Ortho-silylated derivatives of tetrakis(2-hydroxyphenyl)ethene: A sterically isolated structural model for oxo-surface binding domains

Article abstract of DOI:10.1021/ol801427w

(Chemical Equation Presented) The introduction of sterically isolating ortho-trialkylsilyl, -aryldialkylsilyl, and -diarylalkylsilyl substituents onto the structurally preorganized tetrakis(2-hydroxyphenyl)ethene ligand framework has been accomplished by a 4-fold retro-Brook rearrangement. Installation of the most sterically demanding silyl substituents required the development of an iterative procedure, involving successive double silylation/metalation/ migration sequences without the isolation of intermediates. This system was designed to function as a soluble structural model for the planar binding domains of heterogeneous oxo-surfaces of silica and alumina supports.

Full text of DOI:10.1021/ol801427w

ORGANIC
LETTERS
2008
Vol. 10, No. 17
3825-3828
Ortho-Silylated Derivatives of
Tetrakis(2-hydroxyphenyl)ethene: A
Sterically Isolated Structural Model for
Oxo-Surface Binding Domains
Mee-Kyung Chung, Owen C. Lightbody, and Jeffrey M. Stryker*
Department of Chemistry, UniVersity of Alberta, Edmonton, Alberta T6G 2G2, Canada
jeff.stryker@ualberta.ca
Received July 6, 2008
ABSTRACT
The introduction of sterically isolating ortho-trialkylsilyl, -aryldialkylsilyl, and -diarylalkylsilyl substituents onto the structurally preorganized
tetrakis(2-hydroxyphenyl)ethene ligand framework has been accomplished by a 4-fold retro-Brook rearrangement. Installation of the most
sterically demanding silyl substituents required the development of an iterative procedure, involving successive double silylation/metalation/
migration sequences without the isolation of intermediates. This system was designed to function as a soluble structural model for the planar
binding domains of heterogeneous “oxo-surfaces” of silica and alumina supports.
Structurally preorganized polydentate organic ligands provide
metal coordination domains appropriate for a range of
applications in catalysis, supramolecular chemistry, and
materials science. Covalent and conformational constraints
engineered into the ligand can predispose the nucleation of
unusual and reactive coordination arrays inaccessible using
conventional ligand designs.
the tetrakis(2-hydroxyphenyl)ethene ligand inhibits inward
collapse, promoting the assembly of bridged polymetallic
coordination arrays over lower nuclearity chelated structures.4
The tetrakis(2-hydroxyphenyl)ethene ligand system1 (I) is
a differentially constrained analogue of the more familiar
calix[4]arene structural class (II).2 Despite considerable steric
congestion, the ligand retains a significant degree of con-
formational mobility, undergoing rapid (but presumably
correlated3) rotation at room temperature. In contrast to the
calixarene macrocycle, the relatively rigid ethylene core of
The conformation that situates the four aryloxy rings
perpendicular to the ethylene plane and the four oxygen
residues in the same hemisphere, as shown in structure I,
provides a roughly square planar arrangement of the aryloxy
binding sites and a coordination environment that models
the “oxo-surface” of standard heterogeneous metal oxide
supports such as silica and alumina. The relatively acidic
phenolic hydroxy groups are only marginally less acidic than
(1) (a) Verkerk, U. H.; Fujita, M.; Dzwiniel, T. L.; McDonald, R.;
Stryker, J. M. J. Am. Chem. Soc. 2002, 124, 9988–9989. (b) Fujita, M.; Qi,
G.; Verkerk, U. H.; Dzwiniel, T. L.; McDonald, R.; Stryker, J. M. Org.
Lett. 2004, 6, 2653–2656. Improved synthesis: (c) Chung, M.-K.; Qi, G.;
Stryker, J. M. Org. Lett. 2006, 8, 1491–1494. (d) Chung, M.-K.; Fancy, P.;
Stryker, J. M. Can. J. Chem. 2006, 84, 1250–1253.
(2) Gutsche, C. D. Calixarenes ReVisited; Royal Society of Chemistry:
Cambridge, England, 1998, and references therein.
(3) Mislow, K. Acc. Chem. Res. 1976, 9, 26–33, and references therein.
(4) (a) Floriani, C. Chem.-Eur. J. 1999, 5, 19–23. and references therein.
(b) Giannini, L.; Guillemot, G.; Solari, E.; Floriani, C.; Re, N.; Chiesi-
Villa, A.; Rizzoli, C. J. Am. Chem. Soc. 1999, 121, 2797–2807.
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2008 American Chemical Society

many surface silanol residues, and the rotational flexibility
allows for the accommodation of a range of main group and
transition metal elements.
2 proceeds under conventional conditions,11,12 giving tet-
rakis(3-bromo-5-tert-butyl-2-methoxyphenyl)ethene 3 or tet-
rakis(3-bromo-5-tert-butyl-2-hydroxyphenyl)ethene 4, re-
spectively, cleanly and in high yield (Scheme 1). Despite
For applications to catalysis, steric isolation of the binding
sites is essential to directing metal coordination, inhibiting
intermolecular aggregation, and the formation of sandwich
structures lacking surface-like character.5 To this point,
however, the largest substituent that has been successfully
installed adjacent to the hydroxy functionality is the n-propyl
group, which was introduced by a 4-fold Claisen rearrange-
ment of tetrakis(2-allyloxyphenyl)ethene followed by stan-
dard catalytic hydrogenation.1a While this classical procedure
is highly efficient (>80% overall starting from the unsub-
stituted ligand), the introduction of sterically larger ortho-
substituents with equal efficiency represents a substantial
synthetic challenge.6
Scheme 1
In this communication, we report the use of the retro-
Brook rearrangement7 for the simultaneous installation of
four trialkylsilyl or aryldialkylsilyl substituents onto the
tetrakis(2-hydroxphenyl)ethene ligand framework. Under
optimized conditions, this intramolecular 1,3-migration reac-
tion can be conducted on a substantial scale and proceeds in
remarkably high yields. The resulting tetrakis(2-hydroxy-3-
silylphenyl)ethene derivatives have been characterized both
spectroscopically and, for the trimethylsilyl derivative, by
X-ray crystallography.8
Application of the retro-Brook rearrangement to the
tetrakis(2-hydroxphenyl)ethene structural class requires ef-
ficient halogenation ortho to the phenoxy residues. To avoid
issues of regioselectivity,9 the synthesis begins with deriva-
tives bearing 5-tert-butyl substituents in each arene
residue.1a,c These compounds are prepared in high yield on
a multigram scale via the McMurry olefination of bis(5-tert-
butyl-2-methoxyphenyl)methanone.1c,10
the dense functionality, NMR spectroscopic analysis at room
temperature reveals no evidence of restricted rotation in either
system.
The retro-Brook sequence is initiated by exhaustive
O-silylation (Scheme 2). For sterically small silyl derivatives,
Scheme 2
Bromination of either tetrakis(5-tert-butyl-2-methoxyphe-
nyl)ethene 1 or tetrakis(5-tert-butyl-2-hydroxyphenyl)ethene
(5) Verkerk, U. H.; McDonald, R.; Stryker, J. M. Can. J. Chem. 2005,
83, 922–928.
(6) The introduction of tert-butyl substituents to either tetrakis(2-
hydroxyphenyl)ethene or tetrakis(5-tert-butyl-2-hydroxyphenyl)ethene via
Friedel-Crafts alkylation using a range of standard synthetic procedures
invariably produces intractable mixtures of tert-butylated products and
cannot be driven to completion.
(7) (a) Brook, A. G. Acc. Chem. Res. 1974, 7, 77–83. (b) Wright, A.;
West, R. J. Am. Chem. Soc. 1974, 96, 3214–3222, and 3227-3232. (c)
Linderman, R. J.; Ghannam, A. J. Am. Chem. Soc. 1990, 112, 2392–2398.
Review: (d) Moser, W. H. Tetrahedron 2001, 57, 2065-2084. Phenolic
cases: (e) Simchen, G.; Pfetschinger, J. Angew. Chem., Int. Ed. Engl. 1976,
15, 428–429. (f) Billedeau, R. J.; Sibi, M. P.; Snieckus, V. Teterahedron
Lett. 1983, 24, 4515–4518. (g) Maruoka, K.; Itoh, T.; Araki, Y.; Shirasaka,
T.; Yamamoto, H. Bull. Soc. Chem. Jpn. 1988, 61, 2975–2976. (h) Thadani,
A. N.; Huang, Y.; Rawal, V. H. Org. Lett. 2007, 9, 3873–3876.
(8) Detailed experimental procedures and complete characterization data
are provided as Supporting Information.
(9) None of the methodologies reported for selective ortho-bromination
of 4-unsubstituted phenols was sufficiently selective for adaptation to this
substrate. See, for example: (a) Posner, G. H.; Canella, K. A. J. Am. Chem.
Soc. 1985, 107, 2571–2573. (b) Beak, P.; Brown, R. A. J. Org. Chem. 1977,
42, 1823–1824.
the simple chlorosilane is sufficiently reactive to provide
quantitative conversion. Reactions using the more hindered
silyl derivatives, however, require the use of the correspond-
ing silyl triflate reagents for optimal conversion.13 The
(10) Chung, M.-K.; Stryker, J. M. Inorg. Synth., in press
.
(11) Majetich, G.; Hicks, R.; Reister, S. J. Org. Chem. 1997, 62, 4321–
4326
.
(12) (a) Despite a previous report,12b the bromination of 2 using a Br2/
DMSO reagent was neither clean nor reproducible upon scale-up. In
addition, a procedure reported for the bromination of 1 was not adaptable
(13) (a) BuMe2SiOTf: Corey, E. J.; Cho, H.; Rucker, C.; Hua, D.-H.
t
Tetrahedron Lett. 1981, 22, 3455–3458. (b) iPrMe2SiOTf: Olah, G. A.; Laali,
K.; Farooq, O. Organometallics 1984, 3, 1337-1340. (c) Ph2MeSiOTf;
Uhlig, W. J. Organomet. Chem. 1993, 452, 29–32.
to large scale. (b) Verkerk, U. Ph.D Dissertation, 2002
.
3826
Org. Lett., Vol. 10, No. 17, 2008

intermediate silyloxy derivatives 5a-c, homogeneous by
analytical TLC analysis, were isolated by filtration through
a short column of silica gel but not further purified or
characterized.
Scheme 3
Metalation of the silyloxy compounds 5a-c with n-BuLi
at low temperature initiates the 4-fold retro-Brook rearrange-
ment, providing the corresponding tetrakis(5-tert-butyl-2-
hydroxy-3-silylphenyl)ethenes 6a-c in excellent overall
yield. The ortho-silylated compounds were obtained as
amorphous white solids after isolation and purification by
chromatography on silica gel. Despite the markedly increased
steric bulk, the silyl derivatives showed no evidence for
restricted rotation at room temperature by NMR spectros-
copy. At low temperature, however, 1H NMR spectroscopy
of 6a (-60 °C, toluene-d8) revealed a complex mixture of
static rotational isomers but no obvious energetic bias toward
any one conformation.
Although resistant to crystallization, single crystals of the
trimethylsilyl derivative 6a were obtained as colorless blocks
by slowly cooling a hot benzene solution. The solid state
structure was determined by X-ray crystallography (Figure
1),8 revealing a conformational preference for the rotational
is conducted under relatively mild conditions (Scheme 3).
After deprotonating the remaining free phenolic residues
using a nonmetallating base (KH or MeMgCl), the retro-
Brook rearrangement at the silylated sites is triggered by the
addition of n-BuLi (2 equiv) at low temperature, followed
by a water quench. Without purification, the partial silylation/
migration protocol is then repeated, providing the ortho-
silylated products 6d,e in very reasonable overall yields.
Under these conditions, the intial double metal/halogen
exchange reaction is highly selective for the silyloxy sites,
leaving intact the arylbromide functionality adjacent to the
remaining alkoxide residues. The “preemptive” deprotonation
of the nonsilylated phenols is a precautionary measure
designed to avoid competitive metalation and destructive
protonation at nonsilylated phenolic residues. This step
provides only a marginal improvement in the yield of the
tert-butyldimethylsilyl derivative 6d but raises substantially
the yield of the methyldiphenylsilylated product 6e. This
suggests that only in the latter case does the metal/halogen
exchange reaction become competitive with the deprotona-
tion of unsilylated phenols, leading to some nonproductive
quenching of metallated intermediates.
Figure 1. Solid state molecular structure of tetrakis(5-tert-butyl-
2-hydroxy-3-trimethylsilylphenyl)ethene 6a. All hydrogen atoms
have been omitted for clarity. Thermal ellipsoids are shown at the
20% probability level. Nonbonding distance between O1A and
O2A: 5.560 Å. Final residuals: R1 ) 0.0586. wR2 ) 0.1741.
isomer that places the two hydroxy groups from mutually
trans-phenolic residues on opposite faces of the ethylene
plane. In contrast to the unsubstituted tetrakis(2-
hydroxyphenyl)ethene,1a neither intramolecular nor inter-
molecular hydrogen bonding is observed for the sterically
isolated functionality. In the absence of self-association, the
observed solid state conformation is, presumably, that which
minimizes the net molecular dipole for the system.
Perhaps unsurprisingly, exhaustive O-silylation is prob-
lematic for sterically larger silanes. After considerable
optimization, however, an iterative protocol has been devel-
oped that allows for the efficient preparation of tetrakis(ortho-
silylated) compounds bearing very large silyl functionalities.
In this procedure, an initial nonspecific bis(silylation) reaction
It is equally noteworthy that the second iteration of the
silylation is highly selective for the remaining bromide-
bearing residues: no evidence for competitive silylation of
the presumably more sterically encumbered ortho-silylated
phenols is observed. The attenuated yield obtained for the
methyldiphenylsilyl derivative can be tentatively ascribed to
the reversible nature of the retro-Brook rearrangement for
electron-deficient silanes,7d suggesting a natural electronic
limit to the scope of this methodology.
The extension of the ortho-silylation protocol to partial
substitution of the ligand periphery addresses the synthesis
of differentially functionalized derivatives, which further
enhances the potential for applications development. To this
end, we report that the silylation of tetrakis(3-bromo-5-tert-
Org. Lett., Vol. 10, No. 17, 2008
3827

butyl-2-hydroxyphenyl)ethene 4 in the presence of excess
hexamethyldisilazane14 proceeds selectively to the tris(tri-
methylsilylated) derivative. Without purification, treatment
of this intermediate with excess n-BuLi leads to the isolation
of the tristrimethylsilylated product 7 (81%), accompanied
by a minor amount of tetrakis(5-tert-butyl-2-hydroxy-3-
trimethylsilylphenyl)ethene 6a (6%) (eq 1). Further inves-
tigation of selective partial silylation reactions is in progress.
polydentate ligand system in catalysis and supramolecular
chemistry. The use of this soluble platform to model the
coordination chemistry and catalytic reactions mediated by
polymetallic arrays coordinated to heterogeneous supports
will be reported in due course.
Acknowledgment. We thank the NSERC-CRO/SRO
program for financial support and M. J. Ferguson of the
University of Alberta Structure Determination Laboratory
for X-ray crystallography. M.K.C. gratefully acknowledges
Alberta Ingenuity and the Killam Trusts for postdoctoral
fellowships.
Supporting Information Available: Experimental pro-
cedures and complete characterization data for all new
compounds and details of the X-ray crystallography for
compound 6a. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL801427W
The high efficiency of this ortho-silylation protocol offers
(14) Gautret, P.; El-Ghammarti, S.; Legrand, A.; Couturier, D.; Rigo,
considerable promise for developing applications of this
B. Synth. Commun. 1996, 26, 707–713.
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