Effect of the "supersilyl" group on the reactivities of allylsilanes and silyl enol ethers

Article abstract of DOI:10.1021/ol102220e

Kinetics of the reactions of allylsilanes (1) and silyl enol ethers (2) with benzhydrylium ions (3) were studied by UV-vis spectroscopy in dichloromethane at 20 °C. The less than three times higher reaction rates of the tris(trimethylsilyl)silyl compounds

Full text of DOI:10.1021/ol102220e

ORGANIC
LETTERS
2010
Vol. 12, No. 22
5206-5209
Effect of the “Supersilyl” Group on the
Reactivities of Allylsilanes and Silyl
Enol Ethers
Hans A. Laub,† Hisashi Yamamoto,‡ and Herbert Mayr*,†
Department Chemie, Ludwig-Maximilians-UniVersita¨t Mu¨nchen, Butenandtstrasse 5-13
(Haus F), 81377 Mu¨nchen, Germany, and Department of Chemistry, UniVersity of
Chicago, 5735 South Ellis AVenue, Chicago, Illinois 60637, United States
herbert.mayr@cup.uni-muenchen.de
Received September 16, 2010
ABSTRACT
Kinetics of the reactions of allylsilanes (1) and silyl enol ethers (2) with benzhydrylium ions (3) were studied by UV-vis spectroscopy in
dichloromethane at 20 °C. The less than three times higher reaction rates of the tris(trimethylsilyl)silyl compounds in comparison to the
corresponding trimethylsilyl compounds indicate that the previously reported strong electron-donating effect of the supersilyl group operates
only in the r-position and not in the ꢀ-position.
Allylsilanes and silyl enol ethers represent two important classes
of organosilanes. While allylsilanes are widely used as allylating
reagents for Lewis acid activated carbonyl compounds
(Hosomi-Sakurai reaction),1 silylated enol ethers are key
substrates for the Mukaiyama variant of aldol reactions.2
Cyclobutane rings can be formed via Lewis acid catalyzed
[2 + 2]-cycloaddition reactions of silyl enol ethers with R,ꢀ-
unsaturated esters.3 In these reactions, higher yields and
trans-selectivity were found, when the SiMe3 group was
replaced by the bulkier SiMe2tBu group.3d Utilization of the
tris(trimethylsilyl)silyl group led to the first [2 + 2] cycload-
dition of an acetaldehyde derived silyl enol ether with an
acrylic ester (Scheme 1).4
Scheme 1
.
Stepwise [2 + 2] Cycloaddition of a Silyl Enol Ether
with an Acrylic Ester
† Ludwig-Maximilians-Universita¨t Mu¨nchen.
Intrigued by the high yields and selectivities obtained by
application of the so-called “supersilyl” group for cycload-
‡ University of Chicago.
(1) (a) Hosomi, A.; Sakurai, H. J. Am. Chem. Soc. 1977, 99, 1673–
1675. (b) Chabaud, L.; James, P.; Landais, Y. Eur. J. Org. Chem. 2004,
3173–3199. (c) Sarkar, T. K. In Science of Synthesis, Houben-Weyl Methods
of Molecular Transformations; Fleming, I., Ed.; Thieme: Stuttgart, 2002;
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(2) (a) Mukaiyama, T.; Narasaka, K.; Banno, K. Chem. Lett. 1973, 1011–
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(g) Mahrwald, R. Chem. ReV. 1999, 99, 1095–1120.
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10.1021/ol102220e  2010 American Chemical Society
Published on Web 10/26/2010

dition reactions, the corresponding tris(trimethylsilyl)silyl
enol ethers were used for Mukaiyama aldol reactions.5 High
diastereoselectivities and yields were even obtained with
acetaldehyde-derived substrates. Moreover, sequential reac-
tions with diverse reagents opened the pathway to the facile
synthesis of molecules with substructures known for their
biological activity.5c-f
log k(20 °C) ) s(N + E)
(1)
In this investigation, benzhydrylium ions 3a-f (Table 2)
with electrophilicity parameters E ranging from -5 to +1.5
Table 2. Reference Electrophiles Utilized for Quantifying the
Nucleophilicities of 1 and 2
The observed reactivities have been explained by the steric
demand and the electronic properties of the tris(trimethyl-
silyl)silyl group. Bock and co-workers reported that the first
v
vertical ionization energies (IE1 ) for supersilyl-substituted
benzenes are much smaller than those of the corresponding
trimethylsilyl derivatives (Table 1); the supersilyl group has,
Table 1. First Vertical Ionization Energies for Silyl-Substituted
Benzenes Reported by Bock and Coworkers6
therefore, been considered as a very strong electron donor.6
As demonstrated by the last entry of Table 1, the hypercon-
jugative effect of the trimethylsilylmethyl substituent causes
a slightly weaker decrease of the ionization energy. In
contrast, hydride abstractions from trialkylsilanes and tris-
(trimethylsilyl)silane have been reported to proceed with
comparable rates.7
a Empirical electrophilicities E of reference electrophiles from ref 8a.
were used because they reacted with the organosilanes 1 and
2 with conveniently measurable rates.
Compounds 1b and 2b reacted with the colored benzhy-
drylium salt 3f-BF4 in CH2Cl2 to give the desilylated products
5 (Scheme 2), as previously reported for the corresponding
trimethylsilyl compounds.8a,9,10
Kinetic investigations of the nucleophilicities of allylsi-
lanes and silyl enol ethers with Si(SiMe3)3 substitution have
so far not been performed.
We now report on the application of the benzhydrylium
method8 for characterizing the nucleophilic reactivities of
the tris(trimethylsilyl)silyl-substituted allyl compounds 1 and
enol ethers 2 and the comparison with the corresponding
allyltrimethylsilanes8a,9 and trimethylsilyl enol ethers.8a,10
(5) (a) Boxer, M. B.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128, 48–
49. (b) Boxer, M. B.; Yamamoto, H. Nat. Protoc. 2006, 1, 2434–2438. (c)
Boxer, M. B.; Yamamoto, H. J. Am. Chem. Soc. 2007, 129, 2762–2763.
(d) Boxer, M. B.; Yamamoto, H. Org. Lett. 2008, 10, 453–455. (e) Boxer,
M. B.; Akakura, M.; Yamamoto, H. J. Am. Chem. Soc. 2008, 130, 1580–
1582. (f) Boxer, M. B.; Albert, B. J.; Yamamoto, H. Aldrichimica Acta
2009, 42, 3–15. (g) Yamaoka, Y.; Yamamoto, H. J. Am. Chem. Soc. 2010,
132, 5354–5356. (h) Albert, B. J.; Yamamoto, H. Angew. Chem., Int. Ed.
2010, 49, 2747–2749.
(6) Bock, H.; Meuret, J.; Baur, R.; Ruppert, K. J. Organomet. Chem.
1993, 446, 113–122.
(7) Mayr, H.; Basso, N.; Hagen, G. J. Am. Chem. Soc. 1992, 114, 3060–
3066.
(8) (a) Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker,
B.; Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. J. Am.
Chem. Soc. 2001, 123, 9500–9512. (b) Lucius, R.; Loos, R.; Mayr, H.
Angew. Chem., Int. Ed. 2002, 41, 91–95. (c) Mayr, H.; Kempf, B.; Ofial,
A. R. Acc. Chem. Res. 2003, 36, 66–77. (d) Mayr, H.; Ofial, A. R. In
Carbocation Chemistry; Olah, G. A., Prakash, G. K. S., Eds.; Wiley:
Hoboken, NJ, 2004; Chap. 13, pp 331-358. (e) Mayr, H.; Ofial, A. R.
Pure Appl. Chem. 2005, 77, 1807–1821. (f) Mayr, H.; Ofial, A. R. J. Phys.
Org. Chem. 2008, 21, 584–595. (g) Richter, D.; Hampel, N.; Singer, T.;
Ofial, A. R.; Mayr, H. Eur. J. Org. Chem. 2009, 3203–3211.
(9) Nucleophilicities of allylsilanes were determined by using the
benzhydrylium method: Hagen, G.; Mayr, H. J. Am. Chem. Soc. 1991, 113,
4954–4961.
Benzhydrylium ions with variable p- and m-substituents,
which cover a broad range of reactivity while the steric
shielding of the reaction center is kept constant, have been
used as reference electrophiles for the construction of a
comprehensive nucleophilicity scale based on eq 1, in which
electrophiles are characterized by one parameter (E) and
nucleophiles are characterized by the solvent-dependent
parameters s (sensitivity) and N (nucleophilicity).8a
(10) Nucleophilicity parameters for silyl enol ethers determined by using
the benzhydrylium method: Burfeindt, J.; Patz, M.; Mu¨ller, M.; Mayr, H.
J. Am. Chem. Soc. 1998, 120, 3629–3634.
Org. Lett., Vol. 12, No. 22, 2010
5207

Scheme 2
.
Reactions of 1b and 2b with the Benzhydrylium Salt
Table 3. Second-Order Rate Constants for the Reactions of 1a
(1.4 × 10-4 to 5.2 × 10-4 M) with Different Benzhydrylium
Salts 3b-MXn+1 (1.6 × 10-5 to 2.3 × 10-5 M)
3f-BF4
k2/M-1 s-1
-
MXn+1
-
BCl4
BF4
84.9
74.8
77.5
85.0
-
-
GaCl4
SnCl5
-
The rate-determining formation of the C-C bond is
furthermore supported by the independence of the rate
-
constants of the concentration of Bu4N+BCl4 (Table 4).
Table 4. First-Order Rate Constants for the Reactions of 1a
with 3b-BCl4 (1.9 × 10-5 M) in the Presence of Various
As the intermediates 4 and the products 5 are colorless,
the nucleophilic attack at the electrophilic center was
followed spectrophotometrically. Addition of at least 7 equiv
of the supersilanes 1 and 2 to solutions of the benzhydrylium
tetrahaloborates, tetrachlorogallates, or pentachlorostannates
3-MXn+1 in CH2Cl2 led to monoexponential decays of the
electrophiles’ absorbances (Figure 1).
Amounts of Bu4N+BCl4
-
[1a]0/M
[Bu4N+BCl4-]0/[1a]0
kobs/s-1
1.87 × 10-4
1.85 × 10-4
1.84 × 10-4
1.84 × 10-4
0
1
5
1.76 × 10-2
1.73 × 10-2
1.77 × 10-2
1.77 × 10-2
100
Table 5 compares the second-order rate constants for the
attack of the nucleophiles 1 and 2 at the reference electro-
philes with the previously reported values for the corre-
sponding trimethylsilanes 6 and 7.9,10
Plots of log k2 for the reactions of the supersilylated
nucleophiles 1 and 2 with the reference electrophiles 3 versus
the empirical electrophilicity parameters E are linear (Figure
2), indicating that eq 1 is applicable, thus providing the N
and s parameters for the supersilyl derivatives 1 and 2
(Scheme 3).
Table 5 and Scheme 3 show that the allylsilanes 1 which
carry supersilyl groups are less than 2-times more nucleo-
philic than the structurally analogous allyltrimethylsilanes
6. Exchange of SiMe3 by Si(SiMe3)3 has also a marginal
effect on the reactivities of enol ethers. While the acetone-
Figure 1. Exponential decay of the absorbance at 513 nm during
the reaction of 1a (c ) 3.16 × 10-4 M) with 3b-SnCl5 (c ) 2.09
× 10-5 M) at 20 °C in CH2Cl2. Inset: Determination of the second-
order rate constant k2 ) 85.0 M-1 s-1 as the slope of the correlation
between the first-order rate constant kobs and the concentration of
1a.
The resulting first-order rate constants kobs correlated
linearly (with R2 values ranging from 0.935 to 0.9999) with
the concentrations of the nucleophiles 1 and 2 as depicted
in Figure 1. The second-order rate constants k2 given in
Tables 3 and 5 were derived from the slopes of such
correlations.
Table 3 shows that the rates of the reactions of allyltris-
(trimethylsilyl)silane (1a) with the benzhydryl cation 3b are
only slightly affected by the counterion, indicating the rate-
determining formation of intermediate 4 (Scheme 2) as
previously observed for the corresponding trimethylsilyl
compounds.9,10
Figure 2. Plots of log k2 for the reactions of 1 and 2 with
benzhydrylium ions 3 in CH2Cl2 at 20 °C versus the corresponding
electrophilicity parameters E.
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Org. Lett., Vol. 12, No. 22, 2010

Table 5. Second-Order Rate Constants k2 for the Reactions of the Silanes 1, 2, 6, and 7 with the Benzhydrylium Ions 3
a Data from ref 8a if not stated otherwise. b Calculated by using the Eyring equation with k2 values for temperatures varying from -71 to -22 °C (for
details see Supporting Information). c Calculated by using eq 1 from N and s in ref 8a and E from Table 2.
Scheme 3 shows that with the exception of 1a/6a the
supersilyl derivatives 1b and 2a-c generally have smaller s
values than the corresponding trimethylsilyl derivatives 6b
and 7a-c. As a consequence, the Si(SiMe3)3/SiMe3 ratio can
be expected to decrease slightly, when the electrophilicity
of the reaction partner is increased.
Scheme 3. Nucleophilicities of 1 and 2 Compared to the
Corresponding Allyltrimethylsilanes 6 and Trialkylsilyl Enol
Ethers 7a
The kinetic data in Table 5 and Scheme 3 show that the
exchange of SiMe3 by Si(SiMe3)3 in allylsilanes and silylated
enol ethers has little effect on the rates of reactions of these
electron-rich π-nucleophiles. The significantly lower first
vertical ionization energies of tris(trimethylsilyl)silyl-
substituted benzenes compared to the trimethylsilyl ana-
logues, which indicates a stronger R-effect of the Si(SiMe3)3
group compared with SiMe3, obviously does not have a
consequence for the reactivities of allylsilanes and silylated
enol ethers bearing the supersilyl group.
One can, therefore, conclude that the high selectivities
observed for [2 + 2] cycloadditions and aldol reactions with
supersilyl-substituted enol ethers cannot be attributed to
electronic effects but are due to the steric bulk and the
umbrella like structure created by the Si(SiMe3)3 group.
a s values given in parentheses.
Acknowledgment. We thank Tobias A. Nigst and Dr.
Armin R. Ofial (both Mu¨nchen) for helpful discussions, the
Deutsche Forschungsgemeinschaft (SFB 749) for financial
support, and the A. v. Humboldt Foundation for a Humboldt
Research Award (to H. Y.).
derived enol ether 2b is 2-3 times more reactive than 7b,
the cyclohexanone-derived enol ether 2c is even slightly less
reactive than 7c. The somewhat reduced reactivity of 2c
might be explained by the shielding of the reaction center
by the tris(trimethylsilyl)silyl group in the preferred confor-
mation of the cyclohexenyl ether. The slightly higher ratios
for the acetaldehyde-derived enol ethers 2a/7a may be due
to the fact that 7a bears the Si(i-Pr)3 group instead of the
SiMe3 group.
Supporting Information Available: Details of product
characterization and the kinetic experiments. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL102220E
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