Dual role of silanol groups in cyclopropanation and Hiyama-Denmark cross-coupling reactions

Article abstract of DOI:10.1021/ol1002863

"Chemical Equation Presented" Di-tert-butoxy(alkenyl)silanols serve as substrates in the Simmons-Smith cyclopropanation reaction furnishing the corresponding di-tertbutoxy(cyclopropyl)silanols, which may be Included In a Hiyama-Denmark cross-coupling reaction. The silanol group bears two distinct roles as it provides a directing group during the cyclopropanation and mediates the transmetalation event in the cross-coupling. The nature of the ligands on the silicon atom had a profound effect on reactivity in the cross-coupling, whereby substituting the alkoxide groups for fluorides allowed for efficient cross-coupling.

Full text of DOI:10.1021/ol1002863

ORGANIC
LETTERS
2010
Vol. 12, No. 6
1348-1351
Dual Role of Silanol Groups in
Cyclopropanation and Hiyama-Denmark
Cross-Coupling Reactions
Louis-Philippe B. Beaulieu, Lukas B. Delvos, and Andre´ B. Charette*
De´partement de Chimie, UniVersite´ de Montre´al, P.O. Box. 6138,
Station Downtown Montre´al, Que´bec, Canada H3C 3J7
andre.charette@umontreal.ca
Received February 3, 2010
ABSTRACT
Di-tert-butoxy(alkenyl)silanols serve as substrates in the Simmons-Smith cyclopropanation reaction furnishing the corresponding di-tert-
butoxy(cyclopropyl)silanols, which may be included in a Hiyama-Denmark cross-coupling reaction. The silanol group bears two distinct roles
as it provides a directing group during the cyclopropanation and mediates the transmetalation event in the cross-coupling. The nature of the
ligands on the silicon atom had a profound effect on reactivity in the cross-coupling, whereby substituting the alkoxide groups for fluorides
allowed for efficient cross-coupling.
The cyclopropane unit continues to generate interest through
its unique bonding properties and its numerous applications
in diverse chemical transformations.1 These motifs are
present in several bioactive natural products as well as
synthetic drugs,2 which has prompted the development of
methodologies for their synthesis. The Simmons-Smith
reaction is one of the most important methods to form
cyclopropanes.3 Over the years, many variations of the
seminal reaction4 with zinc-copper couple and diiodomethane
were disclosed, thereby increasing its synthetic utility.
Notable among these is the protocol devised by Furukawa,5
which allows the preparation of the zinc carbenoid from
diethylzinc via an alkyl exchange with diiodomethane in
various solvents. This landmark led to the development of
other carbenoids, namely Zn(CH2Cl)2,6 CF3CO2ZnCH2I,7 and
2,4,6-Cl3C6H2OZnCH2I,8 which display either increased
reactivity or stability, thus making the cyclopropanation of
relatively unreactive unfunctionalized olefins feasible. An-
other strategy to access unfunctionalized cyclopropanes relies
(4) (a) Simmons, H. E.; Smith, R. D. J. Am. Chem. Soc. 1958, 80, 5323.
(b) Simmons, H. E.; Smith, R. D. J. Am. Chem. Soc. 1959, 81, 4256.
(5) (a) Furukawa, J.; Kawabata, N.; Nishimura, J. Tetrahedron Lett. 1966,
7, 3353. (b) Furukawa, J.; Kawabata, N.; Nishimura, J. Tetrahedron 1968,
24, 53.
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Acc. 2007, 118, 597. (b) Wiberg, K. B. Acc. Chem. Res. 1996, 29, 229.
(2) (a) Pietruszka, J. Chem. ReV. 2003, 103, 1051. (b) Wessjohann, L. A.;
Brandt, W.; Thiemann, T. Chem. ReV. 2003, 103, 1625. (c) Donaldson,
W. A. Tetrahedron 2001, 57, 8589.
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Soc. 1991, 113, 723. (b) Denmark, S. E.; Edwards, J. P. J. Org. Chem.
1991, 56, 6974.
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ReV. 2003, 103, 977. (b) Charette, A. B.; Beauchemin, A. Org. React. (N.Y.)
2001, 58, 1. (c) Simmons, H. E.; Cairns, T. L.; Vladuchick, S. A.; Hoiness,
C. M. Org. React. 1973, 20, 1.
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Int. Ed. 2000, 39, 4539.
10.1021/ol1002863  2010 American Chemical Society
Published on Web 02/24/2010

Scheme 1. Synthesis of Di-tert-butoxy(alkenyl)silanols
on the use of a directing group that could later participate in
a cross-coupling reaction. Alkenylboronic esters have been
cyclopropanated with use of this approach,9,10 and the
resulting cyclopropylboronic esters have either been directly
reacted in a cross-coupling reaction11 or previously converted
to the corresponding boronic acids12 or trifluoroborates.13
Despite the recent advances14 for the cross-coupling of
readily available, stable, nontoxic, and environmentally
benign organosilanols with various electrophilic partners,
little attention has been devoted to the Simmons-Smith
cyclopropanation of alkenylsilanols. Hiyama and co-workers
have reported the synthesis of dimethyl(alkenyl)silanols, the
Simmons-Smith cyclopropanation of these substrates, and
the subsequent Tamao-Flemming oxidation of the resulting
dimethyl(cyclopropyl)silanols.15Mori and collaborators later
performed the diastereoselective Simmons-Smith cyclopro-
panation of vinylsilanols bearing a chiral silicon atom,
affording the corresponding enantiomerically enriched cy-
clopropylsilanols after a Tamao-Flemming oxidation.16
Herein we report our efforts toward the Hiyama-Denmark
cross-coupling of (cyclopropyl)silanols, whereby the bifunc-
tional silanol moiety both serves as a directing group in the
cyclopropanation step and mediates the transmetalation event
during the cross-coupling.
lanol (1) with bromobenzene using the conditions developed
by Hiyama for alkyltrifluorosilanes (eq 1).17
Unfortunately, no (()-(1S,2S)-1,2-diphenylcyclopropane (2)
was formed at the outset of the cross-coupling reaction with
either Hiyama’s conditions or those developed recently by
Denmark.13 This led us to consider modulating the nature
of the ligands on the silicon atom, such as to facilitate the
rate-limiting transmetalation step in the cross-coupling.18
DeShong19 and Denmark20 have reported an improved
efficiency of the cross-coupling of aryl- and alkenylsilanes
respectively upon increasing the electron-withdrawing char-
acter of the ligands directly bound to the silicon atom. They
argue that this operates through the facilitated formation of
the hypervalent pentacoordinated siliconate intermediate with
TBAF, since the more electrophilic substituents are better
able to stabilize the negative charge of the siliconate complex.
We thus elected to incorporate two alkoxide functionalities
onto the silicon instead of the methyl groups. Di-tert-
butoxy(alkenyl)silanols (3a-h) were readily synthesized
from the corresponding trichloro(alkenyl)silanes by using a
modified procedure developed by Kojima (Scheme 1).21 Di-
tert-butoxy(styryl)silanols (3a-e) may be accessed through
We started our investigation by attempting the cross-
coupling of (()-(dimethyl((1S,2R)-2-phenylcyclopropyl)si-
(9) Imai, T.; Mineta, H.; Nishida, S. J. Org. Chem. 1990, 55, 4986.
(10) Pietruszka, J. R.; Widenmeyer, M. Synlett 1997, 977.
(11) Hildebrand, J. P.; Marsden, S. P. Synlett 1996, 893.
(12) Zhou, S.-M.; Deng, M.-Z.; Xia, L.-J.; Tang, M.-H. Angew. Chem.,
Int. Ed. 1998, 37, 2845.
(17) (a) Matsuhashi, H.; Kuroboshi, M.; Hatanaka, Y.; Hiyama, T.
Tetrahedron Lett. 1994, 35, 6507. (b) Matsuhashi, H.; Asai, S.; Hirabayashi,
K.; Hatanaka, Y.; Mori, A.; Hiyama, T. Bull. Chem. Soc. Jpn. 1997, 70,
437.
(13) Fang, G.-H.; Yan, Z.-J.; Deng, M.-Z. Org. Lett. 2004, 6, 357.
(14) Denmark, S. E.; Regens, C. S. Acc. Chem. Res. 2008, 41, 1486.
(15) Hirabayashi, K.; Mori, A.; Hiyama, T. Tetrahedron Lett. 1997, 38,
461. Hirabayashi, K.; Takahisa, E.; Nishihara, Y.; Mori, A.; Hiyama, T.
Bull. Chem. Soc. Jpn. 1998, 71, 2409.
(18) Denmark, S. E. J. Org. Chem. 2009, 74, 2915.
(19) (a) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 1684.
(b) Handy, C. J.; Manoso, A. S.; McElroy, W. T.; Seganish, W. M.;
DeShong, P. Tetrahedron 2005, 61, 12201.
(16) Yamamura, Y.; Toriyama, F.; Kondo, T.; Mori, A. Tetrahedron:
Asymmetry 2002, 13, 13.
(20) Denmark, S. E.; Neuville, L.; Christy, M. E. L.; Tymonko, S. A.
J. Org. Chem. 2006, 71, 8500.
Org. Lett., Vol. 12, No. 6, 2010
1349

the hydrosilylation of a phenylacetylene derivative (4a-e)
followed by the alcoholysis/hydrolysis of either the isolated
(5a) or crude (5b-e) trichlorosilane. The (alkenyl)trichlo-
rosilanes (5f, 5g) are synthesized with use of a cross-
metathesis methodology developed by Fischer and collabo-
rators.22 The di-tert-butoxy(alkenyl)silanols (3f, 3g) may be
generated by using the same alcoholysis/hydrolysis proce-
dure.
Table 2. Effect of the Stoichiometry of the Reactants in the
Hiyama-Denmark Coupling
The Simmons-Smith cyclopropanation of di-tert-butoxy-
(alkenyl)silanols (3a-h) with 2.0 equiv of the preformed
zinc carbenoid bis(iodomethyl)zinc [Zn(CH2I)2] proceeded
smoothly, providing the corresponding di-tert-butoxy(cyclo-
propyl)silanols (6a-h) in excellent isolated yields (Table 1).
The (alkenyl)- and (cyclopropyl)silanols may be purified by
filtration over a pad of silica gel and stored for several months
without significant degradation, making them convenient
substrates for cross-coupling reactions.
entry
x equiv
yield (%)a
1
2
3
4
0.8
1.2
1.5
2.0
75
79
91
90
a Isolated yields.
situ.23 Gratifyingly, this led to the isolation of 2 in 75% yield
when the silanol was used as the limiting reagent (Table 2).
Increasing the amout of silanol also led to improved yields
with 1.5:1 (silanol:bromoarene) being optimal in this case.
The scope of the Hiyama-Denmark cross-coupling (Table
3) tolerated electron withdrawing (8b, 8c, 8f) and donating
(8h) groups on the aryl bromides. The reaction was compat-
ible with a variety of functional groups on both coupling
partners, namely an ester group (8b) and a ketone functional-
ity (8c), and proceeded smoothly with 3-bromopyridine (8g).
Whereas the coupling of styryl-substituted (cyclopropyl)si-
lanols could be performed with 1.5 equiv of these com-
pounds, the coupling of (cyclopropyl)silanols 6c, 6d, and
6h required a larger excess of the silanol relative to the aryl
bromide to achieve good yields.
Table 1. Cyclopropanation Scope
entry
R
yield of 6 (%)a
1
2
3
4
5
6
7
8
Ph
93 (6a)
91 (6b)
92 (6c)
89 (6d)
95 (6e)
81 (6f)
96 (6g)
88 (6h)
3-ClC6H4
4-NO2C6H4
4-OMeC6H4
2-MeC6H4
n-Bu
BnO(CH2)2
H
Table 3. Hiyama-Denmark Cross-Coupling Scope
a Isolated yields.
(()-Di-tert-butoxy((1S,2R)-2-phenylcyclopropyl)silanol
(6a) was shown to be moderately reactive in the Hiyama-
Denmark cross-coupling, with 11% isolated yield of coupling
product (2) (eq 2).
entry
x
R
Ar
yield of 8 (%)a
1
2
3
4
5
6
7
8
1.5
1.5
1.5
1.5
1.5
2.0
2.0
2.0
Ph
2-MeC6H4
4-EtOC(O)C6H4
3-FC6H4
4-CF3C6H4
3-Py
4-MeC(O)C6H4
3-ClC6H4
4-OMeC6H4
89 (8a)
70 (8b)
85 (8c)
92 (8d)
79 (8e)
63 (8f)
80 (8g)
80 (8h)
3-ClC6H4
4-NO2C6H4
4-OMeC6H4
2-MeC6H4
n-Bu
This result, despite being encouraging, still underlined the
insufficient reactivity of the organosilane in the cross-
coupling. To further increase the electrophilic nature of the
silicon atom, 6a was treated with BF3·OEt2 prior to the cross-
coupling reaction, such as to generate the trifluorosilane in
BnO(CH2)2
H
a Isolated yields.
In conclusion we have reported the synthesis of di-tert-
butoxy(vinyl)silanols, which serve as substrates in the
(21) Kojima, S.; Fukuzaki, T.; Yamakawa, A.; Murai, Y. Org. Lett. 2004,
6, 3917.
(22) (a) Pietraszuk, C.; Marciniec, B.; Fischer, H. Tetrahedron Lett. 2003,
44, 7121–7124. (b) Pietraszuk, C.; Fischer, H.; Rogalski, S.; Marciniec, B.
J. Organomet. Chem. 2005, 690, 5912.
(23) Carre´, F.; Corriu, R. J. P.; Kpoton, A.; Poirier, M.; Royo, G.; Young,
J. C.; Belin, C. J. Organomet. Chem. 1994, 470, 43.
1350
Org. Lett., Vol. 12, No. 6, 2010

Simmons-Smith cyclopropanation reaction furnishing the
corresponding di-tert-butoxy(cyclopropyl)silanols. These com-
pounds are the first (cyclopropyl)silanes to be reacted in a
Hiyama-Denmark cross-coupling. The silanol group bears
two distinct functions as it provides a directing group during
the cyclopropanation and mediates the transmetalation event
in the cross-coupling. The nature of the ligands on the silicon
atom had a profound effect on reactivity in the cross-
coupling, whereby substituting the alkoxide groups for
fluorides allowed for efficient cross-coupling. This contribu-
tion underlines the synthetic utility of silanol groups in
organic chemistry. The development of asymmetric cyclo-
propanation conditions is ongoing and will be reported in
due course.
Acknowledgment. This work was supported by NSERC
(Canada), the Canada Research Chair Program, the Canada
Foundation for Innovation, and the Universite´ de Montre´al.
L.-P.B.B. is grateful to NSERC and the Universite´ de
Montre´al for postgraduate scholarships. L.B.D. is grateful
to the JCEMolChem program for a scholarship. The authors
are also grateful to Dr. A. Lemire and F. Valle´e (Universite´
de Montre´al) for useful discussions.
Supporting Information Available: Full experimental
details and NMR spectral data for novel compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL1002863
Org. Lett., Vol. 12, No. 6, 2010
1351