Linear free-energy relationship and rate study on a silylation-based kinetic resolution: Mechanistic insights

Article abstract of DOI:10.1021/jo402569h

The substituent effect of different p-substituted triphenylsilyl chlorides on silylation-based kinetic resolutions was explored. Electron-donating groups slow down the reaction rate and improve the selectivity, while electron-withdrawing groups increase the reaction rate and decrease the selectivity. Linear free-energy relationships were found correlating both selectivity factors and initial rates to the σ_para Hammett parameters. A weak correlation of selectivity factors to Charton values was also observed when just alkyl substituents were employed but was nonexistent when substituents with more electronic effects were incorporated. The rate data suggest that a significant redistribution of charge occurs in the transition state, with an overall decrease in positive charge. The linear free-energy relationship derived from selectivity factors is best understood by the Hammond postulate. Early and late transition states describe the amount of substrate participation in the transition state and therefore the difference in energy between the diastereomeric transition states of the two enantiomers. This work highlights our efforts toward understanding the mechanism and origin of selectivity in our silylation-based kinetic resolution.

Full text of DOI:10.1021/jo402569h

Article
pubs.acs.org/joc
Linear Free-Energy Relationship and Rate Study on a Silylation-Based
Kinetic Resolution: Mechanistic Insights
Ravish K. Akhani, Maggie I. Moore, Julia G. Pribyl, and Sheryl L. Wiskur*
University of South Carolina, Columbia, South Carolina 29208, United States
S
* Supporting Information
ABSTRACT: The substituent effect of different p-substituted triphenylsilyl chlorides on silylation-based kinetic resolutions was
explored. Electron-donating groups slow down the reaction rate and improve the selectivity, while electron-withdrawing groups
increase the reaction rate and decrease the selectivity. Linear free-energy relationships were found correlating both selectivity
factors and initial rates to the σpara Hammett parameters. A weak correlation of selectivity factors to Charton values was also
observed when just alkyl substituents were employed but was nonexistent when substituents with more electronic effects were
incorporated. The rate data suggest that a significant redistribution of charge occurs in the transition state, with an overall
decrease in positive charge. The linear free-energy relationship derived from selectivity factors is best understood by the
Hammond postulate. Early and late transition states describe the amount of substrate participation in the transition state and
therefore the difference in energy between the diastereomeric transition states of the two enantiomers. This work highlights our
efforts toward understanding the mechanism and origin of selectivity in our silylation-based kinetic resolution.
Scheme 1. Previously Reported Kinetic Resolution of
Monofunctional Secondary Alcohols9
INTRODUCTION
■
Enantioselective silylation is becoming an alternative approach
to acylation in order to obtain enantiopure alcohols via kinetic
resolutions and desymmetrization reactions.1−14 Since silyl
groups are one of the most common protecting groups in
organic chemistry, it makes sense to employ them as a means of
separating enantiomers in kinetic resolutions.15,16 The advan-
tages of silyl groups include tunable reactivity, orthogonality to
other protecting groups, and tolerance of many other functional
groups.17 In order to efficiently improve upon the selectivity in
these reactions, and given that there are small energy
differences between selective and unselective kinetic reso-
lutions, a detailed understanding of the mechanism is crucial.
While the mechanism of acylation reactions in relationship to
kinetic resolutions has been highly explored,18−21 there has
been little work accomplished regarding the mechanism of
silylation-based kinetic resolutions.13 In 2011, we published a
report on the silylation-based kinetic resolution of monofunc-
tional secondary alcohols9 that employed the small molecule
nucleophilic catalyst (−)-tetramisole (1)22 and triphenylsilyl
chloride (2a) to silylate one enantiomer over another (Scheme
1) with selectivity factors23,24 up to 25. This report describes
our efforts toward investigating the mechanism of this reaction
by determining how the steric and electronic effects around the
triphenylsilyl chloride affect the reaction in terms of selectivity
as well as reactivity. This will help us to start answering several
questions about charge development in the transition state, the
origin of enantioselectivity, and whether steric or electronic
effects are more important for controlling selectivity.
Previously, we have shown that the selectivity of our kinetic
resolution was dependent on the structure of the silyl chloride.
Specifically, it was determined that three phenyl groups were
strategic in obtaining selectivity. For example, when diphenyl-
methyl and phenyldimethylsilyl chlorides were employed, the
selectivity dramatically decreased as compared to triphenylsilyl
chloride (Scheme 2). The same decrease in selectivity was
obtained when all of the phenyl groups were replaced with alkyl
Received: November 20, 2013
Published: February 21, 2014
© 2014 American Chemical Society
2384
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
a
A rate study of the substituted silyl chlorides was done to
explore the charge developing in the transition state and
provide information on the mechanism of the reaction. Since
kinetic resolutions consist of two substrates competitively
reacting (the two enantiomers), the rate needed to be measured
on one enantiomer at a time. In situ IR was employed to
measure the rate of silylation on the fast-reacting (R)
enantiomer of tetralol 5, employing silyl groups substituted
with hydrogen, halides, methoxy, and alkyl groups (2a−d,f−j)
(eq 1). The reaction conditions were nearly identical to the
Scheme 2. Previously Reported Importance of
Triphenylsilyl Chloride9
conditions in Scheme 1, except for the use of Hunig’s base due
̈
to the lack of availability of the previously employed tertiary
amine, diisopropyl-3-pentyl amine. The initial rate, up to 10%
conversion (8 mmol), was observed in all cases, and the results
are shown in Table 1. Silyl groups substituted with electron-
a
b
See ref 25. Reaction was run with 0.6 equiv of Ph3Si−Cl, 0.6 equiv
of iPr2EtN, and 25 mol % of 1.
groups (Scheme 2). This same effect on selectivity was seen
with a second substrate class, α-hydroxylactones.14 Since the
triphenylsilyl chloride is strategically involved in the enantio-
discriminating step, it can be used as a valuable tool for
exploring the mechanism. We therefore examined the steric and
electronic effects on the silyl chloride to understand more about
the reactivity of the silyl chloride and its role in enantioselective
discrimination through the use of a linear free-energy
relationship (LFER). Ultimately, the knowledge gained from
this study will be used to improve future resolutions and
expand our substrate scope.
Table 1. Rate Study Employing the Fast-Reacting
Enantiomer (R) Using Different para-Substituted
a
Triphenylsilyl Chlorides
a
b
entry
Y
rate of (R)-5 (mmol/min)
RESULTS AND DISCUSSION
1
2
3
4
5
6
7
8
9
H
Br
12
66
■
Linear free-energy relationship analysis is a powerful tool for
investigating reaction mechanisms.26 Recently, increased
interests in employing this technique to evaluate asymmetric
reactions have been reported.27−39 We wanted to use this tool
to investigate the steric and electronic effects on the rate and
selectivity of our silylation-based kinetic resolution in Scheme
1. For this analysis, a series of para-substituted triphenylsilyl
chlorides (2b−l) (Scheme 3) were synthesized to employ in
the kinetic resolution shown in Scheme 1. The substituents
include halides (2b−d), trifluoromethyl (2e), methoxy (2f),
various alkyl groups (2g−k), and phenyl (2l). The synthesis of
the silyl chlorides was accomplished by a three-step process
starting with a lithium−halogen exchange40 or Grignard
formation41 with para-substituted phenyl bromides or iodides
(3b−l). The resultant organometallic compound was reacted
with trichlorosilane to make the triaryl-substituted silanes (4b−
l). The silanes were then converted into the silyl chlorides
(2b−l) by a radical chlorination with sulfuryl chloride.42,43 The
silanes and silyl chlorides were prepared in moderate to good
yields (see Experimental Section).
Cl
68
F
32
OMe
Me
Et
0.09
0.72
0.36
1.0
iPr
tBu
0.29
a
Reactions were carried out at a substrate concentration of 0.08 M on
a 0.3 mmol scale. Each entry is an average of two runs. Rate was
obtained via in situ IR measurements. H NMR conversion was used
to monitor conversion of alcohol to silylated product.
b
1
withdrawing groups (entries 2−4) were up to 5 times faster
than triphenylsilyl chloride (entry 1), and electron-donating
groups (entries 5−9) significantly decreased the rate as much as
2 orders of magnitude versus 2a. The increase in rate when the
silyl chloride is substituted with electron-withdrawing groups is
logical since those substituents would remove electron density
from the silicon, making it more reactive. The same argument
Scheme 3. Synthesis of p-Substituted Triphenylsilyl Chlorides
a
Temperatures of 0 °C to rt were used for 3e, −40 °C for 3h−k, and −78 °C for 3l. See Experimental Section for exact procedures and yields.
2385
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
44
Figure 1. Hammett plot employing the parameter σpara versus the log of rates for the kinetic resolution of the fast-reacting enantiomer (R) of
alcohol 5 (average of two runs).
Scheme 4. Proposed Mechanism of the Silylation Reaction
applies to electron-donating groups increasing electron density
on the silicon, slowing the silylation.
indicates that the substituents in the para position can
contribute to the reactivity of the silicon through some degree
of resonance. The degree of inductive versus resonance
contribution was determined using the Swain−Lupton dual
parameter approach (eq 2).50 The method separates the
Hammett parameter into two parameters, induction/field
effects (F) and resonance (R), with sensitivity factors of r
and f, respectively. Employing F and R parameters recalculated
by Hansch,51 we fit the rate data from Table 1 with a least-
squares regression analysis to solve for the two sensitivity
constants. The similarity of f and r (f = 5.4, r = 5.9) indicates
that induction and resonance contribute equally to the rate of
the reaction. Figure 2 shows the good correlation between
experimentally determined log of rate ratios versus those
predicted by eq 2.
A Hammett plot was generated from the log of the (R)-5
rates in Table 1 versus σpara substituent constants44 (Figure 1),
which shows a linear relationship with a slope or sensitivity
constant of ρ = 5.8 (R2 = 0.94). The fact that a correlation
exists signifies that the mechanism does not change upon
altering the silyl chloride. The considerable magnitude of the
slope (ρ) indicates that the silylation reaction is very sensitive
to electron-withdrawing and -donating groups on the silyl
chloride, signifying a significant redistribution of charges in the
transition state. Finally, the positive slope is suggestive of a
decrease in positive charge in the transition state.26 This
decrease in positive charge and significant redistribution of
charge is consistent with the silylation mechanism proposed by
Chojnowski,45 Bassindale,46,47 and Frye,48 while the mecha-
nisms proposed by Corriu49 and Hoveyda and Snapper13
cannot be ruled out entirely. The mechanism is essentially two
SN2 reactions (Scheme 4), where the first SN2 reaction involves
the nucleophilic catalyst (1 in our system) attacking the silyl
chloride, displacing the chloride to form the reactive tetravalent
intermediate A. An alcohol then does a backside attack on this
intermediate to form the silylated alcohol, regenerating the
nucleophilic catalyst. The proposed transition state for this last
step is similar to the classical SN2 transition state with the
nucleophilic catalyst (1) departing as the alcohol is attacking.
This involves a redistribution of the positive charge from a full
positive charge on intermediate A to partial positive charges on
the incoming alcohol oxygen and the departing catalyst 1,
displaying an overall decrease in positive charge in the
transition state. This proposed transition state can be employed
in an effort to understand the origin of enantioselectivity.
Since the σpara parameter incorporates both inductive and
resonance contributions, the linear correlation of the rate data
⎛
⎞
kx
log
= fF + rR
⎜
⎟
⎠
k
⎝
(2)
H
As was stated earlier, LFERs have been employed to study
asymmetric reactions and provide information about the source
of enantioselectivity. While these LFER studies mainly employ
enantiomeric ratios as a way of measuring the change in the free
energy of activation, traditionally, a ratio of pure rates is
employed in the analysis as seen in the study above. Recently, it
was suggested that selectivity factors from kinetic resolutions
could be employed in a LFER analysis52 since selectivity factors
are a ratio of rates.24
Two alcohols were chosen for the kinetic resolution reactions
(eq 3) employing the p-substituted silyl chlorides: tetralol (5)
and 4-chromanol (7). These alcohols were chosen since they
displayed moderate selectivity under the reaction conditions,
allowing us to see subtle differences in selectivity as the
substituents are altered on the silyl chlorides. These subtle
2386
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
selectivity factors of 13 and 21 for 5 and 7, respectively, versus
the new selectivity factors of 11 and 15. Employing the silyl
chlorides with substituents in the para position proved
satisfactory at affecting the selectivity of the kinetic resolution
reactions of 5 and 7. The use of halide-substituted silyl
chlorides (2b−d) reduced the selectivity factors (entries 2−4
and 14−16) for both alcohols. The selectivity of the kinetic
resolution employing para-bromide-substituted silyl chloride
(2b) was nearly half compared with the selectivity of employing
2a. Both electron-withdrawing and electron-donating groups on
the silyl chloride, trifluoromethyl (2e) (entries 5 and 17) and
methoxy (2f) (entries 6 and 18), respectively, caused a
reduction in selectivity when compared to 2a. Silyl chlorides
substituted with alkyl groups (2g−k) resulted in an increase in
selectivity, with the bulkier groups resulting in the best
selectivity (entries 7−11 and 19−23).
Hammett plots were generated (Figure 3) by plotting σpara
parameters versus the log of the selectivity factors from Table 2
for alcohols 5 and 7. This explores the electronic contribution
of silyl chlorides 2a−l and how electronic effects affect
selectivity. A correlation was observed with the silylation-
based kinetic resolution showing that it is sensitive to the
electronic effects of the triphenylsilyl chlorides. For both
alcohols 5 and 7, the same trend was observed, a negative slope
in both, suggesting a decrease in selectivity factors when
electron-withdrawing groups are employed. The selectivity
Figure 2. Comparison of the experimental log(kx/kH) using the rate
data from Table 1 versus the predicted log(kx/kH) calculated from eq
2.
changes would be missed if highly selective substrates were
employed. The same reaction conditions as the rate study were
employed, and the selectivity factors for the reactions are
shown in Table 2. Entries 1 and 13 show the small detrimental
effect of switching the base from diisopropyl-3-pentyl amine to
Hunig’s base when we compare the originally published
̈
a
Table 2. Kinetic Resolution Using Different para-Substituted Triphenylsilyl Chlorides
b
b
entry
alcohol
Y
t (h)
conv (%)
er of recovered alcohol
s
1
2
5
5
5
5
5
5
5
5
5
5
5
5
7
7
7
7
7
7
7
7
7
7
7
7
H
Br
24
24
24
24
24
48
48
48
48
69
72
72
24
24
24
24
24
48
48
48
48
69
72
72
50
46
34
52
35
43
49
36
51
42
34
22
49
41
50
48
21
46
56
45
48
47
44
17
85:15
75:25
66:34
85:15
65:35
77:23
86:14
72:28
88:12
79:21
71:29
62:38
85:15
73:27
86:14
85:15
60:40
81:19
94:6
11
6
3
Cl
7
4
F
9
5
CF3
OMe
Me
Et
5
6
10
14
13
14
16
15
11
15
8
7
8
9
iPr
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
tBu
C6H11
Ph
H
Br
Cl
11
13
7
F
CF3
OMe
Me
Et
11
14
17
20
28
21
13
83:17
87:13
88:12
83:17
59:41
iPr
tBu
C6H11
Ph
a
b
Reactions were carried out at a substrate concentration of 0.16 M on a 0.22 mmol scale. See ref 25.
2387
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
hydrogen substituent. Therefore, the transition state would
resemble the silyl chloride/catalyst intermediate with very little
involvement of the attacking chiral alcohol (Figure 4A). With
little alcohol participation in the transition state, the difference
between the diastereomeric transition state energies for both
enantiomers is small; therefore, the chiral catalyst intermediate
cannot easily distinguish between the enantiomers, leading to
low selectivity. When electron-donating groups are employed,
the transition state shifts to contain more product-like character
with more participation of the attacking alcohol (Figure 4B).
Therefore, there is a larger energy difference between the
transition states of the two enantiomers, leading to higher
selectivity.
Many asymmetric reactions have exhibited a relationship
between enantioselectivity and steric effects on the catalyst or
reactant.52,53 The sensitivity of the reaction presented herein to
steric effects was investigated to establish if a correlation
between steric effects and selectivity exists since selectivity
factors for the kinetic resolution of 5 and 7 in eq 3 do increase
as the alkyl substituents on 2 increase in size (entries 7−11 and
19−23). For example, by substituting a t-butyl group for a
hydrogen, the selectivity factor increases from 15 to 28 when
employing 7. The log of the selectivity factors for all the silyl
chlorides (2a−l) and the two alcohols were plotted against the
Charton (υ) parameters (Figure 5A,B). Charton values54−57 are
steric parameters that are based on the van der Waals radius of
the substituent and have been employed to show correlations
between enantioselectivity and steric effects in a variety of
asymmetric systems.52,58−60 When all of the substituents are
plotted on the same graph, there is no observable correlation to
the size of the substituent.
When the substituents that have a more pronounced
electronic effect are removed, and just alkyl substituents
(methyl, ethyl, isopropyl, t-butyl, and cyclohexyl) are plotted
(Figure 5C), there appears to be a small correlation to steric
effects in the para position of triphenylsilyl chloride (Ψ = 0.13
and 0.23 for 5 and 7, respectively). The small magnitude of the
slope suggests that the correlation is minor, and the lack of a
correlation when all of the substituents are plotted together
(Figure 5A,B) indicate that electronic effects play a more
significant role.
44
Figure 3. Hammett plots employing the parameter σpara versus the
log of the selectivity factors for the kinetic resolution of alcohols (gray
triangle) 5 and ( ) 7 (σpara values not listed in Figure 1; CF3 = 0.54,
■
Ph = −0.01, C6H11 = −0.15).
improved when electron-donating groups were employed but
only up to a point. When the strongest electron-donating group
in the series was used, methoxy, it did not follow the linear
trend and instead decreased in selectivity. The sensitivity for
both substrates was nearly the same with ρ = −0.73 (R2 = 0.95)
and −0.69 (R2 = 0.80) for 5 and 7, respectively, not including
methoxy.
The sensitivity of the reaction to electronic changes on the
silyl chloride can be explained by the Hammond postulate,
proposed by Jacobsen in his own linear free-energy relationship
study.29,30 In our study, when electron-withdrawing groups are
on the silyl chloride (2b−e), the silyl chloride/catalyst
intermediate is more reactive and higher in energy versus a
In order to determine the contribution of steric effects to the
overall selectivity, a dual parameter approach was undertaken
Figure 4. Hammond postulate diagram explaining electronic effect on selectivity factors. (A) Early transition state with electron-withdrawing
substituents on silyl chloride. (B) Late transition state with electron-donating substituents on silyl chloride.
2388
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
■
Figure 5. Charton analysis of alcohols (A) 5 (gray triangle), (B) 7 ( ), and (C) selected alkyl-substituted silyl chlorides (2a−l) in the silylation-
based kinetic resolution.
involving σpara and Charton (υ) parameters. Least-squares
regression analysis was performed on eq 4 using the selectivity
data for 5 (Table 2, entries 1−5 and 7−12) to determine the
sensitivity constants ρ and Ψ for the electronic and steric effect
contributions, respectively. The sensitivity constant related to
electronic effects (ρ) was an order of magnitude larger than the
sensitivity constant for steric effects (Ψ). This indicates that
steric effects do not play a significant role in the selectivity of
the reaction. Figure 6 shows the good correlation between the
experimental log(s) versus that predicted by eq 4.
in Table 3. For three substituted silyl chlorides and 2a, we also
experimentally measured the rate of silylation of (S)-5 to verify
that the calculated rates were correct. The experimental rates
are shown in parentheses and show good correlation to the
calculated rates. Electron-donating groups again slow down the
silylation (entries 5−9), while electron-withdrawing groups
speed up the silylation (entries 2−4) when compared to
hydrogen in the para position (entry 1). The Hammett plot for
the calculated rates is shown in Figure 7, again employing σpara
substituent constants. The calculated rates have a linear
relationship, with a sensitivity constant (ρ) of 6.4, which is
slightly higher than the sensitivity constant of the fast-reacting
enantiomer (ρ = 5.8). This shows that the substituted silyl
chlorides essentially have the same effect on both the fast- and
slow-reacting enantiomers (i.e., same sign of the slope therefore
same transition state), with the sensitivity of the slow-reacting
log(s) = ρσpara + ψυ
(4)
With selectivity factors and the rate of the fast-reacting
enantiomer in hand for alcohol 5, the rate of the slow-reacting
enantiomer ((S)-5) (eq 5) was calculated based on the
selectivity factor definition.24 These calculated rates are shown
2389
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
fast-reacting enantiomer since the selectivity factor is a ratio of
these rates. Therefore, the slow-reacting enantiomer is slightly
more sensitive to changes in electronic effects.
CONCLUSIONS
■
In conclusion, we determined that mainly electronic effects
around the triphenylsilyl chloride affect both the rate and the
selectivity of the silylation-based kinetic resolution presented
herein. Substituting the triphenylsilyl chlorides in the para
position with a variety of electron-withdrawing and -donating
groups allowed us to investigate the mechanism of our
silylation-based kinetic resolution. The rates of the silylation
reaction were measured employing the fast-reacting enantiomer
with different para-substituted triphenylsilyl chlorides and a
linear free-energy relationship was discovered employing σpara
parameters. The sign and magnitude of the slope indicates that
positive charge is decreasing in the transition state, and there is
a significant redistribution of the charge. From these data, we
were able to postulate a pentavalent SN2-like transition state
with the tetramisole catalyst as the leaving group and the
alcohol as the incoming nucleophile. By employing the
substituted triphenylsilyl chlorides in kinetic resolutions,
selectivity factors were obtained that indicate electronic effects
on the silyl group play a more significant role than steric effects
in affecting the selectivity of the reaction. Ultimately, electron-
donating groups result in a late transition state according to the
Hammond postulate, where the incoming alcohol is more
involved in the rate-determining step, and therefore, the
diastereomeric transition states between the two enantiomers
have a larger energy difference as compared to electron-
withdrawing substituted triphenylsilyl chlorides. Ultimately,
with this linear free-energy relationship study, we have been
able to postulate the transition state and obtain some
understanding on the enantioselective step, which can aid in
future substrate expansion. Future studies will include employ-
ing a chiral silyl chloride for further evidence of a double
inversion mechanism and an NMR and kinetic study to get a
complete picture of the overall mechanism.
Figure 6. Comparison of the experimental log(s) using the selectivity
data for 5 from Table 2 versus the predicted log(s) calculated from eq
4.
Table 3. Rate of Slow-Reacting Enantiomer (S)-5 for
Different para-Substituted Triphenylsilyl Chlorides
a
entry
Y
rate of (S)-5 (mmol/min)
1
2
3
4
5
6
7
8
9
H
Br
1.1 (1.2)
11 (9.5)
9.7
Cl
F
3.6
OMe
Me
Et
0.009 (0.02)
0.05
0.03
iPr
tBu
0.07 (0.06)
0.02
a
Calculated rate based on selectivity factor and fast-reacting
EXPERIMENTAL SECTION
■
enantiomer. Rate in parentheses was experimentally measured on a
0.3 mmol scale at 0.08 M. Each data point is a single run.
General Information. All kinetic resolution reactions and the
synthesis of different silanes and silyl chlorides were carried out under
a N2 atmosphere using oven-dried glassware. All solvents including
THF, diethyl ether, and hexanes were dried by passing through a
column of activated alumina before use and stored over molecular
sieves. Pentane and carbon tetrachloride were distilled and stored over
molecular sieves. CCl4 was degassed before chlorination. Sulfuryl
chloride was distilled prior to use. n-BuLi was titrated prior to use. All
other chemicals were purchased from a commercial source and used
without further purification. Molecular sieves were activated for 48 h at
130 °C in an oven. Flash column chromatography was performed with
silica gel (32−63 μm). High-resolution mass spectrometry (HRMS)
was obtained using a magnetic sector mass spectrometer. IR data
(νmax) are reported in cm−1. Rate data were collected using an FTIR
spectrophotometer with a silicon probe. All enantiomeric ratios were
determined by HPLC using the chiral stationary phase Chiralcel OD-
H (4.6 × 250 mm ×5 μm) column and monitored using a photodiode
array detector in comparison with authentic racemic materials. Melting
points (mp) are uncorrected. Optical rotations were obtained using a
polarimeter. Microwave-assisted transformations were carried out
using a chemical synthesis microwave. NMR spectra were obtained at
room temperature using 400 MHz (1H), 101 MHz (13C), 80 MHz
Figure 7. Hammett plot employing the parameter σpara44 versus the log
of the calculated rates for the kinetic resolution of the slow-reacting
enantiomer (S)-5.
enantiomer to the substituents being modestly higher. This
suggests that substituting the silyl chloride with electron-
donating groups improves the selectivity of the reaction by
affecting the rate of the slow-reacting enantiomer more than the
1
(29Si), and 377 MHz (19F). Chemical shifts for H, 13C, 19F, and 29Si
was recorded in part per million with either TMS (0.00 ppm) or
1
CDCl3 (7.26 ppm for H or 77.0 ppm for 13C) as a reference. TMS
2390
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
was used as a reference (0.00 ppm) to obtain 29Si NMR. Data reported
in 1H NMR are as follows: chemical shift, multiplicity (s = singlet, d =
doublet, t = triplet, q = quartet, dd = doublet of doublet, dt =doublet
of triplet, sept = septet, m = multiplet) and coupling constant (Hz).
General Procedure Making a p-Substituted Triphenylsilane.
General Procedure 1 (GP1):40 (Written for a 10 mmol scale with
regards to aryl bromide or iodide.) Important note regarding silane
synthesis: Extreme caution should be undertaken while centrifuging and
washing the lithium salts.61 These salts are highly flammable and any
contact with air or water should be avoided, especially when the para-
substituent is an electron-withdrawing group. In an oven-dried 250 mL
three-neck round-bottom flask, p-substituted bromo/iodobenzene (1
equiv) was dissolved using previously distilled pentane (28 mL) under
nitrogen at room temperature. To the stirred solution was slowly
added n-BuLi (1.025 equiv) at room temperature. After addition of n-
BuLi, the resulting mixture formed a precipitate which was then
allowed to stir for 1−1.5 h. After 1−1.5 h, the white precipitate
containing solution was carefully transferred to a test tube and
centrifuged for 5 min (four test tubes were used). The supernatant was
carefully removed using a syringe (done under N2 atmosphere). The
white precipitate was washed 2−3 times using dry pentane and
transferred to another three-neck round-bottom flask using approx-
imately 22 mL of fresh pentane under nitrogen. A solution of HSiCl3
(0.4 M in pentane, 0.3 equiv) was added dropwise to the three-neck
flask (Caution: exothermic reaction). The reaction mixture was then
allowed to stir for another 2 h. After 2 h, the resulting suspension
(white precipitate) was centrifuged (four test tubes were used). The
supernatants were collected under nitrogen in a separate round-
bottom flask (liquid was collected using a syringe and transferred to
another flask carefully). The remaining solid was washed 2−3 times
with pentane and centrifuged, and the supernatants were combined
with the previously collected supernatants. Finally, the combined
supernatants were quenched by chlorotrimethyl silane, and the
resulting solution was concentrated under vacuum to yield the crude
triphenylsilane product. In most cases, purification of silane was done
by recrystallization using an appropriate solvent.
General Procedure 2 (GP2): (Written for a 10 mmol scale with
regards to aryl bromide or iodide.) In an oven-dried 250 mL three-
neck round-bottom flask, p-substituted bromo/iodobenzene (1 equiv)
was dissolved using previously dried diethyl ether (30 mL) under
nitrogen at room temperature. To the stirred solution was added n-
BuLi (1.025 equiv), and the resulting mixture was allowed to stir for
1−1.5 h at room temperature. The reaction was then cooled to −40
°C using a dry ice−acetonitrile bath. A solution of HSiCl3 (0.4 M in
ether, 0.3 equiv) was added dropwise to the three-neck flask. The
reaction mixture was allowed to stir for another 2 h at −40 °C, then
the reaction was quenched using 10 mL of water at −40 °C and
allowed to warm to room temperature. Extraction was done using
diethyl ether. The organic layer was collected and dried over
anhydrous sodium sulfate. The excess solvent was removed via a
rotary evaporator, and the crude was purified using recrystallization or
a trituration method.
78%): 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.0 Hz, 6 H), 7.39
(d, J = 8.0 Hz, 6 H), 5.39 (s, 1H); 13C NMR (101 MHz, CDCl3, 25
°C) δ 137.1, 131.5, 131.0,125.4.
Tris(4-bromophenyl)chlorosilane (2b).40 Chlorination was done
employing 4b (1.1 g, 2.21 mmol) according to GP3. Silane was
dissolved using 12 mL of degassed carbon tetrachloride followed by
addition of sulfuryl chloride (895 μL, 11 mmol) under nitrogen. The
resulting mixture was allowed to reflux for 10−12 h. The final solid
product was obtained by recrystallization using pentane at −40 °C
(430 mg, yield = 37%): 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.2
Hz, 6H), 7.46 (d, J = 8.2 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ
136.5, 131.6, 130.6, 126.4.
Tris(4-chlorophenyl)silane (4c). The product was synthesized
employing 1-chloro-4-iodobenzene (98%) (2.43 g, 10 mmol)
according to GP1. The final product was obtained by recrystallization
from pentane at −40 °C to yield colorless crystals (680 mg, yield =
1
62%): mp = 74−76 °C; H NMR (400 MHz, CDCl3) δ 7.46 (d, J =
8.3 Hz, 6H), 7.38 (d, J = 8.3 Hz, 6H), 5.43 (s, 1H); 13C NMR (101
MHz, CDCl3) δ 136.9, 136.8, 130.6, 128.6; 29Si NMR (80 MHz,
CDCl3) δ −18.6; HRMS (EI) (M+) calcd for (C18H13Cl3Si+)
361.9846, observed 361.9858; IR (neat, cm−1) 3042, 2142, 1578,
1481, 1380, 1080, 1013, 821, 798, 778, 740, 733, 698.
Chlorotris(4-chlorophenyl)silane (2c). The product was obtained
using 4c (650 mg, 1.78 mmol) according to GP3. The silane was
dissolved in 10 mL of degassed carbon tetrachloride under N2. Excess
sulfuryl chloride (750 μL, 9.26 mmol) was added over the course of
the reaction. The reaction took 28 h to go to completion, monitored
by 1H NMR. The crude was triturated with pentane at −78 °C using a
dry ice/acetone bath to yield a colorless solid (295 mg, yield = 40%):
mp = 58−60 °C; 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 8.4 Hz,
6H), 7.41 (d, J = 8.4 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 137.8,
136.4, 130.3, 128.7; 29Si NMR (80 MHz, CDCl3) δ +1.1; HRMS (EI)
(M+) calcd for (C18H12Cl4Si+) 395.9456, observed 395.9460; IR (neat,
cm−1) 3041, 3020, 1915, 1575, 1482, 1381, 1186, 1119, 1083, 1014,
952, 813, 789, 735, 708.
Tris(4-fluorophenyl)silane (4d).62 Compound 4d was synthesized
using 1-fluoro-4-iodobenzene (2.22 g, 10 mmol) according to GP1.
The product was obtained as an oily liquid. After leaving for almost 2
days in the freezer at −20 °C, it became a colorless solid. The
compound was used for the next step without any further purification
(730 mg, yield = 77%): 1H NMR (400 MHz, CDCl3) δ 7.56−7.47 (m,
6H), 7.15−7.05 (m, 6H), 5.46 (s, 1H); 13C NMR (101 MHz, CDCl3)
δ 164.4 (d), 137.7 (d), 128.4 (d), 115.5 (d).
Chlorotris(4-fluorophenyl)silane(2d).63 Chlorination was done
using 4d (1.3 g, 4.13 mmol) according to GP3. The silane was
dissolved using 12 mL of carbon tetrachloride under nitrogen. Sulfuryl
chloride (670 μL, 9.90 mmol) was added to the reaction flask and
allowed to reflux for 4 h, resulting in an oil liquid after workup.
Pentane was added to the oily liquid which solubilized the final
product, while impurities remained undissolved. The pentane was
carefully separated from impurities and transferred to another vial
under nitrogen. The product was obtained through trituration at −78
°C using pentane to yield a colorless solid (500 mg, yield = 35%); 1H
NMR (400 MHz, CDCl3) δ 7.62−7.53 (m, 6H), 7.16−7.07 (m, 6H);
13C NMR (101 MHz, CDCl3) δ 164.8 (d), 137.4 (d), 128.1 (d), 115.6
(d).
General Procedure Making a p-Substituted Triphenylsilyl
Chloride. General Procedure 3 (GP3): An oven-dried 25−50 mL
three-neck round-bottom flask was charged with p-substituted
triphenylsilane and the mixture dissolved using dry degassed carbon
tetrachloride (CCl4) under a nitrogen atmosphere. The mixture was
allowed to stir for 10−15 min. Sulfuryl chloride (SO2Cl2) (2−6 equiv)
was then added to the flask. The resulting mixture was then allowed to
reflux for 4−28 h (conversion was monitored by disappearance of the
Tris(4-(trifluoromethyl)phenyl)silane (4e).41 The product was
synthesized using a Grignard method on a 30 mmol scale. Magnesium
metal was preactivated by leaving it in the oven for 24 h before use. In
a three-neck round-bottom flask, 750 mg of magnesium metal was
added and allowed to stir for 2 h under vacuum in order to activate.
After 2 h, 1-iodo-4-(trifluoromethyl)benzene (4.4 mL, 30 mmol) along
with 4.4 mL of ether were added to the flask. The resulting mixture
became a brown liquid which was allowed to stir for 10−15 min. After
15 min, 25 mL of ether was added to the flask and the mixture was
allowed to reflux for 30 min. After 30 min, the mixture was allowed to
cool to 0 °C and HSiCl3 (910 μL, 9 mmol, neat) was added to the
reaction mixture. The resulting mixture was allowed to stir for another
3 h (first 30 min at 0 °C and then at room temperature). After the
reaction was complete, the mixture was poured into a beaker
1
silane peak using H NMR). Hydrochloric acid generated during the
reaction was removed from the reaction mixture via a bubbler. The
excess solvent and other reagents were evaporated under vacuum (dry
ice cooled cold trap). The final product was then recrystallized or
triturated using an appropriate solvent under a N2 atmosphere.
Synthesis of p-Substituted Triphenylsilane and Silyl
Chlorides. Tris(4-bromophenyl)silane (4b).40 The product was
synthesized employing 1-bromo-4-iodobenzene (98%) (2.88 g, 10
mmol) according to GP1. The final colorless solid product was
obtained by recrystallization at −40 °C using pentane (1.16 g, yield =
2391
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
containing dry ice and dilute HCl. The reaction mixture was extracted
with ether and dried over anhydrous sodium sulfate. Excess ether was
removed under vacuum. A dark orange-brown oil was obtained. The
final product was obtained by vacuum distillation at 175−178 °C and 3
mmHg. A dark yellow liquid was obtained which was left under
vacuum to yield a colorless solid as the final product (1.1 g, yield =
26%): mp = 74−76 °C; 1H NMR (400 MHz, CDCl3) δ 7.68 (s, 12H),
5.58 (s, 1H); 13C NMR (101 MHz, CDCl3) δ 136.2, 136.0, 132.5 (q,
JCF = 33 Hz), 125 (q, J = 3.8 Hz), 123.9 (q, JCF = 273 Hz); 19F NMR
(377 MHz, CDCl3) δ −111.9; 29Si NMR (80 MHz) δ −18.7; HRMS
(EI) (M − H)+ calcd for (C21H12F9Si+) 463.0559, observed 463.0574;
IR (neat, cm−1) 2929, 2155, 1931, 1610, 1505, 1393, 1322, 1273, 1161,
1114, 1017, 844, 830, 793, 771, 722, 700.
GP2. After reaction completion, the solvent was removed under
vacuum. The crude product was obtained as an oil. Further purification
was done using column chromatography to yield an oil as the final
1
product (800 mg, yield = 77%): H NMR (400 MHz, CDCl3) δ 7.67
(d, J = 7.9 Hz, 6H), 7.36 (d, J = 7.7 Hz, 6H), 5.60 (s, 1H), 2.80 (q, J =
7.6 Hz, 6H), 1.39 (t, J = 7.6 Hz, 9H); 13C NMR (101 MHz, CDCl3) δ
145.8, 135.9, 130.5, 127.6, 28.9, 15.4; 29Si NMR (80 MHz, CDCl3) δ
−18.9; HRMS (EI) (M+) calcd for (C24H28Si+) 344.1954, observed
344.1960; IR (neat, cm−1) 3012, 2964, 2930, 2116, 1600, 1456, 1398,
1111, 1062, 967, 801, 772.
Chlorotris(4-ethylphenyl)silane (2h). Chlorination was done using
tris(4-ethylphenyl)silane (782 mg, 2.27 mmol) according to GP3.
Excess sulfuryl chloride (550 μL, 6.78 mmol) was used to achieve full
conversion in 4 h using 10 mL of carbon tetrachloride. The crude oily
liquid was further purified by trituration with hexanes at −40 °C under
a N2 atmosphere which resulted in a yellowish solid (455 mg, yield =
Chlorotris(4-(trifluoromethyl)phenyl)silane (2e). Chlorination was
done employing 4e (820 mg, 1.77 mmol) according to GP3. The
silane was dissolved in 8 mL of carbon tetrachloride followed by
addition of sulfuryl chloride (350 μL, 4.32 mmol). After 4 h, only 20%
1
53%): mp = 54−56 °C; H NMR (400 MHz, CDCl3) δ 7.56 (d, J =
1
conversion was observed from H NMR. Excess sulfuryl chloride was
8.1 Hz, 6H), 7.24 (d, J = 8.2 Hz, 6H), 2.67 (q, J = 7.6 Hz, 6H), 1.24 (t,
J = 7.6 Hz, 9H); 13C NMR (101 MHz, CDCl3) δ 146.9, 135.3, 130.0,
127.7, 28.9, 15.3; 29Si NMR (80 MHz, CDCl3) δ +1.6; HRMS (EI)
(M+) calcd for (C24H27ClSi+) 378.1565, observed 378.1573; IR (neat,
cm−1) 3012, 2967, 2933, 2873, 1600, 1456, 1397, 1272, 1190, 1115,
1062, 1020, 968, 796, 782.
added over the course of the reaction, but no further improvement in
conversion was observed after 48 h. Finally, the reaction mixture was
transferred to a microwave vessel equipped with a stir bar under an
argon atmosphere. The reaction vessel was then purged with argon
and sealed with a septa. The mixture was then microwaved for 40 min
at 120 °C employing 70 W. The mixture was allowed to cool to
ambient temperature and transferred to a 4 dram vial under an argon
atmosphere. The crude was concentrated under vacuum. The final
product was a yellowish solid (492 mg, yield = 56%), which was used
directly without any purification for the kinetic resolution. No
characterization was reported due to moisture sensitivity.
Tris(4-isopropylphenyl)silane (4i). Compound 4i was synthesized
using 4-bromoisopropyl benzene (95%) (1.63 mL, 10 mmol)
according to GP2. A colorless solid was obtained and purified further
by trituration at −40 °C with hexanes under a N2 atmosphere to get a
1
colorless powder (770 mg, yield = 66%): mp = 58−60 °C H NMR
(400 MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz, 6H), 7.23 (d, J = 7.9 Hz,
6H), 5.41 (s, 1H), 2.90 (m,3H), 1.25 (d, J = 6.9 Hz, 18H); 13C NMR
(101 MHz, CDCl3) δ 150.4, 135.9, 130.7, 126.2, 34.1, 23.8; 29Si NMR
(80 MHz, CDCl3) δ −18.8; HRMS (EI) (M+) calcd for (C27H34Si+)
386.2424, observed 386.2428; IR (neat, cm−1) 2961, 2928, 2110, 1924,
1598, 1458, 1392, 1297, 1265, 1117, 1094, 1049, 1019, 822, 794, 760,
725.
Tris(4-methoxyphenyl)silane (4f).62 The product was synthesized
using 4-iodoanisole (98%) (2.34 g, 10 mmol) according to GP1. A
colorless solid was obtained as the crude product. Silane was further
purified by carefully washing crude 2 times with distilled pentane (780
mg, yield = 74%): 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.6 Hz,
6H), 6.96 (d, J = 8.4 Hz, 6H), 5.46 (s, 1H), 3.85 (s, 9H); 13C NMR
(101 MHz, CDCl3) δ 160.9, 137.2, 124.8, 113.8, 55.0.
Chlorotris(4-isopropylphenyl)silane (2i).64 Chlorination was done
by using tris(4-isopropylphenyl)silane (875 mg, 2.26 mmol) according
to GP3. The silane was dissolved in 11 mL of carbon tetrachloride
followed by addition of sulfuryl chloride (550 μL, 6.78 mmol) under a
N2 atmosphere. The resulting mixture was allowed to reflux for 4 h to
achieve complete chlorination. After the reaction was complete, the
excess reagents were removed under vacuum. The crude product was
purify by trituration with hexanes at −40 °C under N2. A colorless
Chlorotris(4-methoxyphenyl)silane (2f). Chlorination was done
using 4f (300 mg, 0.86 mmol) according to GP3. The silane was
dissolved in 6 mL of carbon tetrachloride followed by addition of
sulfuryl chloride (139 μL, 1.72 mmol). Complete conversion was
achieved in 7−8 h. An oily liquid was obtained which became a light
yellow solid after scratching for almost an hour under nitrogen. This
solid was carefully washed with pentane to obtain the final product
(200 mg, yield = 60%): mp = 67−69 °C 1H NMR (400 MHz, CDCl3)
δ 7.57 (d, J = 8.7 Hz, 6H), 6.95 (d, J = 8.7 Hz, 6H), 3.84 (s, 9H); 13C
NMR (101 MHz, CDCl3) δ 161.5, 136.8, 124.4, 113.8, 55.1; 29Si NMR
(80 MHz, CDCl3) δ +1.2; HRMS (EI) (M+) calcd for
(C21H21ClO3Si+) 384.0943, observed 384.0952; IR (neat, cm−1)
3020, 2919, 2841, 1591, 1563, 1503, 1457, 1442, 1400, 1276, 1248,
1181, 1116, 1107, 1022, 817, 797, 659.
1
solid product was obtained (747 mg, yield = 78%): H NMR (400
MHz, CDCl3) δ 7.57 (d, J = 8.1 Hz, 6H), 7.27 (d, J = 7.4 Hz, 6H),
2.92 (septet, 3H), 1.26 (d, J = 6.9 Hz, 18H); 13C NMR (101 MHz,
CDCl3) δ 151.4, 135.3, 130.2, 126.2, 34.2, 23.8.
Tris(4-(tert-butyl)phenyl)silane (4j). Compound 4j was synthesized
using 1-bromo-4-tert-butylbenzene (98%) (1.76 mL, 10 mmol)
according to GP2. A colorless solid was obtained after washing the
crude solid with hexanes (1.27 g, yield = 99%): mp = 169−171 °C; 1H
NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.2 Hz, 6H), 7.40 (d, J = 8.2
Hz, 6H), 5.42 (s, 1H), 1.32 (s, 27H); 13C NMR (101 MHz, CDCl3) δ
152.6, 135.7, 130.2, 124.9, 34.7, 31.2; 29Si NMR (80 MHz, CDCl3) δ
−18.9; HRMS (EI) (M+) calcd for (C30H40Si+) 428.2893, observed
428.2894; IR (neat, cm−1) 2960, 2868, 2108, 1596, 1463, 1387, 1362,
1267, 1137, 1085, 822, 788, 724.
Tri-p-tolylsilane (4g).62 The product was synthesized using 4-
iodotoluene (2.18 g, 10 mmol) according to GP1. A colorless solid was
formed which was further recrystallized using pentane at −40 °C (770
mg, yield = 85%): 1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 7.8 Hz,
6H), 7.18 (d, J = 7.6 Hz, 7H), 5.43 (s, 1H), 2.35 (s, 9H); 13C NMR
(101 MHz, CDCl3) δ 139.6, 135.8, 130.1, 128.8, 21.5.
Chlorotri-p-tolylsilane (2g). Chlorination was done using tri-p-
tolylsilane (1.03 g, 3.4 mmol) according to GP3. The silane was
dissolved in 17 mL of carbon tetrachloride followed by addition of
sulfuryl chloride (550 μL, 6.8 mmol). It took 7−8 h to achieve
complete conversion. The final product was obtained through
recrystallization from hexanes at −40 °C to obtain a colorless solid
Tris(4-(tert-butyl)phenyl)chlorosilane (2j).64 Chlorination was
done using tris(4-(tert-butyl)phenyl)silane (1.26 g, 2.93 mmol)
according to GP3. The silane was dissolved in 12 mL of carbon
tetrachloride followed by addition of sulfuryl chloride (710 μL,8.79
mmol). The crude solid was purified by washing 2−3 times with
1
1
(590 mg, yield = 51%): mp = 110−112 °C; H NMR (400 MHz,
hexanes to obtain a colorless solid (850 mg, yield = 63%): H NMR
CDCl3) δ 7.52 (d, J = 7.6 Hz, 6H), 7.22 (d, J = 7.6 Hz, 6H), 2.38 (s,
9H); 13C NMR (101 MHz, CDCl3) δ 140.7, 135.2, 129.7, 128.9, 21.6;
29Si NMR (80 MHz, CDCl3) δ +1.8; HRMS (EI) (M+) calcd for
(C21H21ClSi+) 336.1095, observed 336.1096; IR (neat, cm−1) 3019,
2921, 2862, 1924, 1598, 1501, 1393, 1312, 1190, 1114, 1021, 712.
Tris(4-ethylphenyl)silane (4h). Compound 4h was synthesized
using 1-ethyl-4-iodobenzene (98%) (1.48 mL, 10 mmol) according to
(400 MHz, CDCl3) δ 7.59 (d, J = 8.3 Hz, 6H), 7.43 (d, J = 8.3 Hz,
6H), 1.32 (s, 27H); 13C NMR (101 MHz, CDCl3) δ 153.6, 135.1,
129.8, 125.0, 34.8, 31.2.
Tris(4-cyclohexylphenyl)silane (4k). Compound 4k was synthe-
sized using 1-bromo-4-cyclohexylbenzene (98%) (1.89 mL, 10 mmol)
according to GP2. The crude solid was recrystallized from pentane at
−40 °C to yield a colorless solid (1.30 g, yield = 86%): mp = 79−81
2392
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
°C; 1H NMR (400 MHz, CDCl3) 7.52 (d, J = 8.0 Hz, 6H), 7.22 (d, J =
8.0 Hz, 6H), 5.41 (s, 1H), 2.53−247 (m, 3H), 1.91−1.82 (m, 12H),
1.77−1.73 (m, 3H), 1.45−1.34 (m, 12H), 1.31−1.24 (m, 3H); 13C
NMR (101 MHz, CDCl3) δ 149.6, 135.8, 130.7, 126.6, 44.6, 34.3, 26.9,
26.1; 29Si NMR (80 MHz, CDCl3) δ −18.8; HRMS (EI) (M+) calcd
for (C36H46Si+) 506.3363, observed 506.3352; IR (neat, cm−1) 3011,
2922, 2850, 2122, 1598, 1447, 1400, 1263, 1111, 998, 891, 866, 772,
727, 687, 671.
Chlorotris(4-cyclohexylphenyl)silane (2k). Chlorination was done
using tris(4-cyclohexylphenyl)silane (1.26 g, 2.49 mmol) according to
GP3. The silane was dissolved in 6 mL of carbon tetrachloride
followed by the addition of sulfuryl chloride (602 μL, 7.47 mmol).
Product formation was complete in 4 h. The crude oil was triturated
with pentane at −78 °C under N2, resulting in a colorless solid (500
mg, yield = 37%): mp = 123−124 °C; 1H NMR (400 MHz, CDCl3) δ
7.57 (d, J = 8.2 Hz, 6H), 7.24 (d, J = 7.9 Hz, 6H), 2.53−2.51 (m, 3H),
1.90−1.83 (m, 12H), 1.77−1.73 (m, 3H), 1.47−1.34 (m, 12H), 1.30−
1.23 (m, 3H); 13C NMR (101 MHz, CDCl3) δ 150.6, 135.3, 130.2,
126.6, 44.6, 34.2, 26.8, 26.1; 29Si NMR (80 MHz, CDCl3) δ +1.5;
HRMS (EI) (M+) calcd for (C36H45ClSi+) 540.2973, observed
540.2971; IR (neat, cm−1) 3014, 2923, 2850, 1599, 1447, 1400,
1263, 1116, 998, 817, 673.
relationship between concentration and absorbance was constructed
by calculating the product concentration from the NMR conversions
and plotting it against the absorbance at each of those time points.
Once the Beer’s Law relationship was determined, the concentration at
each data point was calculated from the absorbance and plotted against
time to determine the rate. Initial rate was determined by using the
data up to 10% conversion. The accuracy of the peak obtained from
ConcIRT was confirmed by comparing the NMR conversion with the
calculated conversion from the absorbance.
General Procedure for the Silylation-Based Kinetic Reso-
lution of Secondary Alcohols and Desilylation of the Isolated
Products. An oven-dried 1 dram vial was charged with 4 Å molecular
sieves (10−15 mg) and a Teflon-coated stir bar. The racemic alcohol
(5 or 7) (0.22 mmol), catalyst 1 (11.2 mg, 0.055 mmol), and N,N-
diisopropylethylamine (Hunig’s base) (23 μL, 0.132 mmol) were
̈
added to a vial and then quickly sealed under a nitrogen atmosphere.
Dry THF (1.0 mL) was added, and the reaction mixture was allowed
to stir at −78 °C for 15−20 min. Meanwhile, a solution of (pY-
Ph)3SiCl (0.357 M) was prepared using a volumetric flask (under N2).
The solution of (pY-Ph)3SiCl 2 (370 μL, 0.6 mmol) was added to the
reaction vial, and the resulting mixture was allowed to react for the
specified amount of time at −78 °C. The reaction mixture was then
quenched using 300 μL of MeOH at −78 °C. The mixture was
allowed to warm to room temperature followed by addition of 1.0 mL
of saturated aqueous NH4Cl. The reaction mixture was transferred to a
4 dram vial and extracted using diethyl ether (3 × 2 mL). The ether
layer was then passed through a pad of silica gel. After filtration, it was
concentrated and the crude mixture was purified using silica gel
chromatography (100% CH2Cl2 followed by 2% MeOH in CH2Cl2).
The analysis of the unreacted recovered alcohol was done by a chiral
HPLC using a hexanes/i-PrOH solvent system.
Tris([1,1′-biphenyl]-4-yl)silane (4l). Compound 4l was synthesized
using 4-iodobiphenyl (97%) (2.89 g, mmol) according to GP2.
Addition of SiHCl3 after lithiation was done at −78 °C instead of −40
°C and allowed to stir for 2 h. The crude white solid was carefully
filtered and used without further purification (1.35 g, yield = 92%): mp
1
= 192−193 °C H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.3 Hz,
6H), 7.67−7.61 (m, 12H), 7.46 (t, J = 7.3 Hz, 6H), 7.37 (t, J = 7.4 Hz,
3H), 5.60 (s, 1H); 13C NMR (101 MHz, CDCl3) δ 142.6, 140.9,
136.3, 132.0, 128.8, 127.6, 127.2, 126.9; 29Si NMR (80 MHz, CDCl3)
δ −18.4; HRMS (EI) (M+) calcd for (C36H28Si+) 488.1954, observed
488.1959; IR (neat, cm−1) 3011, 2106, 1595, 1542, 1481, 1384, 1182,
1115, 1007, 845, 835, 763, 755, 660.
Desilylation. The silylated product was transferred to a 4 dram vial
with a stir bar and dissolved in 3 mL of THF. The solution was treated
with a 1 M solution of TBAF in THF (500 μL to 1.0 mL) and allowed
to stir for 3−10 h at room temperature (conversion was monitored by
TLC). The reaction was quenched with brine and extracted with
diethyl ether. The crude mixture was purified via silica gel column
chromatography (CH2Cl2 to 2% MeOH in CH2Cl2). HPLC analysis
was done for the desilylated product (alcohol). The absolute
stereochemistry was confirmed by comparing the HPLC data with
previously published data.9
Tris([1,1′-biphenyl]-4-yl)chlorosilane (2l). Chlorination was done
using tris([1,1′-biphenyl])4-yl)silane (4l) (1.43 g, 2.92 mmol)
according to GP3. Carbon tetrachloride (14 mL) was added, and
the solution was heated in order to dissolve the compound. Sulfuryl
chloride (708 μL, 8.76 mmol) was added and refluxed for 4 h. The
crude solid was washed with hexanes 2−3 times, resulting in a light
1
pink product (800 mg, yield = 52%): mp = 215−217 °C; H NMR
(400 MHz, CDCl3) δ 7.79 (d, J = 8.3 Hz, 6H), 7.68 (d, J = 8.3 Hz,
6H), 7.63 (d, J = 8.2 Hz, 6H), 7.47 (t, J = 7.2 Hz, 6H), 7.40−7.36 (m,
3H); 13C NMR (101 MHz, CDCl3) δ 143.5, 140.6, 135.7, 131.5,
128.9, 127.8, 127.2, 126.9; HRMS (EI) (M+) calcd for (C36H27ClSi+)
522.1565, observed 522.1580.
HPLC Conditions for 1,2,3,4-Tetrahydronaphthalen-1-ol (5).9
Chiralpack OD-H column was used with 4% iPrOH in hexanes.
Flow rate was 0.5 mL/min, 25 °C; tR 25.2 min for (S)-enantiomer and
tR 28.7 min for (R)-enantiomer.
HPLC Conditions for 4-Chromanol (7).9 Chiralpack OD-H column
was used with 2% iPrOH in hexanes. Flow rate was 1.3 mL/min, 25
°C; tR 28.6 min for (S)-enantiomer and tR 37.3 min for (R)-
enantiomer.
General Procedure of Rate Study Using In Situ IR. All reactions
were carried out at 0.08 M concentration with regard to the alcohol. A
three-neck 50 mL Schlenk tube with a 24/40 ground glass joint for
probe insertion with two side arms used as a reaction vessel. A probe
was inserted into the Schlenk tube equipped with a stir bar under N2
atmosphere. After the instrument was calibrated, an air background
was taken first. THF (2.10 mL) was added to the Schlenk tube, and
the solvent was allowed to cool to −78 °C for approximately 20 min
using a dry ice/acetone bath. The solvent background was recorded for
each experiment at −78 °C, then IR data collection was started. A
1,2,3,4-Tetrahydronaphthalen-1-ol (5): 1H NMR (400 MHz,
CDCl3) δ ppm 7−44−7.23 (m, 1 H), 7.22−7.20 (m, 2 H), 7.12−
7.10 (m, 1H) 4.79 (t, 5.0 Hz, 1H), 2.87−2.81 (m, 1 H), 2.77−2.69 (m,
1H), 2.01−1.88 (m, 3 H), 1.83−1.75(m, 2H); 13C NMR (101 MHz,
CDCl3) δ ppm 138.7, 137.1, 129.0, 128.6, 127.5, 126.1, 68.1, 32.2,
29.2, 18.7.
Triphenyl((1,2,3,4-tetrahydronaphthalen-1-yl)oxy)silane (6a):9
1
solution of (R)-5 or (S)-5 (54.3 mg), 1 (38 mg), and Hunig’s base (64
̈
33.5 mg (yield = 37%), white solid; H NMR (400 MHz, CDCl3) δ
μL) was prepared in a 1 mL volumetric flask. From the above prepared
solution, 810 μL was carefully added to the Schlenk tube via a syringe.
The resulting mixture was allowed to stir for 10−15 min. Meanwhile, a
solution of 2 (0.357 M) was prepared using a volumetric flask, and 840
μL of this was added to the reaction mixture at −78 °C. The time of
the silyl chloride addition was recorded for reference, and IR data were
collected for 30 min to 10 h. Rapid collect was used for data collection
in the case of electron withdrawing p-substituted triphenylsilyl chloride
rate experiments. The absorbance was obtained using ConcIRT.
Reaction conversion was obtained at different time points by taking
reaction aliquots at these time points, quenching them, and
7.68 (d, J = 6.0 Hz, 6H), 7.47−7.36 (m, 9H), 7.28(d, J = 6.8 Hz, 1H),
7.18−7.06 (m, 3H), 4.97 (t, J = 5.6 Hz, 1H), 2.88−2.81 (m, 1H),
2.72−2.64 (m, 1H), 2.10−2.03 (m, 1H), 1.96−1.82 (m, 2H), 1.72−
1.63 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 138.9, 137.0, 135.6,
134.8, 129.9, 128.7, 128.6, 127.8, 127.1, 125.7, 70.2, 32.5, 29.0, 19.2.
(R)-Tris(4-bromophenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)-
oxy)silane (6b): 55 mg (yield = 39%), white solid; mp range 88−89
°C; 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.2 Hz, 6H), 7.46 (d, J
= 8.1 Hz, 6H), 7.21−7.14 (m, 2H), 7.13−7.06 (m, 2H), 4.94 (t, J = 5.0
Hz, 1H), 2.88−2.81 (m, 1H), 2.74−2.66 (m, 1H), 2.14−2.01 (m, 1H),
1.97−1.79 (m, 2H), 1.77−1.64 (m, 1H); 13C NMR (101 MHz,
CDCl3) δ 138.1, 137.1, 136.9, 132.6, 131.3, 128.9, 128.5, 127.5, 125.7,
125.5, 70.6, 32.5, 28.9, 18.9; [α]D25 = +19.0 (c = 0.75, CHCl3); HRMS
1
determining the conversion by H NMR. The geminal proton of the
product and the starting material were used for integration. The
2393
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
25
(EI) (M+) calcd for (C28H23Br3OSi+) 641.9043, observed 641.9034;
IR (neat, cm−1) 3069, 2937, 2866, 1739, 1572, 1550, 1478, 1454, 1377,
1350, 1208, 1185, 1115, 1066, 1009, 988, 906, 807, 757.
128.6, 127.4, 126.9, 125.6, 70.0, 32.6, 29.1, 28.9, 19.3, 15.3; [α]D
=
+18.0 (c = 0.70, CHCl3); HRMS (EI) (M+) calcd for (C34H38OSi+)
490.2686, observed 490.2691; IR (neat, cm−1) 3066, 2964, 2932, 2872,
1601, 1553, 1455, 1398, 1190, 1072, 1039, 1017, 988, 821, 783, 739.
(R)-Tris(4-isopropylphenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)-
(R)-Tris(4-chlorophenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)oxy)-
silane (6c): 34.9 mg (yield = 31%), colorless oil with minor amounts
of tris(4-chlorophenyl)silanol present; 1H NMR (400 MHz, CDCl3) δ
7.52 (d, J = 8.4 Hz, 6H), 7.38 (d, J = 8.4 Hz, 6H), 7.21−7.13 (m, 2H),
7.13−7.06 (m, 2H), 4.94 (m, 1H), 2.88−2.80 (m, 1H), 2.73−2.65(m,
1H), 2.12−2.02 (m, 1H), 1.95−1.78 (m, 2H), 1.75−1.65 (m, 1H); 13C
NMR (101 MHz, CDCl3) δ 138.2, 137.1, 136.8, 136.7, 132.3, 128.9,
1
oxy)silane (6i): 40.7 mg (yield = 35%), colorless oil; H NMR (400
MHz, CDCl3) δ 7.60 (d, J = 8.2 Hz, 6H), 7.28 (d, J = 7.0 Hz, 1H),
7.22 (d, J = 7.8 Hz, 6H), 7.15−7.08 (m, 2H), 7.05−7.03 (m, 1H), 4.93
(t, J = 6.2 Hz, 1H), 2.93−2.79 (m, 4H), 2.70−2.62(m, 1H), 2.10−2.00
(m, 1H), 1.95−1.82 (m, 2H), 1.70−1.59 (m, 1H), 1.25 (d, J = 8.0 Hz,
18H); 13C NMR (101 MHz, CDCl3) δ 150.4, 139.3, 137.0, 135.7,
132.2, 128.7, 128.6, 126.9, 125.9, 125.6, 70.0, 34.1, 32.6, 29.1, 23.9,
25
128.6, 128.4, 127.4, 125.7, 70.6, 32.5, 28.9, 18.9; [α]D = +22.6 (c =
0.88, CHCl3); HRMS (EI) (M+) calcd for(C28H23Cl3OSi+) 508.0578,
observed 508.0558; IR (neat, cm−1) 3072, 2936, 1913, 1578, 1556,
1482, 1455, 1381, 1349, 1257, 1184, 1118, 1082, 1014, 989, 877, 812,
711.
25
19.3; [α]D = +16.8 (c = 0.95, CHCl3); HRMS (EI) (M+) calcd for
(C37H44OSi+) 532.3155, observed 532.3139; IR (neat, cm−1) 3067,
2959, 2869, 1920, 1600, 1491, 1458, 1394, 1362, 1263, 1119, 1072,
1050, 1018, 988, 849, 769, 739, 710.
(R)-Tris(4-fluorophenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)oxy)-
silane (6d): 38.0 mg (yield = 38%), colorless oil; 1H NMR (400 MHz,
CDCl3) δ 7.64−7.59 (m, 6H), 7.21−7.17 (m, 2H), 7.14−7.08 (m,
8H), 4.96 (t, J = 5.6 Hz, 1H), 2.89−2.82 (m, 1H), 2.74−2.67 (m, 1H),
2.14−2.04 (m, 1H), 1.96−1.81 (m, 2H), 1.76−1.66 (m, 1H); 13C
NMR (101 MHz, CDCl3) δ 165.6−163.1(d), 138.4, 137.6−137.5 (d),
137.1, 130.0(d), 128.9, 128.6, 127.4, 125.7, 115.4−115.2 (d), 70.4,
32.5, 28.9, 19.0; [α]D25 = +18.0 (c = 0.91, CHCl3); HRMS (EI) (M+)
calcd for (C28H23F3OSi+) 460.1464, observed 460.1454; IR (neat,
cm−1) 3025, 2937, 1910, 1588, 1498, 1388, 1350, 1225, 1161, 1110,
1070, 1014, 989, 878, 755, 738, 715.
(R)-Tris(4-(tert-butyl)phenyl)((1,2,3,4-tetrahydronaphthalen-1-
yl)oxy)silane (6j): 48.5 mg (yield = 38%), white solid; mp 137−139
°C; 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.4 Hz, 6H), 7.39 (d, J
= 8.4 Hz, 6H), 7.29 (d, J = 7.4 Hz, 1H), 7.17−7.10 (m, 2H), 7.08−
7.05 (m, 1H), 4.95 (t, J = 6.2 Hz, 1H), 2.88−2.81 (m, 1H), 2.71−2.68
(m,1H), 2.11−2.02 (m, 1H), 1.98−1.84 (m, 2H), 1.72−1.63 (m, 1H),
1.33 (s, 27H). 13C NMR (101 MHz, CDCl3) δ 152.6, 139.4, 137.0,
135.5, 131.7, 128.7, 128.6, 126.9, 125.6, 124.6, 69.9, 34.7, 32.6, 31.2,
25
29.1, 19.3; [α]D = +19.4 (c = 1.1, CHCl3); HRMS (EI) (M+) calcd
for (C40H50OSi+) 574.3625, observed 574.3633; IR (neat, cm−1) 2961,
2867, 1984, 1599, 1459, 1388, 1362, 1268, 1203, 1138, 1017, 988, 926,
876, 824, 750.4.
(R)-((1,2,3,4-Tetrahydronaphthalen-1-yl)oxy)tris(4-(trifluoro-
methyl)phenyl)silane (6e): 33.1 mg (yield = 25%), colorless oil with
1
minor amounts of tris(4-(trifluoromethyl)phenyl)silanol present; H
(R)-Tris(4-cyclohexylphenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)-
oxy)silane (6k): 37.2 mg (yield = 26%), colorless oil; H NMR (400
1
NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.2 Hz, 6H), 7.66 (d, J = 8.2
Hz, 6H), 7.21−7.17 (m, 1H), 7.14−7.08 (m, 3H), 5.00 (t, J = 5.1,
1H), 2.88−2.81 (m, 1H), 2.75−2.67 (m, 1H), 2.16−2.06 (m, 1H),
1.97−1.83 (m, 2 H), 1.78−1.69 (m, 1H); 13C NMR (101 MHz,
CDCl3) δ 138.1, 137.7, 137.2, 135.7,, 132.5 (q, JCF = 32.4 Hz), 129.1,
MHz, CDCl3) δ 7.58(d, J = 8.0 Hz, 6H), 7.26 (d, J = 7.5 Hz, 1H), 7.19
(d, J = 7.9 Hz, 6H), 7.15−7.03 (m, 3H), 4.92 (t, J = 6.0 Hz, 1 H),
2.86−2.78 (m, 1H), 2.69−2.62 (m, 1H), 2.52−2.46 (m, 3H), 2.09−
1.99 (m, 1H), 1.93−1.81 (m, 14H), 1.75−1.72 (m, 3 H), 1.69−1.63
(m, 1 H), 1.51−1.33 (m, 12H), 1.28−1.20 (m, 3 H); 13C NMR (101
128.6, 127.7, 125.8, 124.8 (q, JCF = 3.8 Hz), 124.0 (q, J = 272.5 Hz),
25
71.1, 32.5, 28.8, 18.8; 19F NMR (377 MHz, CDCl3) δ −63.1; [α]D
=
MHz, CDCl3) δ 149.6, 139.4, 137.0, 135.7, 132.2, 128.7, 128.6, 126.9,
25
+9.7 (c = 0.67, CHCl3); HRMS (EI) (M+) calcd for (C31H23F9OSi+)
610.1368, observed 610.1372; IR (neat, cm−1) 3031, 2939, 1610, 1393,
1318, 1164, 1121, 1017, 990, 829, 739, 704.
126.3, 125.6, 69.9, 44.6, 34.3, 32.6, 29.1, 26.9, 26.2, 19.3; [α]D
=
+14.3 (c = 1.04, CHCl3); HRMS (EI) (M+) calcd for (C46H56OSi+)
652.4094, observed 652.4094; IR (neat, cm−1) 3066, 2923, 2851, 1923,
1600, 1448, 1397, 1350, 1263, 1115, 1072, 999, 1016, 988, 815, 755,
738, 668.
(R)-Tris(4-methoxyphenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)-
1
oxy)silane (6f): 21.3 mg (yield = 20%), colorless oil; H NMR (400
MHz, CDCl3) δ 1H 7.58 (d, J = 8.7 Hz, 6H), 7.27 (m, 1H), 7.17−7.11
(m, 2H), 7.09−7.05 (m, 1H), 6.93(d, J = 8.7 Hz, 6H), 4.94 (t, J = 6.0
Hz, 1H), 3.83 (s, 9H), 2.87−2.80 (m, 1H), 2.71−2.64 (m,1H), 2.09−
2.01 (m, 1H), 1.92−1.82 (m, 2H), 1.71−1.62 (m, 1H); 13C NMR
(101 MHz, CDCl3) δ 160.9, 139.3, 137.1, 137.0, 128.7, 128.6, 127.0,
(R)-Tri([1,1′-biphenyl]-4-yl)((1,2,3,4-tetrahydronaphthalen-1-yl)-
oxy)silane (6l): 27.2 mg (yield = 19%), white solid; mp 44−46 °C; 1H
NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.2 Hz, 6H), 7.65−7.62 (m,
12H), 7.45−7.43 (m, 6H), 7.37−7.33 (m, 4H), 7.19−7.13 (m, 2H),
7.11−7.07 (m, 1H), 5.07 (t, J = 6.2 Hz, 1H), 2.91−2.83 (m, 1H),
2.74−2.66 (m, 1H), 2.17−2.07 (m, 1H), 2.04−1.88 (m, 2H), 1.76−
1.65 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 142.6, 140.9, 138.9,
137.1, 136.1, 135.9, 133.5, 128.9, 128.8, 128.7, 127.5, 127.2, 126.6,
125.7, 70.4, 32.6, 29.1, 19.2; [α]D25 = +23.3 (c = 0.94, CHCl3); HRMS
(EI) (M+) calcd for (C46H38OSi+) 634.2686, observed 634.2673; IR
(neat, cm−1) 3059, 3024, 2934, 1809, 1597, 1544, 1483, 1446, 1386,
1255, 1117, 1071, 1006, 988, 829, 756, 695.
25
126.4, 125.6, 113.5, 69.9, 55.0, 32.6, 29.1, 19.3; [α]D = +13.1 (c =
0.95, CHCl3); HRMS (EI) (M+) calcd for (C31H32O4Si+) 496.2064,
observed 496.2053; IR (neat, cm−1) 3062, 2934, 2836, 1903, 1592,
1563, 1501, 1456, 1441, 1277, 1246, 1179, 1070, 1028, 987, 909, 814,
798, 733.
(R)-((1,2,3,4-Tetrahydronaphthalen-1-yl)oxy)tri-p-tolylsilane (6g):
1
43.4 mg (yield = 44%), colorless oil; H NMR (400 MHz, CDCl3) δ
1
Chroman-4-ol (7): H NMR (400 MHz, CDCl3) δ 7.31(d, J = 7.6
7.55 (d, J = 8.0 Hz, 6H), 7.30 (d, J = 8.5 Hz, 1H), 7.18 (d, J = 8.0 Hz,
6H), 7.14−7.09 (m, 2H), 7.08−7.04 (m, 1H), 4.93 (t, J = 5.6 Hz, 1H),
2.85−2.79 (m, 1H), 2.69−2.62 (m, 1H), 2.35 (s, 9H), 2.08−1.99
(m,1H), 1.92−1.82 (m, 2H), 1.69−1.60 (m, 1H); 13C NMR (101
MHz, CDCl3) δ 139.7, 139.3, 137.0, 135.6, 135.4, 131.6, 128.8, 128.6,
Hz, 1H), 7.23−7.19 (m, 1H), 6.95−6.91 (m,1H), 6.85 (d, J = 8.2 Hz,
1H),4.79 (t, J = 3.9 Hz, 1H), 4.32−2.25 (m, 2H), 2.17−2.09 (m, 1H),
2.07−2.01 (m, 1H), 1.86 (s,1H); 13C NMR (101 MHz, CDCl3) δ
154.5, 129.7, 129.6, 124.3, 120.6, 117.0, 63.2, 61.9, 30.8.
(Chroman-4-yloxy)triphenylsilane (8a):9 white solid, 35.5 mg
25
126.9, 125.6, 70.0, 32.6, 29.1, 21.6, 19.3; [α]D = +16.2 (c = 0.98,
1
CHCl3); HRMS (EI) (M+) calcd for (C31H32OSi+) 448.2216,
observed 448.2217; IR (neat, cm−1) 3066, 2936, 2864, 1920, 1739,
1599, 1501, 1451, 1393, 1350, 1261, 1208, 1188, 1111, 1071, 1016,
988, 876, 738, 715.
(yield = 40%); H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 6.5 Hz,
6H), 7.48−7.37 (m, 9H), 7.18−7.14 (m, 1H), 6.99 (d, J = 7.2 Hz,
1H), 6.83−6.76 (m, 2H), 4.97 (t, J = 4.0 Hz, 1H), 4.51−4.45 (m, 1H),
4.24−4.19 (m, 1H), 2.02−1.96 (m, 2H); 13C NMR (101 MHz,
CDCl3) δ 154.5, 135.5, 134.3, 130.1, 130.0, 129.2, 127.8, 124.2, 120.0,
116.7, 65.0, 62.2, 31.4.
(R)-Tris(4-bromophenyl)(chroman-4-yloxy)silane (8b): 49.3 mg
(yield = 35%), white solid; mp 109−110 °C, H NMR (400 MHz,
CDCl3) δ 7.52 (d, J = 8.1 Hz, 6H), 7.43 (d, J = 8.2 Hz, 6H), 7.20−7.16
(m, 1H), 6.89 (d, J = 7.6 Hz, 1H), 6.83−6.76 (m, 2H), 4.92 (t, J = 4.0
Hz, 1H), 4.47−4.40 (m, 1H), 4.26−4.21 (m, 1H), 2.01−1.97 (m, 2H);
(R)-Tris(4-ethylphenyl)((1,2,3,4-tetrahydronaphthalen-1-yl)oxy)-
silane (6h): 33.3 mg (yield = 31%), colorless oil; 1H NMR (400 MHz,
CDCl3) δ 7.59 (d, J = 8.1 Hz, 6H), 7.29 (d, J = 7.4 Hz, 1H), 7.20 (d, J
= 8.2 Hz, 6H), 7.15−7.09 (m, 2H), 7.07−7.03 (m, 1H), 4.93 (t, J = 6.1
Hz, 1H), 2.86−2.79 (m, 1H), 2.63−2.70 (m, 7H), 2.09−2.00 (m, 1H),
1.94−1.81 (m, 2H), 1.70−1.60 (m, 1H), 1.24 (t, J = 7.6 Hz, 9H); 13C
NMR (101 MHz, CDCl3) δ 145.9, 139.3, 137.0, 135.7, 132.0, 128.7,
1
2394
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
13C NMR (101 MHz, CDCl3) δ 154.5, 136.8, 132.2, 131.4, 129.8,
129.6, 125.7, 123.3, 120.1, 116.9, 65.4, 61.9, 31.3; [α]D25 = +38.3 (c =
0.84, CHCl3); HRMS (EI) (M+) calcd for (C27H21Br3O2Si+)
643.8836, observed 643.8859; IR (neat, cm−1) 3071, 2926, 1915,
1610, 1572, 1478, 1377, 1224, 1116, 1063, 1008, 906, 806, 753.
(R)-Tris(4-chlorophenyl)(chroman-4-yloxy)silane (8c): 46.6 mg
(R)-(Chroman-4-yloxy)tris(4-isopropylphenyl)silane (8i): 41.2 mg
(yield = 35%), white solid; mp 90−92 °C; 1H NMR (400 MHz,
CDCl3) δ 7.58 (d, J = 7.8 Hz, 6H), 7.23 (d, J = 7.9 Hz, 6H), 7.13 (t, J
= 8.1 Hz, 1H), 6.94 (d, J = 7.3 Hz, 1H), 6.79−6.73 (m, 2H), 4.93 (t, J
= 4.2 Hz, 1H), 4.49−4.43 (m, 1H), 4.19 (dt, J = 6.3, 4.2 Hz, 1H), 2.91
(hept, J = 6.9 Hz, 3H), 2.05−1.90 (m, 2H), 1.25 (d, J = 6.9 Hz, 18H);
13C NMR (101 MHz, CDCl3) δ 154.5, 150.6, 135.6, 131.7, 130.1,
1
(yield = 41%), yellowish color oil; H NMR (400 MHz, CDCl3) δ
25
7.51 (d, J = 8.3 Hz, 6H), 7.41 (d, J = 8.3 Hz, 6H), 7.20−7.16 (m, 1H),
6.91−6.89 (m,1H), 6.84−6.76 (m, 2H), 4.94 (t, J = 4.4 Hz, 1H),
4.48−4.42 (m, 1H), 4.27−4.22 (m, 1H), 2.01−1.97 (m, 2H); 13C
NMR (101 MHz, CDCl3) δ 153.5, 136.1, 135.7, 130.9, 128.9, 128.6,
129.0, 126.0, 124.5, 119.9, 116.6, 64.7, 62.3, 34.1, 31.5, 23.8; [α]D
=
+50.8 (c = 0.90, CHCl3); HRMS (EI) (M+) calcd for (C36H42O2Si+)
534.2948, observed 534.2942; IR (neat, cm−1) 3067, 2960, 2870, 1738,
1600, 1585, 1489, 1456, 1394, 1268, 1226, 1118, 1092, 1051, 1004,
922, 822, 809, 770, 754, 720.
25
127.5, 122.4, 119.1, 116.0, 64.4, 60.9, 30.4; [α]D = +49.9 (c = 1.17,
CHCl3); HRMS (EI) (M+) calcd for (C27H21Cl3O2Si+) 510.0370,
observed 510.0363; IR (neat, cm−1) 3072, 2927, 1912, 1609, 1578,
1482, 1381, 1224, 1118, 1082, 1014, 924, 809, 711.
(R)-Tris(4-(tert-butyl)phenyl)(chroman-4-yloxy)silane (8j): 47.5
mg (yield = 37%), white solid; mp 112−114 °C; 1H NMR (400
MHz, CDCl3) δ 7.60 (d, J = 8.1 Hz, 6H), 7.40 (d, J = 8.1 Hz, 6H),
7.14 (t, J = 7.6 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 6.81−6.74 (m, 2H),
4.94 (t, J = 4.0 Hz, 1H), 4.50−4.44 (m, 1H), 4.23−4.18 (m, 1H),
2.07−1.92 (m, 2H), 1.33 (s, 27H); 13C NMR (101 MHz, CDCl3) δ
154.5, 152.8, 135.4, 131.3, 130.1, 129.0, 124.8, 124.6, 119.9, 116.6,
64.7, 62.3, 34.8, 31.5, 31.2; [α]D25 = +49.5 (c = 1.13, CHCl3); HRMS
(EI) (M+) calcd for (C39H48O2Si+) 576.3418, observed 576.3429; IR
(neat, cm−1) 3073, 2963, 2868, 1927, 1600, 1583, 1487, 1453, 1388,
1268, 1252, 1140, 1125, 1065, 1004, 918, 824, 809, 751.
(R)-(Chroman-4-yloxy)tris(4-fluorophenyl)silane (8d): 37 mg
1
(yield = 36%), colorless oil; H NMR (400 MHz, CDCl3) δ 7.60−
7.56 (m, 6H), 7.20−7.15 (m, 1H), 7.13−7.08 (m, 6H), 6.89 (d, J = 7.6
Hz, 1H), 6.83−6.76 (m, 2H), 4.94 (t, J = 4.0 Hz, 1H), 4.49−4.42 (m,
1H), 4.27−4.21 (m, 1H), 2.01−1.97 (m, 2H); 13C NMR (101 MHz,
CDCl3) δ 165.7−163.2 (d), 154.5, 137.5 (d), 129.8, 129.6(d), 129.5,
25
123.6, 120.0, 116.9, 115.5−115.3(d), 65.2, 62.0, 31.4; [α]D = +47.4
(c = 0.98, CHCl3); HRMS (EI) (M+) calcd for (C27H21F3O2Si+)
462.1257, observed 462.1266; IR (neat, cm−1) 3065, 2928, 2888, 1909,
1610, 1498, 1489, 1388, 1269, 1223, 1161, 1110, 1092, 1064, 1003,
924, 821, 754, 715.
(R)-(Chroman-4-yloxy)tris(4-cyclohexylphenyl)silane (8k): 52.2
1
mg (yield = 36%), white solid; mp 47−49 °C; H NMR (400 MHz,
CDCl3) δ 7.57 (d, J = 8.0 Hz, 6H), 7.22 (d, J = 8.0 Hz, 6H), 7.15−7.11
(m, 1H), 6.95−9.92 (m, 1H), 6.80−6.73 (m, 2H), 4.92 (t, J = 4.3 Hz,
1 H), 4.49−4.43 (m, 1 H), 4.22−4.17 (m, 1H), 2.53−2.48 (m, 3H),
2.05−1.93 (m, 2H), 1.90−1.48 (m, 12H), 1.76−1.73 (m, 3H), 1.48−
1.34 (m, 12H), 1.30−1.23 (m, 3H); 13C NMR (101 MHz, CDCl3) δ
154.5, 149.8, 135.6, 131.7, 130.1, 129.0, 126.4, 124.5, 119.9, 116.5,
(R)-(Chroman-4-yloxy)tris(4-(trifluoromethyl)phenyl)silane (8e):
22.8 mg (yield = 17%), colorless oil with minor amounts of tris(4-
(trifluoromethyl)phenyl)silanol present; 1H NMR (400 MHz, CDCl3)
δ 7.71 (d, J = 8.0 Hz, 6H), 7.66 (d, J = 8.1 Hz, 6H), 7.21−7.16 (m,
1H), 6.86−6.81 (m, 2H), 6.78−6.74 (m, 1H), 4.98 (t, J = 3.9 Hz, 1H),
4.50−4.44 (m, 1H), 4.30−4.25 (m, 1H), 2.05−2.02 (m, 2H); 13C
NMR (101 MHz, CDCl3) δ 154.5, 137.6, 135.6, 132.7 (q, JCF = 32.3
Hz), 129.9, 129.8, 124.8 (q, JCF = 3.71 Hz), 123.9 (q, JCF =272.5 Hz),
122.9, 120.1, 117.1, 65.9, 61.7, 31.3; 19F NMR (377 MHz, CDCl3) δ
−63.2; [α]D25 = +23.3 (c = 0.88, CHCl3); HRMS (EI) (M+) calcd for
(C30H21F9O2Si+) 612.1161, observed 612.1171; IR (neat, cm−1) 3034,
2929, 1611, 1585, 1490, 1393, 1318, 1269, 1164, 1120, 1017, 1005,
829, 755, 705.
25
64.7, 62.3, 44.6, 34.2, 31.5, 26.9, 26.1; [α]D = +44.0 (c = 0.94,
CHCl3); HRMS (EI) (M+) calcd for (C45H54O2Si+) 654.3887,
observed 654.3884; IR (neat, cm−1) 3067, 2922, 2850, 1968, 1600,
1585, 1489, 1448, 1348, 1268, 1253, 1192, 1115, 1091, 1067, 999, 922,
816, 752, 629.
(R)-Tri([1,1′-biphenyl]-4-yl)(chroman-4-yloxy)silane (8l): 26.5 mg
(yield = 19%), white solid; mp 48−49 °C; 1H NMR (400 MHz,
CDCl3) δ 7.80 (d, J = 8.3 Hz, 6H), 7.69−7.64 (m, 12H), 7.49−7.45
(m, 8H), 7.40−7.36 (m, 3H), 7.21−7.17 (m, 1H), 7.11−7.09 (m, 1H),
6.85−6.80 (m, 2H), 5.08 (t, J = 4.2 Hz, 1H), 4.58−4.52 (m, 1H),
4.30−4.25 (m, 1H), 2.16−2.02 (m, 2H); 13C NMR (101 MHz,
CDCl3) δ 154.5, 142.8, 140.8, 136.0, 133.1, 130.1, 129.3, 128.8, 127.6,
127.2, 126.7, 124.2, 120.1, 116.7, 65.1, 62.2, 31.5; [α]D25 = +49.7 (c =
0.58, CHCl3); HRMS (EI) (M+) calcd for (C45H36O2Si+) 636.2479,
observed 636.2485; IR (neat, cm−1) 3025, 2882, 2056, 1597, 1484,
1455, 1386, 1268, 1252, 1225, 1117, 1065, 1005, 923, 830, 727, 695,
663.
(R)-(Chroman-4-yloxy)tris(4-methoxyphenyl)silane (8f): 25.1 mg
(yield = 23%), colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J
= 8.2 Hz, 6H), 7.18−7.13 (m, 1H), 7.02 (d, J = 7.7 Hz, 1H), 6.93 (d, J
= 8.6 Hz, 6H), 6.82−6.78 (m, 2H), 4.94 (t, J = 4.3 Hz, 1H), 4.48−4.42
(m, 1H), 4.22−4.17 (m, 1H), 3.83 (s, 9H), 2.02−1.92 (m, 2H); 13C
NMR (101 MHz, CDCl3) δ 161.1, 154.5, 137.1, 130.0, 129.1, 126.0,
25
124.5, 120.0, 116.6, 113.6, 64.7, 62.3, 55.0, 31.5; [α]D = +41.5 (c =
0.89, CHCl3); HRMS (EI) (M+) calcd for (C30H30O5Si+) 498.1857,
observed 498.1869; IR (neat, cm−1) 3018, 2837, 1902, 1592, 1501,
1489, 1276, 1179, 1090, 1065, 1001, 922, 810, 798, 753, 722.
(R)-(Chroman-4-yloxy)tri-p-tolylsilane (8g): 30.4 mg (yield =
ASSOCIATED CONTENT
1
■
31%), colorless oil; H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 7.8
Hz, 6H), 7.19 (d, J = 7.8 Hz, 6H), 7.15−7.11 (m, 1H), 7.03−7.01 (m,
1H), 6.80−6.75 (m, 2H), 4.93 (t, J = 4.2 Hz, 1H), 4.47−4.41 (m, 1H),
4.20−4.15 (m, 1H), 2.36 (s, 9H), 2.02−1.89 (m, 2H); 13C NMR (101
MHz, CDCl3) δ 154.5, 139.9, 135.6, 131.2, 130.0, 129.1, 128.7, 124.5,
120.0, 116.6, 64.8, 62.3, 31.5, 21.6; [α]D25 = +42.0 (c = 1.08, CHCl3);
HRMS (EI) (M+) calcd for (C30H30O2Si+) 450.2009, observed
450.2008; IR (neat, cm−1) 3066, 2921, 1917, 1599, 1584, 1488, 1454,
1393, 1225, 1111, 1065, 1003, 922, 837, 753, 716.
S
* Supporting Information
Rate data, HPLC traces, and NMR spectra (1H and 13C). This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
(R)-(Chroman-4-yloxy)tris(4-ethylphenyl)silane (8h): 39.2 mg
1
*E-mail: wiskur@mailbox.sc.edu.
(yield = 36%), colorless oil; H NMR (400 MHz, CDCl3) δ 7.59
(d, J = 8.0 Hz, 6H), 7.21 (d, J = 8.0 Hz, 6H), 7.15−7.11 (m, 1H),
7.01−6.99 (m, 1H), 6.80−6.75 (m, 2H), 4.93 (t, J = 4.0 Hz, 1H),
4.48−4.42 (m, 1H), 4.21−4.16 (m, 1H), 2.66 (q, J = 8.0 Hz, 6H),
2.04−1.90 (m, 2H), 1.24 (t, J = 8.0 Hz, 9H); 13C NMR (101 MHz,
CDCl3) δ 154.5, 146.1, 135.6, 131.5, 130.0, 129.1, 127.5, 124.5, 120.0,
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
25
116.6, 64.8, 62.3, 31.5, 28.9, 15.3; [α]D = +46.0 (c = 1.13, CHCl3);
HRMS (EI) (M+) calcd for (C33H36O2Si+) 492.2479, observed
492.2475; IR (neat, cm−1) 3067, 2964, 2873, 1916, 1601, 1585, 1489,
1455, 1398, 1268, 1226, 1112, 1091, 1003, 922, 822, 809, 753, 719.
We gratefully acknowledge support from the University of
South Carolina and the National Science Foundation CAREER
Award CHE-1055616.
2395
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396

The Journal of Organic Chemistry
Article
(34) Gustafson, J. L.; Sigman, M. S.; Miller, S. J. Org. Lett. 2010, 12,
2794.
(35) Jensen, K. H.; Sigman, M. S. J. Org. Chem. 2010, 75, 7194.
(36) Jensen, K. H.; Webb, J. D.; Sigman, M. S. J. Am. Chem. Soc.
2010, 132, 17471.
REFERENCES
■
(1) Isobe, T.; Fukuda, K.; Araki, Y.; Ishikawa, T. Chem. Commun.
2001, 243.
(2) Rendler, S.; Auer, G.; Oestreich, M. Angew. Chem., Int. Ed. 2005,
44, 7620.
(37) Li, X.; Deng, H.; Zhang, B.; Li, J. Y.; Zhang, L.; Luo, S. Z.;
(3) Zhao, Y.; Rodrigo, J.; Hoveyda, A. H.; Snapper, M. L. Nature
2006, 443, 67.
(4) Klare, H. F.; Oestreich, M. Angew. Chem., Int. Ed. 2007, 46, 9335.
(5) Zhao, Y.; Mitra, A. W.; Hoveyda, A. H.; Snapper, M. L. Angew.
Chem., Int. Ed. 2007, 46, 8471.
(6) Karatas, B.; Rendler, S.; Frohlich, R.; Oestreich, M. Org. Biomol.
Chem. 2008, 6, 1435.
(7) Rendler, S.; Plefka, O.; Karatas, B.; Auer, G.; Frohlich, R.; Muck-
Lichtenfeld, C.; Grimme, S.; Oestreich, M. Chem.Eur. J. 2008, 14,
11512.
(8) Weickgenannt, A.; Mewald, M.; Muesmann, T. W.; Oestreich, M.
Angew. Chem., Int. Ed. 2010, 49, 2223.
(9) Sheppard, C. I.; Taylor, J. L.; Wiskur, S. L. Org. Lett. 2011, 13,
3794.
(10) Sun, X.; Worthy, A. D.; Tan, K. L. Angew. Chem., Int. Ed. 2011,
Cheng, J. P. Chem.Eur. J. 2010, 16, 450.
(38) Harper, K. C.; Sigman, M. S. Science 2011, 333, 1875.
(39) Harper, K. C.; Sigman, M. S. Proc. Natl. Acad. Sci. U.S.A. 2011,
108, 2179.
(40) Wander, M.; Hausoul, P. J. C.; Sliedregt, L. A. J. M.; van Steen,
B. J.; van Koten, G.; Gebbink, R. J. M. K. Organometallics 2009, 28,
4406.
(41) Benkeser, R. A.; Riel, F. J. J. Am. Chem. Soc. 1951, 73, 3472.
(42) Arai, M. Bull. Chem. Soc. Jpn. 1964, 37, 1280.
(43) Lee, K. H. Tetrahedron 1969, 25, 4363.
(44) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
(45) Chojnowski, J.; Cypryk, M.; Michalski, J. J. Organomet. Chem.
1978, 161, C31.
(46) Bassindale, A. R.; Stout, T. J. Organomet. Chem. 1982, 238, C41.
(47) Bassindale, A. R.; Lau, J. C. Y.; Taylor, P. G. J. Organomet. Chem.
1988, 341, 213.
50, 8167.
(11) Rodrigo, J. M.; Zhao, Y.; Hoveyda, A. H.; Snapper, M. L. Org.
Lett. 2011, 13, 3778.
(12) Sun, X.; Worthy, A. D.; Tan, K. L. J. Org. Chem. 2013, 78,
(48) Chu, H. K.; Johnson, M. D.; Frye, C. L. J. Organomet. Chem.
1984, 271, 327.
(49) Chuit, C.; Corriu, R. J. P.; Reye, C.; Young, J. C. Chem. Rev.
1993, 93, 1371−1448.
10494.
(13) Manville, N.; Alite, H.; Haeffner, F.; Hoveyda, A. H.; Snapper,
M. L. Nat. Chem. 2013, 5, 768.
(14) Clark, R. W.; Deaton, T. M.; Zhang, Y.; Moore, M. I.; Wiskur, S.
L. Org. Lett. 2013, 15, 6132.
(15) Keith, J. M.; Larrow, J. F.; Jacobsen, E. N. Adv. Synth. Catal.
2001, 343, 5.
(16) Vedejs, E.; Jure, M. Angew. Chem., Int. Ed. 2005, 44, 3974.
(17) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 3rd ed.; Wiley: New York, 1999.
(18) Shiina, I.; Nakata, K.; Ono, K.; Onda, Y. S.; Itagaki, M. J. Am.
Chem. Soc. 2010, 132, 11629.
(50) Swain, C. G.; Lupton, E. C. J. Am. Chem. Soc. 1968, 90, 4328.
(51) Hansch, C.; Leo, A.; Unger, S. H.; Kim, K. H.; Nikaitan, D.;
Lien, E. J. J. Med. Chem. 1973, 16, 1207−1216.
(52) Sigman, M. S.; Miller, J. J. J. Org. Chem. 2009, 74, 7633.
(53) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. Comprehensive
Asymmetric Catalysis I−III; Springer-Verlag: New York, 1999; Vols. 1−
3.
(54) Charton, M. J. Am. Chem. Soc. 1975, 97, 1552.
(55) Charton, M. J. Am. Chem. Soc. 1975, 97, 3691.
(56) Charton, M. J. Am. Chem. Soc. 1975, 97, 3694.
(57) Hansch, C.; Leo, A. Substituent Constants for Correlation Analysis
in Chemistry and Biochemistry; John Wiley & Sons: New York, 1979.
(58) Wu, J. H.; Zhang, G. R.; Porter, N. A. Tetrahedron Lett. 1997,
38, 2067.
(19) Shiina, I.; Nakata, K.; Ono, K.; Sugimoto, M.; Sekiguchi, A.
Chem.Eur. J. 2010, 16, 167.
(20) Li, X.; Jiang, H.; Uffman, E. W.; Guo, L.; Zhang, Y.; Yang, X.;
Birman, V. B. J. Org. Chem. 2012, 77, 1722.
(59) Mantilli, L.; Gerard, D.; Torche, S.; Besnard, C.; Mazet, C.
Chem.Eur. J. 2010, 16, 12736.
(21) Nakata, K.; Gotoh, K.; Ono, K.; Futami, K.; Shiina, I. Org. Lett.
2013, 15, 1170.
(60) Huang, H.; Zong, H.; Bian, G.; Song, L. J. Org. Chem. 2012, 77,
10427.
(22) Birman, V. B.; Li, X. M. Org. Lett. 2006, 8, 1351.
(23) Kagan, H. B.; Fiaud, J. C. Top. Stereochem. 1988, 18, 249.
(24) Selectivity factor (s) = (rate of fast-reacting enantiomer)/(rate
of slow-reacting enantiomer).
(25) Conversion and selectivity factors were calculated from the ee of
the product and the ee of the recovered starting material. Selectivity
factors are an average of two runs. Conversion and er correspond to a
single run. % Conversion = ees/(ees + eep) × 100% and s = ln[(1 − C)
(1 − ees)]/ln[(1 − C)(1 + ees)], where ees = ee of recovered starting
material and eep = ee of product.
(61) Alnajjar, M.; Quigley, D.; Kuntamukkula, M.; Simmons, F.;
Freshwater, D.; Bigger, S. J. Chem. Health Safe. 2011, 18, 5.
(62) Prince, P. D.; Bearpark, M. J.; McGrady, G. S.; Steed, J. W.
Dalton Trans. 2008, 271.
(63) Beyer, C.; Bohme, U.; Pietzsch, C.; Roewer, G. J. Organomet.
Chem. 2002, 654, 187.
(64) Liew, S. K.; Al-Rafia, S. M. I.; Goettel, J. T.; Lummis, P. A.;
McDonald, S. M.; Miedema, L. J.; Ferguson, M. J.; McDonald, R.;
Rivard, E. Inorg. Chem. 2012, 51, 5471.
(26) Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic
Chemistry; University Science: Sausalito, CA, 2006.
(27) Bess, E. N.; Sigman, M. S. In Asymmetric Synthesis II: More
Methods and Applications; Christmann, M., Brase, S., Eds.; Wiley-VCH:
̈
Weinheim, Germany, 2012; p 363.
(28) Harper, K. C.; Sigman, M. S. J. Org. Chem. 2013, 78, 2813.
(29) Jacobsen, E. N.; Zhang, W.; Guler, M. L. J. Am. Chem. Soc. 1991,
113, 6703.
(30) Palucki, M.; Finney, N. S.; Pospisil, P. J.; Guler, M. L.; Ishida, T.;
Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 948.
(31) Jensen, K. H.; Sigman, M. S. Angew. Chem., Int. Ed. 2007, 46,
4748.
(32) Miller, J. J.; Sigman, M. S. Angew. Chem., Int. Ed. 2008, 47, 771.
(33) Rodriguez-Escrich, S.; Reddy, K. S.; Jimeno, C.; Colet, G.;
Rodriguez-Escrich, C.; Sola, L.; Vidal-Ferran, A.; Pericas, M. A. J. Org.
Chem. 2008, 73, 5340.
2396
dx.doi.org/10.1021/jo402569h | J. Org. Chem. 2014, 79, 2384−2396