Homoallyl-cyclopropylcarbinyl cation manifold. Trimethylsilyl versus aryl stabilization

Article abstract of DOI:10.1021/jo062668n

(Chemical Equation Presented) A series of E- and Z-1-aryl-5-trimethylsilyl- 3-buten-1-yl trifluoroacetates were solvolyzed in CD₃CO₂D, and rates of reaction as well as products derived from these reactions were determined. Hammett pl

Full text of DOI:10.1021/jo062668n

Homoallyl-Cyclopropylcarbinyl Cation Manifold. Trimethylsilyl
versus Aryl Stabilization
Xavier Creary,* Benjamin D. O’Donnell, and Marie Vervaeke
Department of Chemistry and Biochemistry, UniVersity of Notre Dame, Notre Dame, Indiana 46556
creary.1@nd.edu
ReceiVed December 28, 2006
A series of E- and Z-1-aryl-5-trimethylsilyl-3-buten-1-yl trifluoroacetates were solvolyzed in CD3CO2D,
and rates of reaction as well as products derived from these reactions were determined. Hammett plots
showed a break, which was indicative of a mechanistic change from a kC process when the most electron-
donating substituents were attached to the aryl group to a k∆ process involving formation of cyclized
â-silyl carbocation intermediates for electron-withdrawing groups. In the case of p-CH3O substitution (a
kC extreme), the cationic intermediate captures solvent (95%) or loses a proton (5%). In the case of
m-CF3 substitution (a k∆ extreme), the â-silyl cation intermediate desilylates to give vinylcyclopropane
products. Substituents with intermediate electronic properties give more complex product mixtures.
Solvolysis of pure Z-trifluoroacetate (p-CH3) gives small amounts of E-trifluoroacetate (p-CH3) along
with the E-substitution product. This isomerization suggests that the cyclized â-silyl cation can isomerize
and then reopen to a classical aryl-stabilized cation. By way of contrast, B3LYP/6-31G* computational
studies show only cyclized â-silyl cations as energy minima. Open kC cations are higher-energy
nonminimum energy structures.
Introduction
vinylcyclopropanes 6 from 5.3 It was suggested that “activation”
of 5 leads to neighboring double bond participation and
subsequent formation of the â-silyl-stabilized carbocation 8.
Subsequent loss of the trimethylsilyl group ultimately leads
to the vinylcyclopropanes 6. Use of enantiomerically pure
alcohols 5 led, in some cases, to enantiomerically pure cyclo-
propanes 6,3a whereas in other cases, there was loss of
enantioselectivity.4
Stabilization of carbocations 1 by adjacent silicon is quite
dramatic, and this phenomenon has been extensively studied
quantitatively by Lambert.1 This stabilization by â-silyl groups
is due to a favorable interaction between the cation vacant
p-orbital and the adjacent C-Si σ-bond. We have shown that a
similar interaction occurs in carbenes 3, and this interaction leads
to facile rearrangement of carbenes 3 to alkenes 4 via silicon
migration.2 Taylor has recently developed a synthesis of
In light of our interest in carbocation chemistry,5 the
phenomenon of neighboring group participation,6 and the
(1) (a) Lambert, J. B.; Wang, G.-t.; Finzel, R. B.; Teramura, D. H. J.
Am. Chem. Soc. 1987, 109, 7838. (b) Lambert, J. B.; Chelius, E. C. J. Am.
Chem. Soc. 1990, 112, 8120. (c) Lambert, J. B. Tetrahedron 1990, 46, 2677.
(d) Lambert, J. B.; Liu, X. J. Organomet. Chem. 1996, 521, 203. (e)
Lambert, J. B.; Zhao, Y.; Emblidge, R. W.; Salvador, L. A.; Liu, X.; So, J.
H.; Chelius, E. C. Acc. Chem. Res. 1999, 32, 183.
(2) (a) Creary, X.; Wang, Y.-X. J. Org. Chem. 1994, 59, 1604-1605.
(b) Creary, X.; Jiang, Z.; Butchko, M.; McLean, K. Tetrahedron Lett. 1995,
37, 579. (c) Creary, X.; Butchko, M. A. J. Org. Chem. 2001, 66, 1115. (d)
Creary, X.; Butchko, M. A. J. Org. Chem. 2002, 67, 112.
(3) (a) Taylor, R.; Engelhardt, F. C.; Schmitt, M. J.; Yuan, H. J. Am.
Chem. Soc. 2001, 123, 2964. (b) Taylor, R.; Schmitt, M. J.; Yuan, H. Org.
Lett. 2000, 2, 601. (c) Taylor, R.; Engelhardt, F. C.; Yuan, H. Org. Lett.
1999, 1, 1257. (d) Taylor, R. E.; Ameriks, M. K.; LaMarche, M. J.
Tetrahedron Lett. 1997, 38, 2057.
(4) Melancon, B. J.; Perl, N. R.; Taylor, R. E. Org. Lett. 2007, 9, 1425-
1428.
(5) Creary, X. Chem. ReV. 1991, 91, 1625.
(6) (a) Creary, X.; Mehrsheikh-Mohammadi, M. E. J. Org. Chem. 1986,
51, 7. (b) Creary, X.; Aldridge, T. J. Org. Chem. 1988, 53, 3888.
10.1021/jo062668n CCC: $37.00 © 2007 American Chemical Society
Published on Web 04/04/2007
3360
J. Org. Chem. 2007, 72, 3360-3368

Homoallyl-Cyclopropylcarbinyl Cation Manifold
SCHEME 1
effect of silicon on adjacent electron-deficient reactive inter-
mediates,2 we have turned our attention to the reactions of a
series of cis-trifluoroacetates 9 and trans-trifluoroacetates 10.
It was our intent to determine, by kinetic studies, the mechanistic
details of reactions of these substrates under solvolytic condi-
tions. When loss of enantioselectivity occurs in formation of 6,
what are the reasons? Is there a mechanistic change from the
k∆ to the kC process, and if so, where does this change occur?
Reported here are the results of kinetic studies on 9 and 10 as
well as computational studies on related â-silyl-substituted
carbocations.
not linear. These breaks in the Hammett plots for solvolyses of
substrates 9 and 10 are indicative of changes in the mechanism
as substituents change from electron-withdrawing to electron-
donating.7 The slope of the Hammett plot for cis-trifluoroacetates
Results and Discussion
Synthetic Aspects. The pure cis-trifluoroacetates 9 were
prepared using the methodology in Scheme 1 developed by the
Taylor group.3a-c Silylation of the homoallylic alcohols 12 with
allyldimethylsilyl chloride followed by intramolecular olefin
metathesis gave silyl ethers 14 which were cleaved to the pure
cis-alcohols 15. The trans-trifluoroacetates 10 were prepared
using a cross-metathesis reaction of 12 with allyltrimethylsilane.3a
The inseparable mixture of alcohols 16 was converted to a
mixture of trifluoroacetates 10 and 9 (E/Z ratio ) 3). Fortu-
nately, the 1H NMR signals due to the trimethylsilyl groups of
10 and 9 are cleanly separated. This permits facile determination
of solvolysis rates of the trans-trifluoroacetates 10 using this
mixture. For comparison purposes, the mesylates 17, 18, and
21 were also prepared and studied along with the substrates
19, 20, and 22, which contain double bonds not activated by
trimethylsilyl groups.
9 in Figure 1 is -6.4 for the most electron-donating substituents,
and this is indicative of a relatively high demand for stabilization
of the cationic intermediate by the aryl substituent, i.e., a kC
mechanism. On the other hand, the reduced slope of -2.5 for
the more electron-withdrawing substituents is indicative of a
different cationic intermediate with less demand for aryl group
stabilization, i.e., a k∆ mechanism. Analogous behavior is
observed for the trans-isomers 10 in Figure 2.
Silylated/Unsilylated Rate Ratio. A comparison of the
acetolysis rates of 9 and 10 with that of the homoallylic
trifluoroacetates 19 is informative. The silylated substrates 9
and 10 are all more reactive than the unsilylated analogues 19.
The p-OCH3 derivatives of 9 and 10 are twice as reactive as 19
(p-OCH3), and this indicates that the double bond in 19 (p-
OCH3) is slightly more inductively electron-withdrawing than
are the nonparticipating double bonds in 9 (p-OCH3) and 10
(p-OCH3). However, there is a smooth increase in the 9/19 and
10/19 rate ratios as substituents become more electron-
Kinetic Studies. Rates of reaction of trifluoroacetrates and
mesylates were measured in CD3CO2D containing 1.5 equiv of
2,6-lutidine and were monitored by 600 MHz 1H NMR
spectroscopy. Rate data are summarized in Table 1, and the
corresponding Hammett plots for the data are shown in Figures
1 and 2. Immediately apparent is the fact that these plots are
(7) Gassman, P. G.; Fentiman, A. F. J. Am. Chem. Soc. 1970, 92, 2549.
J. Org. Chem, Vol. 72, No. 9, 2007 3361

Creary et al.
TABLE 3. Product Ratios from Solvolyses of 9 in CD3CO2D
TABLE 1. Solvolysis Rate Constants for Substrates in CD3CO2D
a
substrate
9 (m-CF3)
temp (°C)
k (s-1
)
substrate
24
25
27
28
29
80.0
60.0
25.0b
80.0
60.0
25.0b
65.0
45.0
25.0b
60.0
40.0
25.0b
25.0
25.0
25.0
25.0
80.0
60.0
25.0b
80.0
60.0
25.0b
65.0
45.0
25.0b
60.0
40.0
25.0b
25.0
25.0
25.0
25.0
25.0
25.0
25.0
25.0
25.0b
25.0b
25.0b
25.0
25.0
25.0
1.81 × 10-5
2.25 × 10-6
3.0 × 10-8
3.64 × 10-5
4.52 × 10-6
6.1 × 10-8
3.15 × 10-5
3.22 × 10-6
2.4 × 10-7
3.29 × 10-5
3.34 × 10-6
4.9 × 10-7
2.96 × 10-6
4.61 × 10-6
5.92 × 10-5
7.77 × 10-4
3.60 × 10-5
4.17 × 10-6
4.8 × 10-8
7.50 × 10-5
9.01 × 10-6
1.1 × 10-7
6.02 × 10-5
6.23 × 10-6
4.8 × 10-7
7.21 × 10-5
7.38 × 10-6
1.1 × 10-6
6.82 × 10-6
1.12 × 10-5
7.58 × 10-5
7.77 × 10-4
3.27 × 10-5
5.47 × 10-5
3.88 × 10-4
2.81 × 10-5
7.8 × 10-7
6.0 × 10-9
5.1 × 10-8
2.48 × 10-3
4.75 × 10-3
5.73 × 10-6
9 (m-CF3)
9 (m-F)
9 (p-Cl)
95
95
91
86
52
44
6
5
5
6
5
2
2
0
0
0
0
3
0
0
0
1
5
6
3
5
0
0
0
1
5
5
2
0
9 (m-F)
9 (p-Cl)
9 (p-H)
9 (p-H)
7
9 (p-CH3)
9 (3,4-di-CH3)
9 (p-SCH3)
9 (p-OCH3)
36
43
89
95
0
SCHEME 2
9 (p-CH3)
9 (3,4-di-CH3)
9 (p-SCH3)
9 (p-OCH3)
10 (m-CF3)
10 (m-F)
10 (p-Cl)
10 (p-H)
10 (p-CH3)
10 (3,4-di-CH3)
10 (p-SCH3)
10 (p-OCH3)
17
18
19 (p-OCH3)
19 (p-SCH3)
19 (3,4-di-CH3)
19 (p-H)
20
cis-21
trans-21
22
studied. They are 433 and 830 times faster reacting, respectively,
than the mesylate 22 that has no silyl group. Anchimeric
assistance in 21 is becoming much more pronounced due to
increased demand for cation stabilization by the participating
double bonds in 21. Finally, if one replaces the cation stabilizing
aryl group with a simple methyl group, as in mesylates 17 and
18, the silylated/unsilylated ratio reaches values of 644 and
1077.9
a
b
Maximum standard deviation in duplicate runs was (2%. Extrapo-
lated from data at higher temperatures.
TABLE 2. Silylated/Unsilylated Rate Ratios in Solvolyses in
CD3CO2D at 25 °C
substituent
9/19
10/19
p-OCH3
p-SCH3
3,4-di-CH3
p-H
2.0
2.1
5.9
2.0
2.7
14.3
183
83
m-CF3
433a
830b
a
This is the cis-21/22 mesylate ratio. b This is the trans-21/22 mesylate
ratio.
withdrawing (Table 2). This is attributed to the onset of
neighboring double bond participation in 9 and 10, which leads
to increasing anchimeric assistance as substituents become more
electron-withdrawing.8 In the case of the strongly electron-
withdrawing m-CF3 substituent, the silylated/unsilylated ratio
was determined for the corresponding mesylates because the
trifluoroacetates are quite unreactive. Although both E- and
Z-mesylates 21 are highly reactive substrates in CD3CO2D (half-
lives of 146 and 280 s, respectively), they can be prepared and
Product Studies. The products derived from solvolyses of 9
in CD3CO2D are shown in Table 3, and they are quite dependent
on the substituent. The electron-withdrawing m-CF3 and m-F
substituents lead to exclusively cyclized products 24 and 25,
(9) Note that the acetolysis rate of unsilylated mesylate 20 is somewhat
assisted by the homoallylic double bond, as revealed by the formation of
small amounts of cyclopropane products from 20.
(8) Brown, H. C. The Nonclassical Ion Problem; Plenum Press: New
York, 1977.
3362 J. Org. Chem., Vol. 72, No. 9, 2007

Homoallyl-Cyclopropylcarbinyl Cation Manifold
FIGURE 1. Plot of log k for reaction of 9 at 25 °C in CD3CO2D vs σ+.
FIGURE 2. Plot of log k for reaction of 10 at 25 °C in CD3CO2D vs σ+.
and this is indicative of solvolysis proceeding completely via
the k∆ pathway (cation 23). The aliphatic analogues 17 and 18
are also k∆ substrates which give the completely cyclized
products trans- and cis-1-methyl-2-vinylcyclopropane. With p-Cl
and p-H substituents, one begins to see small amounts of
products 27 and 28 that are not cyclized. These products are
derived from the capture of acetic acid or proton loss from an
open carbocation 26 (the kC process; Scheme 2). They assume
increasing importance with p-CH3, 3,4-di-CH3, and p-SCH3
substitution. In the case of 9 (p-OCH3), there is no cyclized
vinylcyclopropane product; i.e., the k∆ process is bypassed in
favor of the kC solvolysis route.
J. Org. Chem, Vol. 72, No. 9, 2007 3363

Creary et al.
1
FIGURE 3. Evolving upfield region of H NMR spectra during solvolysis of 9 (p-CH3) in CD3CO2D showing the developing TMS groups of 10
(p-CH3) and 29 (p-CH3).
FIGURE 4. 1H NMR spectra of solvolysis products from cis-9 (p-SCH3) in CD3CO2D (bottom) and from a 24:76 mixture of cis-9 (p-SCH3) and
trans-9 (p-SCH3) (top).
Careful examination of the products formed when pure cis-
trifluoroacetates 9 (p-H, p-CH3, 3,4-di-CH3, and p-SCH3) react
in CD3CO2D shows the presence of small amounts (1-5%) of
trans-acetates 29. What is the origin of these isomerized
CH3) at -0.076 ppm, which is slightly more reactive than cis-9
(p-CH3). It is suggested that the source of trans-acetate 29
(which appears at -0.074 ppm) is isomerization of cis-9. The
mechanism of this isomerization is suggested in Scheme 3. The
k∆ process leads to the cyclized cation 23. In this cation, the
large â-silicon stabilization results in a small barrier to rotation
about the C3-C4 bond and isomerization to 30 can occur.
Competing with loss of trimethylsilyl from 30 is reopening of
cation 30 to the aryl-stabilized cation 31, which now has a trans
double bond configuration. Internal return of the trifluoroacetate
1
products? Careful monitoring of these reactions by H NMR
offers an explanation. Figure 3 shows a portion of the evolving
1
upfield region of the H NMR spectrum during solvolysis of
cis-9 (p-CH3). Note that there is no trace of trans-10 (p-CH3)
at the beginning of the reaction. However, as the reaction
proceeds, there is a buildup of a small amount of trans-10 (p-
3364 J. Org. Chem., Vol. 72, No. 9, 2007

Homoallyl-Cyclopropylcarbinyl Cation Manifold
SCHEME 3
ion accounts for the transient appearance of trans-10 (p-CH3),
and solvent capture leads to the trans-acetate 29.
closure to give racemic 23 or internal return to give racemic
starting material are other processes that would lead to loss of
optical purity in 24.
Precise ratios of products derived from solvolyses of trans-
trifluoroacetates 10 are somewhat more difficult to measure
because samples of 10 used for study all contained ap-
proximately 25% of the cis-trifluoroacetates 9. However, the
trans-trifluoroacetates 10 gave slightly more cyclized vinylcy-
clopropanes 24 and 25 than the cis-trifluoroacetates 9, which
is consistent with the slightly greater rate enhancements due to
the competing k∆ processes. For example, Figure 4 shows a
comparison of the vinylcyclopropanes formed from pure cis-9
(p-SCH3) (bottom; 6%) with the vinylcyclopropanes formed
from a 24:76 mixture of 9/10 (top; 26%). This means that 32%
vinylcyclopropanes would be produced from “pure” trans-10
(p-SCH3). The kinetic data, which show that trans-10 (p-SCH3)
reacts 2.7 times faster than 19 (p-SCH3), are consistent with a
small k∆ component in the rate of trans-10 (p-SCH3).
Computational Studies. B3LYP/6-31G* computational stud-
ies10 have been carried out to shed light on the cationic
intermediates involved in these studies. These calculations show
two minimum-energy structures (32 and 33) that could be
potentially derived from cis-trifluoroacetate 9 and trans-
trifluoroacetate 10. These cations would produce the major
solvolysis product, trans-vinylcyclopropane 24. The cation 33
(derived from 10) lies 1.4 kcal/mol lower in energy than the
cation 32 (derived from 9). This energy difference is in line
with the slightly faster solvolyses rates of trans-isomers 10
relative to cis-isomers 9 when the k∆ process dominates. Both
cations 32 and 33 show elongated cyclopropane bonds (1.837
and 1.787 Å, respectively). These cations are best described as
partially closed homoallyic cations, where cyclopropane bond
formation is more extensive than in the cation 36 where there
A question arises as to the ability of closed cation 23 and
open cation 26 to interconvert. In view of the suggestion that
closed cation 30 can open to 31, it is a likely possibility that 23
can open to 26. This suggestion is relevant to the observation
of Taylor,4 who observed some loss of enantiomeric purity when
optically active 5 (R ) C6H5, p-CH3C6H4) was cyclized to the
vinylcyclopropanes 24 via in situ conversion to the mesylate.
A clean k∆ process should lead to complete inversion at the
ionization center. However, competing opening of 23 (Ar )
C6H5, p-CH3C6H4) to achiral 26 and reclosure could account
for partial loss of enantiomeric purity in the product 24.
Competing kC ionization of 9 to give achiral 26 followed by
(10) Frisch, M. J. et al. Gaussian 03, revision C.01; Gaussian, Inc.:
Wallingford, CT, 2004.
J. Org. Chem, Vol. 72, No. 9, 2007 3365

Creary et al.
the computational studies may account for the discrepancy with
solution results.
Conclusions
The nonlinear Hammett plot in the solvolyses of trifluoro-
acetates 9 and 10 in CD3CO2D is indicative of a change in
mechanism as substituents vary from electron-donating to
electron-withdrawing. Thus, p-OCH3 substitution leads to a kC
mechanism involving unassisted formation of an open carboca-
tion 26 that undergoes solvent capture or proton loss. At the
other mechanistic extreme, m-CF3 substitution results in a k∆
process as the silyl-substituted double bond assists in the
ionization process to form a closed â-silyl carbocation 23. This
â-silyl cation suffers desilylation to give vinylcyclopropanes.
This relatively simple mechanistic picture is complicated by the
apparent interconversion of open and closed cations 26 and 23,
as evidenced by the formation of small amounts of trans-10
and trans-29 during the solvolysis of pure cis-9 with certain
substituents. In agreement with rate data, computational studies
at the B3LYP/6-31G* level show that the closed cation 33
derived from trans double bond participation in 10 (Ar ) C6H5)
is 1.4 kcal/mol more stable than cation 32 derived from cis-9
(Ar ) C6H5). Open cations 26 are not energy minima at the
B3LYP/6-31G* computational level even when Ar ) p-CH3-
OC6H4. This computational finding is in conflict with conclu-
sions based on the nonlinear Hammett plots that implicate
discrete open as well as closed cations from 9 and 10 depending
on aryl substitution.
is no silicon to stabilize the cationic intermediate. However,
cyclopropane bond formation, although more advanced than in
cation 36, is still less than complete. â-Silyl stabilization of the
B3YLP/6-31G* cations 32 and 33 is insufficient to completely
offset phenyl stabilization. As expected on the basis of steric
factors, the related cations 34 and 35 that would lead to cis-
vinylcyclopropanes 25 lie 7.0 and 2.3 kcal/mol higher in energy
than 33, respectively.
It is interesting to note that no minimum-energy structures
can be found that would correspond to the open cation 26. Even
in the case of the p-OCH3-substituted cation 37, there is still
significant cyclopropane bond formation (C1-C3 bond ) 2.194
Å) as well as silyl stabilization of this cation. Thus all cations
have varying degrees of both aryl and trimethylsilyl stabilization.
If one introduces artificial constraints into the calculation to
prevent cyclization (by fixing the C+-C2-C3-C4 dihedral
angle in 38 at 180°), then the resultant p-OCH3-stabilized
benzylic cation 38 (not an energy minimum) is 11.2 kcal/mol
less stable than the closed form 37. Although this computational
picture sheds some light on the mode of cation stabilization,
open structures corresponding to 26 are all higher in energy at
the B3LYP/6-31G* level and do not correspond to energy
minima. However, we believe that distinct open and closed ions
that can interconvert are the better mechanistic picture of what
happens in solution. The Hammett plots in Figures 1 and 2
support this view of distinct open cations 26 and closed cations
23, as does the formation of small amounts of trans-acetates
29 from pure cis-trifluoroacetates 9. The gas-phase nature of
Experimental Section
Preparation of Silyl Ethers 13. General Procedure. A solution
of the appropriate homoallylic alcohol 12 (5 mmol) (prepared by
reaction of allylmagnesium chloride with the corresponding ben-
zaldehyde 11) in CH2Cl2 containing 10 mmol of Et3N and 5 mmol
of imidazole was cooled to -10 °C, and 6 mmol of allyldimeth-
ylsilyl chloride in CH2Cl2 was added dropwise. The mixture was
allowed to warm to room temperature. and after 1 h, the mixture
was transferred to a separatory funnel with 25 mL of ether. The
mixture was washed with cold water and cold dilute HCl solution.
The organic phase was dried over a mixture of Na2SO4 and MgSO4
and filtered, and the solvent was removed using a rotary evaporator.
The residue was distilled to give the silyl ethers 13. The following
procedure is representative.
3366 J. Org. Chem., Vol. 72, No. 9, 2007

Homoallyl-Cyclopropylcarbinyl Cation Manifold
Reaction of 688 mg of alcohol 12 (Ar ) C6H5) with 940 mg of
Et3N and 316 mg of imidazole in 8 mL of CH2Cl2 with 719 mg of
allyldimethylsilyl chloride gave 834 mg of 13 (Ar ) C6H5) (73%)
(bp 61-62 °C) (0.1 mm). 1H NMR of 13 (Ar ) C6H5) (CDCl3) δ
7.34-7.22 (m, 5 H), 5.76 (m, 1 H), 5.71 (m, 1 H), 5.06-5.00 (m,
2 H), 4.83 (m, 1 H), 4.81 (m, 1 H), 4.69 (d of d, J ) 7.6, 5.3 Hz,
1 H), 2.48 (m, 1 H), 2.40 (m, 1 H), 1.55 (t, J ) 1.2 Hz, 1 H), 1.54
(t, J ) 1.2 Hz, 1 H), 0.45 (s, 3 H), 0.43 (s, 3 H). 13C NMR of 13
(Ar ) C6H5) (CDCl3) δ 144.7, 135.2, 128.1, 127.2, 125.9, 117.0,
113.6, 75.1, 45.1, 24.9, -1.9, -2.0. Exact mass (CI) calcd for
C15H23OSi 247.1518, found 247.1488.
added, and the mixture was rapidly transferred to a separatory funnel
using ether. The ether extract was washed with cold dilute HCl
solution, NaHCO3 solution, and saturated NaCl solution and and
dried over MgSO4. After filtration, the ether solvent was removed
using a rotary evaporator to give the crude trifluoroacetates that
were used without further purification. These trifluoroacetates 9
and 19 were all stored in ether at -20 °C. The following procedures
are representative.
Reaction of 82 mg of alcohol 15 (Ar ) p-CH3C6H4) and 55 mg
of 2,6-lutidine in 2 mL of ether with 95 mg of trifluoroacetic
anhydride gave 108 mg of trifluoroacetate 9 (Ar ) p-CH3C6H4)
(95%) as an oil. 1H NMR of 9 (Ar ) p-CH3C6H4) (CDCl3) δ 7.26
(d, J ) 8.0 Hz, 2 H), 7.19 (d, J ) 8.0 Hz, 2 H), 5.83 (d of d, J )
8.1, 6.3 Hz, 1 H), 5.55 (m, 1 H), 5.14 (m, 1 H), 2.75 (m, 1 H),
2.56 (m, 1 H), 2.35 (s, 3 H), 1.46 (m, 2 H), 0.0 (s, 9 H). 13C NMR
of 9 (Ar ) p-CH3C6H4) (CDCl3) δ 156.8 (q, J ) 286 Hz), 138.8,
135.0, 130.0, 129.4, 126.7, 120.1, 114.6 (q, J ) 42 Hz), 80.5, 33.6,
21.2, 18.9, -1.8. Exact mass (FAB) calcd for C17H23F3O2Si
344.1419, found 344.1424.
Preparation of Cyclic Silyl Ethers 14. General Procedure. A
solution of approximately 3 mmol of silyl ether 13 in 30 mL of
freshly distilled CH2Cl2 was stirred at room temperature as 20-30
mg of Grubbs second-generation catalyst, tricyclohexylphosphine-
(1,3-bismesityl-4,5-dihydroimidazol-2-ylidene)(benzylidine) ruthe-
nium dichloride, was added in one portion. The mixture was either
stirred at room temperature or refluxed. The progress of the reaction
1
was monitored by removal of small portions and analysis by H
NMR. An additional 25 mg of catalyst was added if the reaction
ceased to progress. On completion of the reaction, the CH2Cl2 was
removed using a rotary evaporator and the residue was taken up
into hexanes and filtered through a small amount of silica gel to
remove the insoluble catalyst. Solvent removal gave the crude silyl
ethers 14 that were used without further purification. The following
procedure is representative.
Reaction of 121 mg of alcohol 12 (Ar ) C6H5) and 142 mg of
2,6-lutidine in 3 mL of ether with 240 mg of trifluoroacetic
anhydride gave 180 mg of trifluoroacetate 19 (Ar ) C6H5) (90%)
as an oil. 1H NMR of 19 (Ar ) C6H5) (CDCl3) δ 7.42-7.33 (m, 5
H), 5.93 (d of d, J ) 8.1, 5.6 Hz, 1 H), 5.69 (m, 1 H), 5.18-5.11
(m, 2 H), 2.77 (m, 1 H), 2.67 (m, 1 H). 13C NMR of 19 (Ar )
C6H5) (CDCl3) δ 156.8 (q, J ) 286 Hz), 137.6, 131.9, 129.0, 128.8,
126.5, 119.4, 114.6 (q, J ) 42 Hz), 79.6, 40.4. Exact mass (FAB)
calcd for C12H11F3O2 244.0711, found 244.0711.
Preparation of Alcohols 16. These substrates were prepared
using the olefin cross-metathesis procedure of Taylor.3a Alcohols
16 were formed as a 3:1 mixture of E/Z stereoisomers, which were
converted directly to the corresponding trifluoroacetate mixture 9
and 10. The following procedure is representative.
Reaction of 649 mg of silyl ether 13 (Ar ) C6H5) in 28 mL of
CH2Cl2 with 20 mg of Grubbs second-generation catalyst for 5 h
at room temperature followed by the addition of 30 mg of fresh
catalyst and reaction for 3 h at room temperature gave, after filtering
through 2 g of silica gel, 424 mg of 14 (Ar ) C6H5) (74%) as a
1
clear oil. H NMR of 14 (Ar ) C6H5) (CDCl3) δ 7.38 (m, 2 H),
7.34 (m, 2 H), 7.24 (m, 1 H), 5.93 (m, 1 H), 5.69 (m, 1 H), 5.02
(d of d, J ) 9.7, 1.6 Hz, 1 H), 2.67 (m, 1 H), 2.38 (d of d of d, J
) 15.4, 7.7, 1.8 Hz, 1 H), 1,87 (d of d of d, J ) 15.0, 7.7, 1.8 Hz,
1 H), 1.54 (d of d, J ) 15.0, 7.7 Hz, 1 H), 0.23 (s, 3 H), 0.22 (s,
3 H). 13C NMR of 14 (Ar ) C6H5) (CDCl3) δ 145.5, 128.9, 128.2,
126.9, 126.5, 125.3, 74.8, 39.9, 18.5, -0.1, -2.0. Exact mass (FAB)
calcd for C13H18OSi 218.1127, found 218.1140.
A solution of 480 mg of 4-penten-2-ol, 2.55 g of allyltrimeth-
ylsilane, and 38 mg of catalyst in 40 mL of CH2Cl2 was refluxed
for 1 h. After solvent removal, chromatography on 6 g of silica gel
gave 602 mg of a 3:1 mixture of E- and Z-1-trimethylsilyl-5-
hydroxy-hex-2-ene.12
Preparation of Mesylates 17, 18, and 20-22. General Pro-
cedure. A solution of approximately 5 mmol of the appropriate
alcohol in 3-4 mL of CH2Cl2 containing 1.3 equiv of CH3SO2Cl
was cooled to -50 °C, and 1.5 equiv of Et3N was added dropwise.
The mixture was allowed to warm to 10 °C and after 5 min was
re-cooled to 0 °C. Cold water was then added, and the mixture
was rapidly transferred to a separatory funnel using ether. The ether
extract was rapidly washed with cold dilute HCl solution, NaHCO3
solution, and saturated NaCl solution and dried over MgSO4. After
filtration, the solvents were removed using a rotary evaporator to
give the crude mesylates that were used without further purification.
These mesylates were all stored in ether at -20 °C. The following
procedures are representative.
Preparation of Alcohols 15. General Procedure. A solution
of approximately 1 mmol of silyl ether 14 in 5-8 mL of anhydrous
tetrahydrofuran was cooled to -78 °C, and 1.5 equiv of 1.6 M
methyllithium in ether was added dropwise. The solution was
allowed to warm to room temperature, and stirring was continued
for 1 h. The solution was re-cooled to -30 °C, and water was added.
The mixture was transferred to a separatory funnel using ether, and
the organic extract was separated, washed with water and saturated
NaCl solution, and dried over MgSO4. The solvent was removed
using a rotary evaporator, and the residue was chromatographed
on silica gel. The product 15 was eluted with 10% ether in hexanes.
The following procedure is representative.
Reaction of 344 mg of silyl ether 14 (Ar ) C6H5) in 8 mL of
THF with 1.4 mL of 1.6 M methyllithium in ether gave, after
chromatography on 5.5 g of silica gel, 310 mg of alcohol 15 (Ar
) C6H5) (84%).11 1H NMR of 15 (Ar ) C6H5) (CDCl3) 7.40-7.34
(m, 4 H), 7.28 (m, 1 H), 5.62 (m, 1 H), 5.31 (m, 1 H), 4.70 (d of
d, J ) 8.2, 5.2 Hz, 1 H), 2.53 (m, 1 H), 2.43 (m, 1 H), 2.07 (br s,
1 H), 1.55 (m, 1 H), 1.49 (m, 1 H), 0.01 (s, 9 H). 13C NMR of 15
(Ar ) C6H5) (CDCl3) δ 144.3, 129.5, 128.4, 127.5, 125.8, 122.3,
74.0, 37.1, 18.8, -1.8.
Preparation of Trifluoroacetates 9 and 19. General Proce-
dure. A solution of approximately 0.3 mmol of the appropriate
alcohol 15 or 12 in 2 mL of ether containing 1.5 equiv of 2,6-
lutidine was cooled to -10 °C, and 1.3 equiv of trifluoroacetic
anhydride was added dropwise. The mixture was allowed to warm
to 10 °C and after 5 min was re-cooled to -10 °C. Water was then
Reaction of 110 mg of a 3:1 mixture of E- and Z-1-trimethylsilyl-
5-hydroxy-hex-2-ene and 95 mg of CH3SO2Cl in 3 mL of CH2Cl2
with 97 mg of Et3N gave 146 mg (92% yield) of a mixture of
mesylates 17 and 18. These mesylates decomposed on prolonged
standing at room temperature and were therefore stored in ether
solution at -20 °C.
Reaction of 99 mg of 4-penten-2-ol and 144 mg of CH3SO2Cl
in 3 mL of CH2Cl2 with 178 mg of Et3N gave 165 mg (87% yield)
of mesylate 20.13 1H NMR of 20 (CDCl3) δ 5.79 (m, 1 H), 5.18
(m, 1 H), 5.16 (m, 1 H), 4.83 (sextet, J ) 6.3 Hz, 1 H), 3.00 (s, 3
H), 2.47 (m, 1 H), 2.41 (m, 1 H), 1.43 (d, J ) 6.3 Hz, 3 H). 13C
NMR of 20 (CDCl3) δ 132.4, 119.1, 79.1, 40.9, 38.7, 20.8.
(12) (a) Nishiyama, H.; Narimatsu, S.; Itoh, K. Tetrahedron Lett. 1981,
22, 5289. (b) Mohr, P.; Tamm, C. Tetrahedron Lett. 1987, 28, 391. (c)
Mohr, P. Tetrahedron Lett. 1992, 33, 2455.
(11) Degl’Innocenti, A.; Mordini, A.; Pagliai, L.; Ricci, A. Synlett 1991,
3, 155.
(13) Bloodworth, A. J.; Curtis, R. J.; Spencer, M. D.; Tallant, N. A.
Tetrahedron 1993, 49, 2729.
J. Org. Chem, Vol. 72, No. 9, 2007 3367

Creary et al.
Reaction of 19 mg of alcohol 16 (Ar ) m-CF3C6H4) and 11 mg
of CH3SO2Cl in 1.5 mL of CH2Cl2 with 10 mg of Et3N gave a
mixture of mesylates 21. Mesylates 21 are highly reactive sub-
stances that decompose at room temperature or on standing in
CDCl3 at room temperature. NMR spectra in CDCl3 were recorded
at 5 °C. Samples of 21 were stored in ether at -20 °C, and solvents
were rapidly removed when preparing samples for kinetic studies.
Reaction of 133 mg of alcohol 12 (Ar ) m-CF3C6H4) and 97
mg of CH3SO2Cl in 3 mL of CH2Cl2 with 103 mg of Et3N gave
data illustrating this method are given as Supporting Information.
In the case of trifluoroacetates 19, the rate of disappearance of the
doublet of doublets at δ 5.9-6.0 was monitored. For mesylates 17
and 18, the rates of disappearance of the CH3SO3R singlets at δ
3.025 and 3.017 were monitored. For mesylates 20 and 22, the rates
of disappearance of the CH3SO3R singlets at δ 3.022 and 2.914
were monitored. For mesylates 21, the rates of disappearance of
the CH3SO3R singlets at δ 2.921 (Z-isomer) and 2.886 (E-isomer)
were monitored. First-order rate constants for the disappearance
of substrates were calculated by standard least-squares procedures.
Correlation coefficients were all greater than 0.9999. The maximum
standard deviation in duplicate runs was (2%.
1
164 mg (91% yield) of mesylate 22. H NMR of 22 (CDCl3) δ
7.65-7.61 (m, 2 H), 7.58 (d, J ) 8 Hz, 1 H), 7.54 (t, J ) 8 Hz, 1
H), 5.71 (m, 1 H), 5.62 (d of d, J ) 7.7, 6.0 Hz, 1 H), 5.16 (m, 1
H), 5.14 (m, 1 H), 2.81 (s, 3 H), 2.80 (m, 1 H), 2.66 (m, 1 H). 13
C
Solvolyses of Trifluoroacetates 9 in CD3CO2D. Product
Studies. A solution of the appropriate trifluoroacetate 9 in CD3-
CO2D containing 1.5 equiv of 2,6-lutidine was kept at the
appropriate temperature for 10 half-lives. The mixture was then
NMR of 22 (CDCl3) δ 139.3, 131.4, 131.3 (q, J ) 32 Hz), 130.1,
129.5, 125.8 (q, J ) 3.7 Hz), 123.8 (q, J ) 272 Hz), 123.4 (q, J )
3.8 Hz), 119.9, 82.3, 41.4, 39.0. Exact mass (FAB) calcd for
C12H13F3O3S 294.0537s, found 294.0534.
1
analyzed by 600 MHz H NMR for the relative amounts of each
Solvolyses of Trifluoroacetates and Mesylates in CD3CO2D.
Kinetic Studies. Rate constants reported in Table 1 were all
determined using 500 or 600 MHz 1H NMR spectroscopy. A
solution was prepared by dissolving approximately 5 mg of the
appropriate substrate in 400 mg of CD3CO2D containing ap-
proximately 1.5 equiv of 2,6-lutidine. (The CD3CO2D is hygro-
scopic, and care was taken to keep the solvent dry.) A sample was
sealed in an NMR tube. For runs at 25 °C, the tube was placed in
the probe of an NMR set at 25.0 °C. At appropriate time intervals,
the tube was analyzed by 1H NMR, and relative areas due to starting
trifluoroacetate or mesylate and products were measured. For slower
runs, the tube was placed in a constant temperature bath at 25.0 °C
between readings and then rapidly transferred to the 25.0 °C NMR
probe.
For runs at higher temperature, the tube was placed in a constant
temperature bath at the appropriate temperature. After allowing 20
s for temperature equilibration, the tube was kept in the bath for a
long period of time (minimum of 1 h) relative to the time needed
for the temperature to equilibrate. At appropriate time intervals,
the tube was then rapidly quenched in a water bath at 15 °C and
rapidly analyzed by 1H NMR at ambient temperature. The amount
of further reaction during the 10 min necessary to carry out the
NMR analysis was insignificant (less than 0.1%).
product. Cyclopropane products 24 (Ar ) C6H5) and 25 (Ar )
C6H5) were identified by NMR spectral comparison with authentic
samples.14 Substitution product 27 (Ar ) C6H5) was identified by
spectral comparison with an authentic sample of undeuterated 27,
prepared by acetylation of 15 (Ar ) C6H5) with acetic anhydride.
Traces products 28 (Ar ) C6H5)15 and 29 (Ar ) C6H5) were
identified by NMR spectral comparison with authentic samples.
Products from other solvolyses were identified by spectral analogy.
Typical spectra of products are shown as Supporting Information.
Computational Studies. Ab initio molecular orbital calculations
were performed using the Gaussian 03 series of programs.10
Structures of 32, 33, 36, and 37 were characterized as minima via
frequency calculations that showed no negative frequencies.
Supporting Information Available: Complete ref 10; the
B3LYP/6-31G* calculated structures, energies, and Cartesian
coordinates of 32, 33, and 36-38; 1H and 13C NMR of compounds
13-15, 9 (Ar ) C6H5), 9 (Ar ) p-CH3C6H4), 9 (Ar ) p-ClC6H4),
17 and 18, 19 (Ar ) C6H5), and 20-22; evolving 1H NMR spectra
1
during reaction of 9 in CD3CO2D; as well as H NMR spectral
data used in the determination of the rate of 10 (Ar ) C6H5) in
CD3CO2H. This material is available free of charge via the Internet
at http://pubs.acs.org.
In the case of trifluoroacetates 9, the rate of disappearance of
the triplet at approximately δ 5.9-6.0 was monitored. For trifluo-
roacetates 19 (Ar ) p-CH3OC6H4 and p-CH3SC6H4), the rate of
disappearance of the CH3 singlets at δ 3.78 and 2.45 was monitored.
In the case of all other trifluoroacetates 10 (which contained about
25% of the cis-isomer 9), the rate of disappearance of the upfield
TMS singlet at δ -0.07 to -0.09 due to 10 was monitored. Typical
JO062668N
(14) Closs, G. L.; Moss, R. A.; Coyle, J. J. J. Am. Chem. Soc. 1962, 84,
4985.
(15) (a) Crowe, W. E.; Goldberg, D. R.; Zhang, Z. J. Tetrahedron Lett.
1996, 37, 2117. (b) Iio, H.; Ishii, M.; Tsukamoto, M.; Tokoroyama, T.
Tetrahedron Lett. 1988, 29, 5965.
3368 J. Org. Chem., Vol. 72, No. 9, 2007