s, C12); 59.4, 1C (d, J C-P = 7.5
Hz, C2); 62.3, 1C (d, JC-P = 7.5 Hz, C2); 62.0, 1C (s, C6); 69. 6, 1C (d, JC-P = 140.0 Hz, C3);
76.4, 1C (s, C11); 77.8, 1C (s, C8); 170.9, 1C (s, C10).
Results
Table 1SI. Ea, kd at 120 °C, Electrical (Polar Inductive/Field) Hammett Constantsa I,X and
I,CHMeCOOX, and Steric Charton Constants X and CHMeCOOX.
Eab
X
kd (10-4 s-1)c
I,Xd
Ese
Xf
I,MeCHCOOXg MeCHCOOXh
RR/SS
RS/SR
RR/SS
RS/SR





1
135.4
132.0
2.4
6.8
0.00i
-4.72
2.38
0.09
0.82
2
134.7
130.7
3.0
10.0
-0.01
-2.46
1.24
0.09
0.93
3
132.5
128.8
5.7
18.0
0.01
-1.08
0.76
0.10
0.97
4
132.2
129.1
6.2
16.2
-0.04
-0.84
0.68
0.08
0.98
5
132.0
128.6
6.7
19.0
-0.01
-0.70
0.68
0.09
0.98
6
131.8
127.6
7.1
25.6
-0.01
-0.38
0.56
0.09
0.99
7
131.4
127.6
8.1
25.6
0.03
-0.69
0.70
0.10
0.98
8
131.3
127.8
8.2
24.3
-0.01
-0.67
0.68
0.09
0.98
9
130.8
127.2
10.0
30.0
-0.01
0.00
0.52
0.09
1.00
10
130.9
127.2
9.5
30.0
0.09j
-1.80c
1.36k
0.12
0.92
11
130.1
127.1
12.2
30.6
0.10
-1.80c
1.36k
0.12
0.92
12
128.6
126.8
19.4
33.6
0.11j
-1.80c
1.36k
0.12
0.92
13
129.1
126.1
16.6
41.6
0.12
-1.80c
1.36k
0.12
0.92
14
129.2
126.4
16.1
38.0
0.13
-1.80c
1.36k
0.13
0.92
15
127.5
125.5
27.1
50.0
0.19j
-1.80c
1.36k
0.14
0.92
16
126.8
125.3
33.6
53.2
0.21j
-1.80c
1.36k
0.15
0.92
17
126.4
125.1
38.0
56.4
0.23
-1.80c
1.36k
0.15
0.92
18
130.7
127.6
10.2
28.8
0.08l
-0.73m
0.85k
0.11
0.96
19
128.1
125.3
22.6
53.2
0.16t
-1.72u
1.33k
0.14
0.92
20
128.9
126.7
17.7
34.6
0.12r
-1.20s
1.08k
0.12
O.94
21
129.1
126.4
16.6
38.0
0.14p
-2.31q
1.61k
0.13
0.89
22
130.0
127.3
12.6
28.8
0.14n
-2.55o
1.72k
0.13
0.88
a
See references 1.
respectively.
c
b
Given in references 2 and 3for alkoxyamines 1 – 9 and 10 – 17,
See text.
d
Given in reference 4 unless otherwise mentioned.
e
Given in
reference 5 unless otherwise mentioned. f Given in reference 6 unless otherwise mentioned.
Given by eq. 9.
h
Given by eq. 8.
i
g
Estimated by I,CR1R2R3 = 0.248×I,Ri + 0.00398, see
reference 7. j Given in reference 3. k Given by eq. 6. l Given by eq. 4 in the text, I,CH2F = 0.21
estimated with eq. 4 and I,F = 0.54 given in reference 4.
m
Given by eq. 5 in the text, with
Es(H) = 0.32, Es,CH2F = -0.55 given in reference 5. n Given by eq. 4 in the text, I,CBr3 = 0.35
estimated with Eq. T14-5 given in reference 7 and with I,Br = 0.47 given in reference 4.
o
Given by eq. 5 in the text, with Es(H) = 0.32, Es(CBr3) = -3.35 given in reference 5. p Given
by eq. 4, I,CCl3 = 0.36 given in reference 4.
Es(CCl3) = -2.98 given in reference 5.
r
q
Given by eq. 5 in the text, Es(H) = 0.32,
Given by eq. 4 in the text, I,CHF2 = 0.32 given in
reference 4. s Given by eq. 5, Es(H) = 0.32, Es(CHF2) = -2.98 given in reference 5. t Given by
eq. 4 in the text, I,CF3 = 0.40 given in reference 4. u Given by eq. 5 in the text, Es(H) = 0.32,
Es(CF3) = -2.08 given in reference 5.
Table 2SI. Weight (in %)a of the Different Effects Involved in the C-ON Bond Homolysis in
SG1-Based Alkoxyamines
a
Eqsb
Ic
Esc
c
RSd
I’d
'd
22a
61
39
-
-
-
-
23a
70
30
-
-
-
-
25a
63
-
37
-
-
-
26a
70
-
30
-
-
-
22b
54
46
-
-
-
23b
62
38
-
-
-
25b
57
-
43
-
-
-
26b
65
-
35
-
-
-
7
-
-
-
34
35
31
27
10
-
7
28
25
30
28
-
-
-
33
35
32
The weighting equations are given in reference 8. b a is for RR/SS isomer and b is for SR/RS
isomer. c Polar (I) and steric (Es and ) constants applied to the series 1 – 22. d Stabilizing
(RS), polar (I’) and Steric (’) constants applied to the whole set of data (the series given in
reference 9 and the series 1 – 22).
-2.1
20
21
-1
log(kd /s )
-2.4
8
5
-2.7
4
-3.0
5
4
-3.3
1
-0.6
7
21 19
22
9
8
19
18
22
3
2
1
-3.6
6 9
20
18
7
6
3
2
-0.4
-0.2
0.0
II+Es
0.2
0.4
Figure 1SI. Plot of log(kd/s-1) vs eq. 22a (square) and 22b (circle) at 120 °C, (,) RR/SS
isomers, (,) RS/SR isomers, for alkoxyamines 1 – 9 (filled symbols) and 18 – 22 (open
symbols).
Figure 2SI
-2.0
-2.5
-1
log(kd /s )
-3.0
-3.5
-4.0
-4.5
9.5
10.0
10.5
11.0
11.5
12.0
15.38 RS+18.83 'I+6.79 '
-2
-1
log(kd /s )
0
-4
-6
-8
6
8
10
12
15.38 RS+18.83 'I+6.79 '
Figure 2SI. Plot of log(kd/s-1) vs eq. 28. () for data given in reference 10, () RR/SS
isomers and () RS/SR isomers for alkoxyamines 1 – 22.
References
1. Charton M. J. Phys. Org. Chem. 1999; 12: 275-282.
2. Bertin D, Gigmes D, Maurin R, Tordo P J. Polym. Sci.: Part A: Polym.Chem. 2004; 42:
3504-3515.
3. Bertin D, Gigmes D, Marque SRA, Milardo S, Peri J, Tordo P Coll. Czec. Chem. Commun.
2004; 69: 2223-2238.
4. Charton M. Progr. Phys. Org. Chem. 1981; 13: 119-251.
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