www.bu.edu/qale
Property: log (Anti/Syn) for the products of the following reaction
OH
SiMe3
+ Me3NO
OsO4
SiMe3
HO
OSIZ3
OSIZ3
Reference: B. Lorsbach, A. Prock and W. P. Giering, unpublished results
Related Links:
Property: log (Anti/Syn) for the products of the following reaction: (Analysis)
OH
SiZ3
+ Me3NO
OsO4
OAc
SiZ3
HO
OAc
Summary:
log (A/S) = (25±6) - (0.5±0.3)χ d - (0.16±0.03)θ + (1.0±0.9)Ear
n=9
s = 0.3013
%(χ d+ Ear) = 61
r 2 = 0.944
%θ = 39
General Comments:
Data:
-OSiZ 3
SiMe3
SiMe2Ph
SiEt3
SiMe2Cy
PBu3
SiMePh2
SiMe2(t-Bu)
Si(i-Bu)3
Si(i-Pr)Me2
SiPh3
log (A/S)
*
1.799
0.973
1.301
1.100
0.000
0.079
-0.301
0.903
-1.480
Graphical Analysis:
d
8.55
10.5
6.30
6.20
5.25
12.6
5.70
5.70
6.85
13.25
118
122
132
135
136
136
139
143
132
145
Ear
0.0
1.0
0.0
0.0
0.0
2.2
0.0
0.0
0.0
2.7
4
log (A/S)
3
2
PPh M e
i
3-i
1
0
-1
-2
0
1
2
3
4
i
Interpretation of Graphs:
• Plot of data versus d for Si(p-XC6H4)3(Graph A):
• Slope of the SiR3 line (Graph A):
• The point of intersection of the 2 lines in graph A
• The plot of log (A/S) versus 'i' for SiPhiMe3-i (Graph B): The three points define a
good line, the extrapolation of which to i = zero, gives a value of A/S for SiZ3 =
SiMe3 of approximately 2500.
• Outliers:
• Steric threshold:
Statistical Analysis:
We began the analysis using all the data and a three parameter fit. The resulting regression
equation is
log (A/S) = 25.4 - 0.465χ d - 0.161θ + 1.01E ar
Predictor
Constant
χd
θ
Ear
πp
s = 0.3013
Coef
25.430
-0.4646
-0.16135
1.0109
r 2 = 0.944
%(χ d+ Ear) = 61
Stdev
6.405
0.3092
0.03460
0.9350
r2 (adj) = 0.91
%θ = 39
t-ratio
3.97
-1.50
-4.66
1.08
p
0.011
0.193
0.006
0.329
A plot of calculated versus experimental data suggests that the point for PMe2Cy might be
an outlier. Accordingly, we dropped this point from the analysis. The resulting regression
equation is
log(A/S) = 26.4 - 0.516χ d - 0.167θ + 1.21E ar
Predictor
Constant
χd
θ
Ear
πp
s = 0.1682
Coef
26.425
-0.5163
-0.16712
1.2124
r 2 = 0.985
Stdev
3.587
0.1732
0.01938
0.5252
t-ratio
7.37
-2.98
-8.62
2.31
p
0.002
0.041
0.001
0.082
r2 (adj) = 0.973
We note that the coefficients of this analysis are very close to the coefficients obtained when
all the data are used even though the r2 value increased significantly. In particular, the
coefficient of θ is virtually unchanged. We used the first analysis to generate the steric profile
shown below and report it in the 'summary section' at the top of this page.
Stereoelectronic Profiles:
-18
-19
log (A/S)
-20
-21
-22
-23
-24
-25
110
120
130
140
150
Discussion:
There has been a lively debate over the nature of the transition state for the osmylation of
1
alkenes. Houk suggested that the transition state is stabilized by the 'inside alkoxy effect'.
Based on this model, we would expect that the anti isomer produced by osmylation of
CH2=CHCH(OAc)SiZ3 would be formed via transition state A in Scheme 1, shown below.
The syn isomer would be formed from transition state C, which lacks the stabilizing 'inside
alkoxy effect'. Increasing the size of SiZ3 would have little effect on the anti/syn ratio since
the silyl group is directed away from the site of reaction in both transition states.
2
In contrast, Vedejs suggested that in the most stable transition state, the small hydrogen
would be directed toward the region of greatest congestion. Thus, the anti isomer would be
preferentially formed via transition state B, shown below. The syn isomer would be formed
via transition state D. The Vedejs model suggests that transition state B should be less
congested than transition state D since in D the silyl group is located below the vinyl group
and closest to the reaction site. Thus, the Vedejs model suggests a small steric effect that
would favor the formation of the anti isomer as the size of the silyl group increases.
The QALE analysis of the osmylation of CH2=CHCH(OAc)SiZ3 reveals a small steric effect
that favors the formation of the syn isomer. This would appear to support the Houk model but
the effect is small and, in our opinion, not definitive.
Scheme 1
Houk Model
Vedejs Model
O
O
O
O
Os
Os
O
O
OH
H
AcO
H
O
O
H
SiMe3
H
HO
H
SiZ3
AcO
OAc
A
B
anti
Os
OH
O
O
H
AcO
Os
SiMe3
C
O
HO
H
SiZ3
O
H
H
H
O
O
O
O
AcO
H
SiZ3
H
AcO
SiZ3
syn
D
In the system analyzed on this web page, we kept the silyl group, SiMe3, constant; in place of
the acetoxy group we used the siloxy group and varied its stereoelectronic properties. The
Houk model (Scheme 2) predicts that transtion state E should lead to the anti isomer. Steric
factors should favor the syn transtion state G as the size of the siloxy group increases. Since
the siloxy group is located in the region of reaction in transition state E, we would expect a
large steric effect that would favor the formation of the syn isomer as the size of siloxy group
increases.
In the Vedejs model, the anti isomer would be formed via transition state F when the siloxy
group is small. As the size of the siloxy group increases we would expected that transition
state H would become more favored. Since the siloxy group in transition state H is located on
the face opposite to the incoming OsO4, we would expect the steric effect to be small and
favor the syn isomer as the size of the siloxy groups increases.
Scheme 2
Houk Model
Vedejs Model
O
O
O
O
Os
O
Os
O
OH
H
R3SiO
H
H
O
H
SiMe3
HO
H
SiMe3
H
SiMe3
R3SiO
OSiZ3
E
F
anti
O
O
O
OH
O
O
O
Os
R3SiO
O
Z3SiO
Os
SiMe3
O
O
H
H
HO
H
H
H
SiMe3
H
Z3SiO
SiMe3
syn
G
H
The results of our experiments with CH2=CHCH(OSiZ3)(SiMe3) show a very large steric
effect that favors the syn isomer as the size of the siloxy group increases. This is shown
below where we have placed the two steric profiles on the same graph. (In order to plot the
steric profiles on the same scale, we subtracted 24 from each of the data for the steric profile
for the osmylation of CH2=CHCH(OAc)(SiZ3).)
-18
-20
log (A/S)
-22
-24
-26
-28
-30
110
C H =CHCH(OAc)SiZ
2
3
C H =CHCH(OSiZ )SiMe
2
3
3
120
130
140
150
This large steric effect clearly supports the Houk model.
References
1) a) Houk, K. N.; Moses, S. R.; Wu, Y. D.: Rondan, N. G.; Jager, V.; Schohe, R.; Fronczek,
F. J. Am. Chem. Soc., 1984, 106, 3880. b) Houk, K. N.; Duh, H. Y.; Wu, Y. D.; Moses, S. R.
J. Am. Chem. Soc. 1986, 108, 2754.
2 a) Vedejs, E.; McClure, C. K. J. Am. Chem. Soc. 1986, 108, 1094. b) Vedejs, E.; Dent, W.
H., III J. Am. Chem. Soc. 1989, 111, 6861.