Silanediols: A new class of hydrogen bond donor catalysts

Article abstract of DOI:10.1021/ol2021115

Silanediols are introduced as a new class of hydrogen bond donor catalysts for the activation of nitroalkenes toward nucleophilic attack. Excellent yields of product are obtained for the conjugate addition of indole to β-nitrostyrene catalyzed with a stab

Full text of DOI:10.1021/ol2021115

ORGANIC
LETTERS
2011
Vol. 13, No. 19
5228–5231
Silanediols: A New Class of Hydrogen
Bond Donor Catalysts
Andrew G. Schafer, Joshua M. Wieting, and Anita E. Mattson*
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus,
Ohio 43210, United States
mattson@chemistry.ohio-state.edu
Received August 3, 2011
ABSTRACT
Silanediols are introduced as a new class of hydrogen bond donor catalysts for the activation of nitroalkenes toward nucleophilic attack. Excellent
yields of product are obtained for the conjugate addition of indole to β-nitrostyrene catalyzed with a stable, storable dinaphthyl-derived silanediol.
The preparation and structural characterization of a C2-symmetric chiral silanediol is also reported along with its ability to catalyze the conjugate
addition reaction.
Anion recognition abilities of small organic molecules
have provided a great deal of inspiration for the develop-
ment of hydrogen bonding catalysis, a powerful tool in
organic synthesis.1 Recent successes in the area of hydro-
gen bond donor (HBD) catalysis exploit the anion recog-
nition abilities offered by urea, thiourea, and guanidinium
functionalities (1).2 Expansion of anHBD catalyst scaffold
to include novel functional groups capable of recognizing
anions will afford additional classes of catalysts to explore
in overcoming the barriers associated with current HBD
catalysts, such as low catalyst turnover and limited reac-
tion scopes. Silanediols3,4 are known to associate with both
acetate (2) and chloride ions, yet they have received little
attention in the context of noncovalent catalysis.5 Excited
by the potential of these interesting molecules, we have
initiated a program in our laboratory dedicated toward
pioneering the development of silanediols as a new class of
catalysts that operate through hydrogen bonding interac-
tions. In this communication, we report initial successes
with silanediol catalysis and its application toward the
activation of nitroalkenes.
A ground-breaking report in 2006 from Kondo and co-
workers revealed a silanediol-based receptor that not only
offered an area of expansion for anion recognition but also
opened up a promising new platform for HBD catalyst
design.5,6 While the demonstrated anion recognition abil-
ities of silanediols provided encouraging support for their
development in noncovalent catalysis, our investigations
into this area began with a number of uncertainties. The
stability of silanediols was unclear, and there were con-
cerns about their preparation, purification, and ability
to withstand reaction conditions. Furthermore, while evi-
dence existed for their anion association properties,
(1) (a) Pihko, P. Hydrogen Bonding in Organic Synthesis; Wiley-VCH:
Weinheim, 2009. (b) Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107,
5713. (c) Akiyama, T. Chem. Rev. 2007, 107, 5744. (d) Taylor, M. S.;
Jacobsen, E. N. Angew. Chem., Int. Ed. 2006, 45, 1520. (e) Akiyama, T.;
Itoh, J.; Fuchibe, K. Adv. Synth. Catal. 2006, 348, 999.
(2) (a) Takemoto, Y. Org. Biomol. Chem. 2005, 3, 4299. (b) Zhang, Z.;
Schreiner, P. Chem. Soc. Rev. 2009, 38, 1187. (c) Connon, S. Synlett
2009, 354.
(3) For a review on organosilanols, please see: Chandrasekhar, V.;
Boomishankar, R.; Nagendran, S. Chem. Rev. 2004, 104, 5847.
(4) Interesting work involving silanediols as protease inhibitors has
been reported: (a) Mutahi, M. W.; Nittoli, T.; Guo, L. X.; Sieburth,
S. M. J. Am. Chem. Soc. 2002, 124, 7363. (b) Sieburth, S. M.; Chen, C. A.
Eur. J. Org. Chem. 2006, 311.
(6) During the preparation of this manuscript the following reports
involving silanediols were published: (a) Liu, M.; Tran, N. T.; Franz,
A. K.; Lee, J. K. J. Org. Chem. 2011, 76, 7186. (b) Tran, N. T.; Min, T.;
Franz, A. K. Chem.;Eur. J. 2011, 17, 9897.
(5) Kondo, S.; Harada, T.; Tanka, R.; Unno, M. Org. Lett. 2006, 8,
4621.
r
10.1021/ol2021115
Published on Web 09/06/2011
2011 American Chemical Society

whether silanediols would be capable of catalyzing a
chemical process remained unproven. The overall lack
of information surrounding this entire area was parti-
cularly attractive to us, and a program was initiated to
explore the feasibility of silanediol catalysis. We rea-
soned that the catalytic cycle would begin with activa-
tion of an electrophile, such as β-nitrostyrene (4), with
silanediol 3 to afford intermediate 5 (Scheme 1). Nu-
cleophilic addition to give rise to 6 followed by proton
transfer and release of the catalyst would complete the cycle
and generate the desired product (7). For this process to be a
success requires an appropriate balance between the hydro-
gen bond donor and acceptor: suitable electrophilic activa-
tion is necessary while still allowing for rapid catalyst
turnover. The limited knowledge available regarding hydro-
gen bonding of silanediols left this critical aspect of the
proposed cycle uncertain, and we set out to ascertain the
catalytic potential of 3.
3b for 24 h in methylene chloride suggesting the silanediol
functionality is a necessary element of the catalyst design.
Further evidence supporting silanediol 3a as an HBD
catalyst was realized from the solvent screen. Solvents able
to disrupt hydrogen bonding, such as THF and ethyl
acetate, completely shut down the catalytic activity of 3a
and gave rise to less than 10% yield of 10a (entries 3À5).
The importance of the diol functionality was reconfirmed
whentriphenylsilanol wasfound toyield 52% of 10a (entry
10). The reaction catalyzed by diphenylsilanediol was also
lower yielding (entry 11). Silanediol 3a was compared
directly to conventional urea and thiourea catalysts 11a
and 11b. Silanediol 3a easily outperformed urea 11a
affording more than one and a half times the amount of
10a after 24 h in methylene chloride (67% vs 43%, entry 6
vs 12). The yields of 10a were even better for silanediol 3a
than thiourea 11b (67% vs 58%, entry 6 vs 13).
Table 1. Optimization of Silanediol (3a) Catalysis in the Addi-
tion of Indole (9) to Nitroalkene (4) To Afford 10aa
Scheme 1. Silanediol Catalysis
The addition of indole (9) to β-nitrostyrene (4) was
selected as an ideal reaction to test the concept of silanediol
catalysis as it is a process known to be accelerated in the
presence of an appropriate HBD (Table 1).7 Silanediol 3a,
derived from 1-bromonaphthalene and silicon tetrachlor-
ide, was chosen as the initial catalyst for examination,
based upon Kondo’s discoveries of its anion recognition
properties.5 Almostimmediatelyour efforts wererewarded
when 20 mol % of 3a provided 81% of the desired product
10a after 24 h in methylene chloride (entry 2). A brief
solvent screen including toluene, ethyl acetate, and aceto-
nitrile led us to conclude methylene chloride is the best
solvent for this process (entries 1, 3À5). Reduction of the
catalyst loadings to 10 and 5 mol % afforded 67% and
30% yields, respectively, after 24 h (entries 6 and 7). In
order to probe the importance of the hydroxyl groups on
reactivity, dimethoxysilane 3b was subjected to identical
reaction conditions in the addition of 9 to 4. Just 10% of
10a was formed when 4 and 9 are exposed to 20 mol % of
entry
solvent
catalyst
3a
mol % cat.
yield (%)b
1
PhCH3
CH2C12
EtOAc
20
20
20
20
20
10
5
56
81
4
2
3a
3
3a
4
THF
3a
5
5
CH3CN
CH2C12
CH2C12
CH2C12
CH2C12
CH2C12
CH2C12
CH2C12
CH2C12
3a
4
6
3a
67
30
21
10
52
46
43
58
7
3a
8
3a
2.5
20
20
20
10
10
9
3b
10
11
12
13
Ph3SiOH
Ph2Si(OH)2
11a
11b
a Reactions performed using 1.5 equiv of indole at a concentration of
2 M. See Supporting Information for detailed experimental procedures. In
the absence of a catalyst an 8% yield of product was isolated. b Isolated yield.
(7) For reports of urea/thiourea catalyzed indole additions, see: (a)
Dessole, G.; Herrera, R. P.; Ricci, A. Synlett 2004, 13, 2374. (b) Herrera,
R. P.; Sgarzani, V.; Bernardi, L.; Ricci, A. Angew. Chem., Int. Ed. 2005,
44, 6576. (c) Fleming, E. M.; McCabe, T.; Connon, S. J. Tetrahedron
Lett. 2006, 47, 7037. (d) So, S. S.; Burkett, J. A.; Mattson, A. E. Org.
Lett. 2011, 13, 716. For examples of phosphoric acid catalyzed indole
additions, see: (a) Rowland, G. B.; Rowland, E. B.; Liang, Y.; Perman,
J. A.; Antilla, J. C. Org. Lett. 2007, 9, 2609. (b) Itoh, J.; Fuchibe, K.;
Akiyama, T. Angew. Chem., Int. Ed. 2008, 120, 4016.
With the demonstrated activity of unique HBD catalyst
3a in hand, attention was turned toward evaluating the
scope of the reaction with respect to both the nitroalkene
and indole (Table 2). Both electron-donating and electron-
withdrawing substituents on the nitrostyrene were well
Org. Lett., Vol. 13, No. 19, 2011
5229

accommodated in the process. The addition of indole and
5-methoxyindole to 4-bromonitrostyrene and 4-methoxy-
nitrostyrene catalyzed by 3a enabled the isolation of 98%
of 10b and 82% of 10c, respectively (entries 2 and 3). The
more challenging alkyl nitroalkenes were discovered to
afford good yields of product with 20 mol % of 3a after 48
h at 23 °C in methylene chloride. The addition of 5-meth-
oxyindole to the hexanal-derived nitroalkene yielded 44%
of 10d based upon 49% conversion after stirring for 24 h
(entry 4). The more hindered cyclohexanecarboxaldehyde-
derived nitroalkene was also tolerated in the reaction
giving rise to 48% of 10e (entry 5). Electron-rich 5-meth-
oxyindole operated well as a nucleophile in the addition to
nitrostyrene affording 99% of 10f (entry 6). 5-Chloroin-
dole, albeit somewhat more sluggish, also proved to be a
useful nucleophile in the addition reaction yielding 71% of
10g after 48 h (entry 7).
Scheme 2. Synthesis of Silanediol Catalyst (()-17a
conversion of 13 to the aryl iodide 14 was executed with
ICl in good yield (85%). Cross-coupling of the aryl
iodide with phenyl boronic acid gave rise to the desired
substituted dibromobinaphthalene 15 in 85% yield.
Finally, the lithium halogen exchange of 15 effected with
n-BuLi followed by treatment with silicon tetrachloride
generated the dichlorosilane 16 in situ which was then
hydrolyzed to silanediol 17a upon subjection to ether
and water.
Table 2. Silanediol Catalysis Substrate Scopea
3a
time
(h)
yieldb
(%)
entry
R
R1
product mol %
1
2
3
4c
5
6
7
Ph
4-Br-C6H4
4-MeO-C6H4 MeO
H
10a
10b
10c
10d
10e
10f
20
20
20
20
20
10
20
24
48
24
24
48
48
48
81
98
82
44
48
99
71
H
n-pentyl
cyclohexyl
Ph
MeO
H
MeO
C1
Ph
10g
a Reactions performed using 1.5 equiv of indole at a concentration of
2 M. See Supporting Information for detailed experimental procedures.
b Isolated yield. c Based on 49% conversion.
Once the potential of silanediol catalysis had been estab-
lished, efforts to address the interesting and unprecedented
challenge of synthesizing chiral silanediols were initiated.
Based upon our success with dinaphthyl-derived silanediol
3a, we reasoned a binaphthyl scaffold would provide an
ideal starting point for the investigations and we set out to
prepare 17a (Scheme 2). Prior to this study, the construc-
tion of C2-symmetric silanediols had not been reported. A
modular route taking advantage of a SuzukiÀMiyaura
cross-coupling reaction to install substitution on the bi-
naphthalene backbone was favored to provide the oppor-
tunitity of future access to a family of chiral silanediols from
a common intermediate (14). The preparation of racemic
silanediol 17a began by treating dibromobinaphthalene
(12) with lithium tetramethylpiperidide (LiTMP) and
trimethylsilyl chloride (TMSCl) to generate 13.8 The
Figure 1. ORTEP representation of 17a. Ellipsoids are displayed
at 50% probability.
Crystallization of 17a from hexanes and methylene chlor-
ide gave rise to X-ray quality crystals for analysis (Figure 1).
To the best of our knowledge this is the first reported crystal
structure of a C2-symmetric chiral silanediol. A comparison
of silanediols 3a and 17a revealed the SiÀO and SiÀC
bond lengths are roughly equivalent in both structures.
(8) Widhalm, M.; Aichinger, C.; Mereiter, K. Tetrahedron Lett. 2009,
50, 2425. See Supporting Information for detailed expeimental
procedures.
5230
Org. Lett., Vol. 13, No. 19, 2011

In summary, silanediols have been introduced as a new
class of hydrogen bond donor catalysts for the activation
of nitroalkenes in conjugate addition reactions. This study
not only includes the original report of silanediol catalysis
but also reveals the first synthesis and examination of a
modular C2-symmetric chiral silanediol, including a crystal
structure. Investigations surrounding the potential asso-
ciated silanediol catalysis, including the development of
enantioselective variants, as a new tool for organic synth-
esis are ongoing in our laboratory and will be reported as
soon as possible.
Scheme 3. Catalysis with Silanediol (()-17a
The difference in bond angles between the two catalysts is
more substantial: silanediol 17a has significantly smaller
CÀSiÀC (92.53° vs 110.14°) and OÀSiÀO (106.08° vs
110.43°) bond angles than 3a. A torsional angle of 37.09°
was found for C3ÀC2ÀC18ÀC19 of 17a.9
Acknowledgment. Support for this work has been pro-
vided by the OSU Department of Chemistry. We thank the
Ohio BioProducts Innovations Center (OBIC) for helping
support our mass spectrometry facility. Dr. Judith Galluc-
ci (OSU) is thanked for solving the crystal structure of
silanediol 17a.
The catalytic potential of (()-17a was put to the test in
the addition of 5-methoxyindole to β-nitrostyrene, a 55%
yield of desired adduct 10f after 24 h at 23 °C in methylene
chloride (Scheme 3).
Supporting Information Available. Experimental pro-
cedures and spectral data (PDF). This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
(9) See Supporting Information for more details regarding the crystal
structure of 17a.
Org. Lett., Vol. 13, No. 19, 2011
5231