Electrophilic Aromatic Substitutions of Silylated Furans and Thiophenes with Retention of the Organosilyl Group

Article abstract of DOI:10.1021/ol015810+

(matrix presented) The influence of trialkylsilyl groups on the nucleophilic reactivities of furans and thiophenes is determined by kinetic experiments.

Full text of DOI:10.1021/ol015810+

ORGANIC
LETTERS
2001
Vol. 3, No. 11
1629-1632
Electrophilic Aromatic Substitutions of
Silylated Furans and Thiophenes with
Retention of the Organosilyl Group
Mirjam Herrlich, Nathalie Hampel, and Herbert Mayr*
Department Chemie der Ludwig-Maximilians-UniVersita¨t Mu¨nchen,
Butenandtstrasse 5-13 (Haus F), D-81377 Mu¨nchen, Germany
hmy@cup.uni-muenchen.de
Received March 8, 2001
ABSTRACT
The influence of trialkylsilyl groups on the nucleophilic reactivities of furans and thiophenes is determined by kinetic experiments.
Arylsilanes usually react with electrophiles to give arenes
in which the electrophile occupies the position to which the
silyl group was previously bonded.1 This orientation has been
explained by the well-known â-stabilizing effect of silicon.2
In contrast to this general statement, examples have been
reported in which electrophilic aromatic substitution of
arylsilanes proceeds with retention of the silyl group.3
easily be introduced and replaced by electrophiles via ipso-
substitution.5a However, in 1948 Benkeser reported that
electrophilic acetylations of 2-(trimethylsilyl)furan and 2-(tri-
methylsilyl)thiophene do not proceed with ipso-substitution
but take place at the 5-position (Scheme 1).5b
Ishibashi and co-workers, for example, found that the
reaction of trimethylphenylsilane with methyl chloro(meth-
ylthio)acetate in the presence of tin(IV) chloride did not give
ipso-substitution but a mixture of disubstituted benzenes.4
In a recent review, Keay has described the use of organosilyl
moieties as blocking groups in furan chemistry, which can
Scheme 1. Acetylation of 2-(Trimethylsilyl)furan and
-thiophene.
It was the goal of this work to investigate the influence
of organosilyl groups on the reactivity of heteroarenes by
kinetic and product studies.
Treatment of the 2-silylfurans 1a-d (1.3-1.5 equiv) with
the triflate of the dianisylcarbenium ion 2a gave the furans
4 and 5 in a 2:8 to 3:7 ratio. A higher 4/5 ratio was generally
observed with the triflate of the ferrocenylphenylcarbenium
ion 2b as the electrophile (Table 1, upper half).
(1) Weber, W. P. In Silicon reagents for the Organic Synthesis; Springer-
Verlag: Berlin, 1983; Vol. 14; Chapter 8, pp 114-128.
(2) For reviews, see: Apeloig, Y. In Heteroatom Chemistry: ICHAC-
2; Block, E., Ed.; VCH: New York, 1990; pp 27-46. Apeloig, Y. In The
Chemistry of Silicon Compounds; Patai, S., Rappoport, Z., Eds.; J. Wiley
& Sons: Chichester, 1998; Vol. 1, Chapter 2, pp 57-225. Lambert, J. B.;
Zhao, Y.; Emblidge, R. W.; Salvador, L. A.; Liu, X.; So, J.-H.; Chelius, E.
C. Acc. Chem. Res. 1999, 32, 183-190. Siehl, H.-U.; Mu¨ller, T. In The
Chemistry of Silicon Compounds; Rappoport, Z., Apeloig, Y., Eds.; J. Wiley
& Sons: Chichester, 1998; Vol. 2, Chapter 12, pp 595-701.
(3) For reviews, see: Bassindale, A. R.; Glynn, S. J.; Taylor, P. G. In
The Chemistry of Silicon Compounds; Patai, S., Rappoport, Z., Eds.; J. Wiley
& Sons: Chichester, 1998; Vol. 2, Chapter 7, pp 382-388. Colvin, E. W.
Silicon in Organic Synthesis; Butterworth: London, 1981. Fleming, I. In
ComprehensiVe Organic Chemistry; Jones, N. D.; Ed.; Pergamon: Oxford
1979; Chapter 13, Vol. 3.
Though the formation of 4 and 5 was initially rationalized
by direct displacement of the silyl group in 1a-d, another
reaction mechanism is suggested by experiments conducted
(4) Ishibashi, H.; Sakashita, H.; Ikeda, M. J. Chem. Soc., Perkin Trans.
1 1992, 1953-1957.
(5) (a) Keay, B. A. Chem. Soc. ReV. 1999, 28, 209-215. (b) Benkeser,
R. A.; Currie, R. B. J. Am. Chem. Soc. 1948, 70, 1780-1782.
10.1021/ol015810+ CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/04/2001

Table 1. Reactions of Silylated Furans with Benzhydryl Cations (CH2Cl2)a-c
ratiod
SiR3
3
4
5
yield, %e
Reactions in the Absence of Proton Sponge
SiMe3
SiEt3
SiBu3
1a
1b
1c
1d
An2CH+
FcPhCH+
An2CH+
FcPhCH+
An2CH+
FcPhCH+
An2CH+
FcPhCH+
2a f
2bg
2a
2b
2a
0 °C
rt
0 °C
rt
0 °C
rt
rt
29
74
26
80
20
90
31
91
71
26
74
20
80
10
69
9
85
89
99
72
80
99
84
72
2b
2a
t
SiMe2 Bu
2b
rt
Reactions in the Presence of Proton Spongeh
SiMe3
SiEt3
SiBu3
1a
1b
An2CH+
FcPhCH+
An2CH+
2a
2b
2a
2b
2b
2a
2b
-20 °C
0 °C
-20 °C
rt
93
97
99
99
99
7
3
1
1
1
57i
66j
72
77
63
64
71
FcPhCH+
FcPhCH+
An2CH+
1c
1d
rt
t
SiMe2 Bu
-20 °C
rt
100
100
FcPhCH+
a An ) p-CH3OC6H4-. b Fc ) ferrocenyl. c The reactions were performed as described in ref 8, but the workup was modified. It involved quenching with
15 mL of concentrated ammonia, separation of the two layers and extraction of the aqueous layers with CH2Cl2 (3 × 30 mL), washing of the combined
organic layers with water, and, finally, drying over MgSO4. d The ratios were determined from the 1H NMR spectra of the crude products. e The yields with
respect to 2 were determined from the 1H NMR spectra of the crude products using mesitylene as an internal standard. For the calculation it was considered
that 2 equiv of 2 is needed for the formation of 5. f From 2a-Cl and Me3SiOTf, for 2a-Cl, see: Schneider, R.; Mayr, H.; Plesch, P. H. Ber. Bunsen-Ges. Phys.
Chem. 1987, 91, 1369-1374. g From 2b-OAc and Me3SiOTf, for 2b-OAc, see: Mayr, H.; Rau, D. Chem. Ber. 1994, 127, 2493-2498. h 2 equiv of 2,6-
di-tert-butylpyridine per mole of electrophile. i 39% of Ar2CHOH from hydrolysis of 2 was identified in the crude product. j 20% of Ar2CHOH from hydrolysis
of 2 was identified in the crude product.
in the presence of 2,6-di-tert-butylpyridine as a proton sponge
(Table 1, bottom). In all cases the disubstituted furan 3 is
observed as the almost exclusive product, indicating that
compounds 4 observed in the experiments without proton
sponge are produced via protodesilylation of 3. Since the
bis-substitution products 5 are produced in very small
amounts in the presence of the proton sponge, their formation
in the absence of the hindered pyridine must be due to attack
of the benzhydryl cations at 4 and not at 3.
negative value of σp+ ) -0.099 as well as with Apeloig’s10
conclusion that the carbenium ion stabilization of silyl groups
is between that of alkyl groups and hydrogen.
Scheme 2. Rate Constants for the Attack of the
Ferrocenylphenylcarbenium Ion 2b at 2-Trialkylsilyl-Substituted
Furans (20 °C, CH2Cl2)a
Benzhydryl cations, which can be detected photometrically
as described previously,6 can be used as reference electro-
philes to link the kinetic data of this work to reactivity data
for other classes of compounds.7 The increased reactivities
of the 2-(trialkylsilyl)furans 1a-c compared to furan (Scheme
2) do not reflect the activation of the ipso-position by
trialkylsilyl but reflect the effect of the 2-silyl substituent
on the reactivity of position 5.
The weak acceleration of electrophilic attack at the
5-position by 2-trimethylsilyl is in accord with the slightly
(6) For detailed information, see: Mayr, H.; Schneider, R.; Schade, C.;
Bartl, J.; Bederke, R. J. Am. Chem. Soc. 1990, 112, 4446-4454.
(7) For reviews, see: Mayr, H.; Patz, M. Angew. Chem. 1994, 106, 990-
1010; Angew. Chem., Int. Ed. Engl. 1994, 33, 938-957. Mayr, H.; Kuhn,
O.; Gotta, M. F.; Patz, M. J. Phys. Org. Chem. 1998, 11, 642-654. Mayr,
H.; Patz, M.; Gotta, M. F.; Ofial, A. R. Pure Appl. Chem. 1998, 70, 1993-
2000.
a The rate constants were determined photometrically as described
in ref 6. b Partial rate constant. The actually measured rate constant
is 0.0183 L mol-1 s-1, from ref 8.
1630
Org. Lett., Vol. 3, No. 11, 2001

To elucidate the effect of the trialkylsilyl groups on the
rate of ipso-substitution,11 we investigated the reactivities
of 2-methyl-5-(trialkylsilyl)furans. The reactions occur ex-
clusively with electrophilic attack at the silyl-substituted
position and proceed with similar rates as with 2-methylfuran
(Scheme 3).
Scheme 5. Reaction of 2-(Trimethylsilyl)thiophene with the
Bis(p-anisyl)carbenium Ion 2a (CH2Cl2)
Scheme 3. Rate Constants of the Reactions of the
Ferrocenylphenylcarbenium Ion 2b with
2-Methyl-5-(trialkylsilyl)furans (20 °C, CH2Cl2)a
silyl group into thiophene causes only a slight increase
+
of reactivity, in accordance with the small σp values of
SiR3.9,13
Similar substituent effects of 2-trimethylsilyl groups on
the nucleophilic reactivities of furan and thiophene toward
the tricarbonyliron-coordinated cyclohexadienylium ion have
been reported.14 Since these experiments have not been
performed in the presence of a proton sponge, the site of
initial electrophilic attack is not clear and the interpretation
of these results may require revision.
a The rate constants were determined photometrically as described
in ref 6. b From ref 8.
The negligible kinetic “ipso”-effect derived from the
comparison of 2-(trimethylsilyl)thiophene with 2,5-bis(tri-
methylsilyl)thiophene and from the comparison of 2-meth-
ylthiophene with 2-methyl-5-(trimethylsilyl)thiophene (Scheme
6) again suggests that the electronic acceleration of the ipso-
attack by SiR3 is compensated by steric retardation.
The acceleration of the electrophilic attack by hyper-
conjugative stabilization of the resulting carbenium ion,
which is observed in protodesilylations of silylated ben-
zenes,12 is obviously compensated by the steric shielding of
the organosilyl group (Scheme 4).
Scheme 6. Rate Constants for the Attack of
Bis(p-anisyl)carbenium Ion 2a at Differently Substituted
Thiophenes (20 °C, CH2Cl2)a
Scheme 4. Rate Constants for the Attack of the
Ferrocenylphenylcarbenium Ion 2b at 2-(Trimethylsilyl)furan
and 2,5-Bis(trimethylsilyl)furan (20 °C, CH2Cl2)a
a The rate constants were determined photometrically as described
in ref 6. b Partial rate constant. The actually measured rate constant
is 0.366 L mol-1 s-1
.
a The rate constants were determined photometrically as described
in ref 6. b Partial rate constants. The actually measured rate constants
are 0.0767 and 0.110 L mol-1 s-1, respectively. c From ref 8.
Similar observations were made in electrophilic reactions
of analogous thiophenes with the bis(p-anisyl)carbenium ion
(2a). The reaction of the bis(p-anisyl)carbenium triflate 2a‚
-
OTf with 2-(trimethylsilyl)thiophene in the presence of a
proton sponge gave the 2,5-disubstituted thiophene 6 shown
in Scheme 5 as the only isolable product.
As in the furan series, introduction of the trimethyl-
Introduction of a trialkylsilyl group to the 2-position of
furan or thiophene hardly affects the reactivity of this position
toward carbenium ions (ipso-attack), while the 5-position is
somewhat activated. For that reason, carbocations preferen-
tially attack the 5-position of 2-(trialkylsilyl)furans and
(8) Gotta, M. F.; Mayr, H. J. Org. Chem. 1998, 63, 9769-9775.
(9) Taylor, R. Electrophilic Aromatic Substitution; J. Wiley & Sons:
Chichester, 1990; p 461.
(10) Apeloig, Y.; Stanger, A. J. Am. Chem. Soc. 1985, 107, 2806-
2807.
(13) Glyde, E.; Taylor, R. J. Chem. Soc., Perkin Trans. 2 1973, 1632-
1635.
(11) Brook, M. A.; Neuy, A. J. Org. Chem. 1990, 55, 3609-3616.
(12) Eaborn, C. J. Organomet. Chem. 1975, 100, 43-57.
(14) John, G. R.; Kane-Maguire, L. A. P.; Odiaka, T. I.; Eaborn, C. J.
Chem. Soc., Dalton Trans. 1983, 1721-1727.
Org. Lett., Vol. 3, No. 11, 2001
1631

-thiophenes to give 2,5-disubstituted heteroarenes which are
protodesilylated in the absence of a proton trap.
Supporting Information Available: Spectroscopic data
for compounds 3 and 6. This material is available free of
charge via the Internet at http://pubs.acs.org.
Acknowledgment. We thank the Deutsche Forschungs-
gemeinschaft and the Fonds der Chemischen Industrie for
financial support.
OL015810+
1632
Org. Lett., Vol. 3, No. 11, 2001