Silanediol hydrogen bonding activation of carbonyl compounds

Article abstract of DOI:10.1002/chem.201101492

Geo-inspired activation: The first example of silanediols activating amide and aldehyde substrates through hydrogen bonding is described. Both NMR and X-ray co-crystallization studies demonstrate binding modes and affinity, and show that silanediol hydrogen-bonding assemblies can be modulated by the addition of carbonyl compounds. These silanols show catalysis in a Diels-Alder reaction and provide insight into the design of new organocatalysts (see figure). Copyright

Full text of DOI:10.1002/chem.201101492

COMMUNICATION
DOI: 10.1002/chem.201101492
Silanediol Hydrogen Bonding Activation of Carbonyl Compounds
Ngon T. Tran, Taewoo Min, and Annaliese K. Franz*[a]
Silicon is the second most abundant element on the
earthꢀs surface, whereby inorganic silanols (SiOH) make up
the reactive hydroxyl groups on the surface of minerals, zeo-
lites, and silica gel. The acidic silanol groups[1] are known to
be capable of hydrogen bonding to small molecules for het-
erogeneous catalysis and separation chemistry, but the dis-
crete surface-molecule interactions are not well under-
stood.[2] Silanediols R2Si(OH)2 are of particular interest as
they contain a geminal diol bonding motif that is not com-
monly accessible for carbon analogues, but they represent a
synthetic challenge due to their rapid rates of self-condensa-
tion. While condensation is advantageous for the synthesis
of siloxane polymers, metallosiloxanes, and silesquioxanes,[3]
it creates a barrier that may hinder researchers from explor-
ing the properties and applications of discrete silanediols.[4]
Recent studies demonstrate that silanols can function as iso-
steres and transition-state analogues in drug design, in
which the enhanced acidity of the silanol can improve bind-
ing to a receptor.[5] Small molecules containing silanol and
silanediol groups may be useful as models to understand
local surface sites and reactivity of silica materials for catal-
ysis, and also to design new homogeneous small-molecule
catalysts.
We seek to understand the hydrogen bonding patterns
and interactions between organic silanediols with carbonyls
for applications to catalysis and molecular recognition. Hy-
drogen bonding interactions play an important role in mo-
lecular recognition and metal-free catalysis, and are fre-
quently used in nature for structural organization and
enzyme activity.[6] Previous structural studies have demon-
strated the hydrogen bonding networks that silanediols can
attain through dual donor and acceptor interactions,[4,7] and
also the ability to hydrogen bond with chloride anions for
molecular recognition.[8] Studies of silanetriols have shown
that amines can complex with and stabilize silanetriols.[9]
Here we describe the synthesis and structural studies of
organic silanediols for small-molecule hydrogen bonding ac-
tivation of carbonyl compounds.[10] We are particularly inter-
ested in studying bulky silanediols that do not readily under-
go condensation reactions.[11] We have performed crystalliza-
tion and NMR-binding experiments to investigate the hy-
drogen bonding interactions in both solid-state and solution
for molecular recognition and the design of new catalysts.
This is the first study of neutral Lewis basic carbonyl com-
pounds with silanediols.
We have synthesized a series of bulky silanediols 2–4 that
incorporate electron-withdrawing groups to enhance acidity
while incorporating steric effects to overcome condensation
reactions. Due to the synthetic challenge, the chemical space
for silanediols is largely unexplored, and silanediols 2–4 rep-
resent new structures.[4] The mesityl group (Mes) was incor-
porated to prevent formation of disiloxanediols and higher
order siloxanes.[12] Incorporating a mesityl group also pro-
vides enhanced solubility relative to the unsubstituted
phenyl analogue (1), and facilitates crystallization experi-
ments. Fluoro-substituted silanediols 3 and 4 were synthe-
sized based on the hypothesis that silanols with greater acid-
ity will exhibit stronger hydrogen bonding and more effec-
tive binding interactions.[13] The syntheses of silanediols 2–4
were performed by a Pd-catalyzed hydrolysis of the corre-
sponding silanes (5 and 6), which can each be prepared in
2–4 steps [Eq. (1) and (2)].[14] The structures of silanediols
1
were confirmed by H and 29Si NMR spectroscopy, and the
structure of silanediols 2 and 3 were unambiguously deter-
mined by single-crystal X-ray diffraction. These silanediols
are stable with no detectable condensation observed in solu-
tion and under standard storage conditions.
X-ray structures of silanediols 2 and 3 highlight the dual
capabilities as both a donor and acceptor by intermolecular
[a] N. T. Tran, T. Min, Prof. A. K. Franz
Department of Chemistry
University of Calfornia, Davis
One Shields Ave, Davis, CA 95616 (USA)
Fax : (+1)530-752-8995
E-mail: akfranz@ucdavis.edu
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101492.
Chem. Eur. J. 2011, 17, 9897 – 9900
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binding, and show the effect of sterics and electronics on the
solid-state structure (Figure 1). Due to the enhanced steric
bulk of silanediol 2, a linear polymeric network linked by
hydrogen bonding is observed. In the case of silanediol 3,
the donor–acceptor binding between two molecules forms a
dimeric cluster, which is observed to form a higher order
structure as a repeating motif of dimers linked through the
remaining hydrogen bonding sites. In addition to reduced
sterics, we have calculated silanediol 3 to be 0.5 pKa units
more acidic compared to silanediol 2.[1d] Thus, these struc-
tures show that the solid-state assembly and hydrogen bond-
ing network is readily modulated based on sterics and/or
electronics. For the linear polymeric network of silanediol 2,
the linear network for silanediol 2 is modulated by the pres-
ence of the carbonyl to now form a dimeric cluster with two
carbonyl groups involved in hydrogen bonding (Figure 2).
À
Typical SiO H···O=C distances in these structures are
À
À
1.88 ꢂ. Typical SiO H···O Si distances in these structures
are 1.95 ꢂ. The dual role of the SiOH group and dimeric
form enhances the hydrogen bonding ability of the remain-
ing OH, which leads to stronger hydrogen bonds with the
Lewis base than would be observed for the monomer. When
we performed a co-crystallization of pyridine with silanediol
2, we observed this same hydrogen bonding pattern.[15,17]
We next proceeded to study silanediol binding and activa-
tion of carbonyls in solution. The evidence for hydrogen
bonding between a carbonyl and silanol in solution phase is
provided by NMR binding studies. Molecular recognition
and formation of a hydrogen bonding complex was investi-
gated with neutral Lewis base binding partners such as
DMF and benzaldehyde, using NMR titrations in
[D6]benzene and [D]chloroform.[8] The hydroxy proton of si-
À
À
À
the typical SiO H···O Si distances are 1.95 ꢂ. Typical SiO
À
H···O Si distances in the dimeric structure of 3 are 1.93 ꢂ.
We have also demonstrated hydrogen bonding of silanediols
2–4 in solution using NMR spectroscopy, in which a strong
downfield shift (Ddꢀ1.5–2.0 ppm) of the silanol hydroxy
peak is observed at either lower temperatures or higher con-
centrations (see the Supporting Information).
To study the hydrogen bonding activation of carbonyls
with silanediols, several co-crystallization experiments were
performed.[15] X-ray diffraction structures of silanediols co-
crystallized with neutral Lewis basic carbonyls reveal that
the SiOH group of a silanediol serves as an activating group
by hydrogen bonding to a carbonyl.[16] Structures obtained
for both benzaldehyde and dimethylformamide show that
Figure 2. X-ray structure diagrams of Mes2Si(OH)2·PhCHO and
Mes2Si(OH)2·Me2NCHO. Selected hydrogen atoms in thermal displace-
ment plots, which show 50% probability displacement ellipsoids for non-
hydrogen atoms, are omitted for clarity. Selected bond parameters (bond
lengths in ꢂ, angels in 8) for Mes2Si(OH)2·PhCHO: H2..O21 1.938(19);
Figure 1. X-ray structure diagrams of silanediols 2 and 3 as a linear poly-
meric network and a dimeric cluster, respectively. Selected hydrogens in
thermal displacement plots, which show 50% probability displacement el-
lipsoids for non-hydrogens, are omitted for clarity. Selected bond param-
eters (bond lengths in ꢂ, angels in 8) for 2: H2···O1A 2.01; O2···O1A
À
À
O2···O21 2.7297(11); O2 H2···O21 174.2(17); O2···O21 C21 136. Select-
ed bond parameters (bond lengths in ꢂ, angels in 8) for
À
2.803(4); O2 H2···O1A 157.3. Selected bond parameters (bond lengths
À
À
in ꢂ, angels in 8) for 3: H2···O21 1.95(3); O2···O21 2.7804(16); O2
Mes2Si(OH)2·Me2NCHO: H1···O21 1.86(2); O1···O21 2.656(2); O1
À
H2···O21 174(3).
H1···O21 173(2); O2···O21 C21 130.
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Chem. Eur. J. 2011, 17, 9897 – 9900

Organocatalysis
COMMUNICATION
lanediol 4 exhibits a significant downfield shift (Dd=
2.51 ppm) upon addition of DMF (Figure 3). From these ex-
periments, the binding affinity of silanediols 2–4 with DMF
can be compared (Table 1). NMR studies with 4-methoxy-
benzaldehyde also show a noticeable shift (Dd=0.22 ppm)
and broadening of the signal of the hydroxy proton of the si-
lanediol. We have observed that pKa calculations correlate
with the binding constant in which the binding affinity dou-
bles with the increase of 0.8 pKa units (e.g., 2 and 4), and
dual hydrogen bonding in both silanediols and disiloxane-
diols also enhances binding affinity.
ing groups found in organocatalysts, for example, TADDOL
(a,a,a,a-tetraaryl-1,3-dioxolane-4,5- dimethanols), BINOL
(1,1-binaphthol), and thioureas, and should have similar cat-
alytic potential.[10a,18] Performing a reaction between metha-
crolein and Rawalꢀs diene[19] in the presence of a series of si-
lanols and silanediols (20 mol%) does indeed show a rate
acceleration for this reaction (Table 1); however, the en-
hanced activity was not observed to correlate with acidity or
with the dual hydrogen bonding capabilities of the silane-
diol. The reaction was performed at two temperatures to
distinguish the reactivity from the background rate. The
highest activity was observed with monosilanol Ph3SiOH
and with disiloxanediol 7, which exhibits intramolecular co-
operative hydrogen bonding and enhanced acidity. Initially,
the rates may seem to be counterintuitive based on what is
known for hydrogen bonding activation, but these results
can be correlated with our NMR and structural studies.
Based on the NMR and structural studies described here,
we hypothesize that there are many hydrogen bonding as-
semblies in equilibria, but only one (or a few) is productive
and leads to catalysis. Since silanediols have been observed
as both hydrogen bonding donors and acceptors, the mono-
silanols here are more active than silanediols and the self-as-
sociation of silanediols accounts for the lower yields ob-
served. This hypothesis may account for the trend reversal
observed for the Diels–Alder reaction even with the more
acidic fluorinated silanediols. This hypothesis provides in-
sight for organocatalysis and is consistent with results for al-
cohol/TADDOL catalysts.[20] It is expected that an organoca-
talyst undergoes self-association to form an hydrogen
bonded dimer or network, particularly when low tempera-
tures or a more acidic catalyst is utilized, which may reduce
the catalytic activity or selectivity. Therefore, when design-
ing a successful organocatalyst it is important to discourage
unproductive self-association interactions, for example,
using steric effects, additives, or reaction conditions where
self-association is reduced.
To demonstrate if the hydrogen bonding abilities of sila-
nediols translate to catalytic ability to activate electrophiles,
we selected the Diels–Alder cyclization as a test reaction.
Silanols have comparable acidity to known hydrogen bond-
Figure 3. 1H NMR of silanediol 4 with 5.0 equivalents of DMF in C6D6
shows a substantial shift (Dd=2.51 ppm) of the hydroxy peak (indicated
with *).
In summary, we have demonstrated that silanols and sila-
nediols can activate carbonyl compounds through hydrogen
bonding with implications for small-molecule catalysis and
molecular recognition. The first NMR and crystallographic
analyses of silanediols binding to carbonyl compounds pro-
vide evidence of a discrete interaction through hydrogen
bonding. These organic silanols may be envisioned as a solu-
ble form of silica gel that captures the impressive hydrogen
bonding properties of an inorganic surface onto a small-mol-
ecule scaffold. As such, these scaffolds represent important
synthetic targets and may also serve as important model sys-
tems to study the discrete surface–molecule binding interac-
tions for minerals, zeolites, and silica gel. Small-molecule si-
lanediols such as the ones described here are likely to have
widespread applications for catalysis, molecular-recognition
functions, new building blocks for supramolecular assembly,
and the synthesis of new materials using non-covalent inter-
actions to control structure. Current work is focused on de-
signing bulky chiral organic scaffolds with silanediols as acti-
vating groups for asymmetric catalysis.[21]
Table 1. Catalytic activation of carbonyl compounds by silanols and sila-
nediols.
Catalyst[a]
Yield at
À728C [%]
Yield at
À658C [%]
Ka with
pKa(H O) of
AHCTUNGTERNNUNG
2
[b]
DMF [mÀ1
]
SiOH[c]
none
silica gel
PhMe2SiOH
Ph3SiOH
2
3
<5
–
36
39
63
83
56
52
49
72
–
–
–
–
6.8Æ0.2[d]
12.0
11.7
12.4
11.9
11.6
5.9
47
53
31
40
55
55
37.3Æ3.5
43.2Æ0.1
58.7Æ0.03
90.8Æ0.2
4
7[e]
145.7Æ0.2
[a] All reactions were performed at 1.0m in toluene, with 20 mol% cata-
lyst for 2 d. [b] Binding studies were performed in C6D6. [c] Acidity cal-
culations for pKa were performed using B3LYP/6-31+G(d) and verified
by comparison to experimental values for known acids; see the Support-
ing Information for complete details. [d] See reference [1c]. [e] Silanol 7
is tetraphenyldisiloxanediol, OACTHNUGRTNE[UNG SiPh2(OH)2]2.
Chem. Eur. J. 2011, 17, 9897 – 9900
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9899

A. K. Franz et al.
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Experimental Section
Crystals were grown from slow evaporation of silanediol in a 1:1 ratio
with carbonyl compound from either benzene or dichloromethane sol-
vent. Suitable crystals were mounted on glass fibers with silicone grease
and placed in the cold N2 stream of a Bruker SMART Apex II diffrac-
tometer with graphite-monochromated MoKa radiation (l=0.71073 ꢂ) at
90(2) K. All non-hydrogen atoms were refined anisotropically. In general,
as many hydrogen atoms were located on a difference map as possible
and then the missing hydrogen atoms were added geometrically. The po-
sition and thermal parameters of hydrogen atoms were allowed to refine
freely. Crystal data and details of measurements for dimesitylsilanediol
with benzaldehyde (2·PhCHO): C18H24O2Si·C7H6O, Mr =406.58 gmolÀ1
,
0.70ꢃ0.38ꢃ0.35 mm3, monoclinic, P21/c, a=11.9575(6), b=10.4853(5),
c=17.9339(9) ꢂ, a=g=90, b=103.478(1)8, V=2186.59(19) ꢂ3, Z=4,
1calcd =1.235 MgmÀ3, m=0.13 mmÀ1, MoKa radiation, l=0.71073 ꢂ, T=
90(2) K, 2qmax =558, 23450 reflections, 5023 independent reflections
(Rint =0.019), 382 parameters, 0 restraints, full-matrix least-squares refine-
ment on F2, semiempirical absorption correction from equivalents, final
R [F2 >2s(F2)]=0.032, wR(F2)=0.092, largest difference peak and hole
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[15] Details for crystal structure analyses can be found in the Supporting
Information. CCDC-819934 (3), 819936 (2), 819935 (2·PhCHO),
819937 (2·DMF), and 819939 (2·pyridine) contain the supplementary
crystallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
We gratefully acknowledge the University of California, Davis and Na-
tional Science Foundation (CHE-0847358 and Teragrid resources provid-
ed by the Pittsburgh Supercomputer Center) for support. A.K.F. ac-
knowledges 3m Corporation for a Nontenured Faculty Award. N.T.T. and
T.M. are recipients of the Bradford Borge Chemistry Fellowship. N.T.T.
is a recipient of a Department of Education GAANN Fellowship. We ac-
knowledge Dr. J. Fettinger and Prof. M. Olmstead (UCD) for assistance
with X-ray analysis, and Prof. D. Tantillo (UCD) and Prof. J. Lee (Univ.
Rutgers) for assistance with computational studies.
Keywords: hydrogen bonds
organocatalysis · silicon
· molecular recognition ·
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Received: May 16, 2011
Published online: July 29, 2011
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