Toward Covalently Linked Organic Networks: Model Studies and Connector Syntheses

Article abstract of DOI:10.1021/jo9714167

A model 1-naphthoic acid bearing a peri-positioned cinnamic acid residue crystallizes as a closed H-bonded dimer. Irradiation of this crystalline solid provides an α-truxillate-type cyclobutane photodimer in quantitative yield. Further synthesis studies h

Full text of DOI:10.1021/jo9714167

8814
J . Org. Chem. 1997, 62, 8814-8820
Tow a r d Cova len tly Lin k ed Or ga n ic Netw or k s: Mod el Stu d ies a n d
Con n ector Syn th eses
Ken S. Feldman,* Robert F. Campbell, J oe C. Saunders, Chuljin Ahn, and
Katherine M. Masters
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802
Received J uly 31, 1997X
A model 1-naphthoic acid bearing a peri-positioned cinnamic acid residue crystallizes as a closed
H-bonded dimer. Irradiation of this crystalline solid provides an R-truxillate-type cyclobutane
photodimer in quantitative yield. Further synthesis studies have led to more highly functionalized
naphthoic/cinnamic acid species capable of (pseudo)centrosymmetric attachment to polyvalent hubs.
This system demonstrates the feasibility of designing a covalent molecular connector whose
orientation is encoded by its H-bonding pattern.
The organization of functional monomers into periodic
on either “shot gun” polymerization of directional, poly-
valent monomers4 or complementary “bottom-up” strate-
gies that utilize iterative synthesis have been described.5
A third approach currently under development builds
upon H-bond-directed monomer assembly for ultimate
delivery of covalently linked periodic higher dimensional
arrays.8 Specifically, a two-stage protocol that utilizes
(1) monomer preorganization and preorientation in a
periodic network by H-bonded encoded crystallization and
(2) in situ covalent cross-linking of these monomers in
their lattice positions offers the possibility of delibera-
tively converting molecules into materials of designed
architecture. This strategy takes advantage of the self-
correcting nature of a kinetically labile but (at least
locally) thermodynamically driven crystallization process
to bring reactive entities within bonding proximity in the
solid state. The critical challenge, then, is to design
molecular connectors that (1) have self-complementary
H-bonding arrays, (2) bear appropriate reactive function-
ality poised for intermolecular covalent bond formation
only after the H-bond network is in place, and (3) suffer
only minimal geometric distortion upon conversion of the
H-bond connection to a covalent connection. The design
and synthesis of one such connector unit is described
herein.
higher dimensional arrays remains an enduring chal-
lenge in materials research. Self-ordering strategies for
polyvalent monomers that encode the assembly instruc-
tions with either H-bonding1 or metal ligation2 have led
to major advances in the preparation of two- and three-
dimensional networks of defined and largely predictable
architecture. However, the kinetic lability of most of
these noncovalent attachments, coupled with the rela-
tively modest connection enthalpies (metal-ligand; ∆Hf
e -10 kcal/mol,3a carboxylic acid dimerization; ∆Hf ∼
-14 kcal/mol (gas phase),3b pyridone dimerization; ∆Hf
) -5.4 kcal/mol3c) render them characteristically fragile
and susceptible to collapse upon solvent removal. Many
downstream applications of these “designer solids” (e.g.,
shape-selective separations, catalysis) might require a
more robust framework than can be delivered by these
approaches to monomer connection.
Some of these inherent deficiencies might be overcome
by synthesis of a kinetically inert, completely covalently
linked periodic network, wherein the connection enthal-
pies exceed H-bonding and metal ligation by substantial
margins. Strategies directed toward this goal are still
at the formative stages. Promising approaches that rely
The peri cinnamic acid-substituted naphthoic acid
derivate 1 is a plausible candidate for this molecular
connector (Scheme 1). When attached to a hub as shown,
the well-defined J -shaped geometry bearing two H-
bonding termini suggests that a self-complementary
H-bond-mediated dimerization will afford a linear con-
nection between two hubs, 2. The choice of a peri-
substituted naphthalene spacer ensures that the cin-
namic acid alkene moieties reside within the empirically
determined window (e4.2 Å) for successful solid-state
photochemical [2π + 2π] cycloaddition.6 Topochemical
dimerization of a crystalline sample of 2 upon irradiation
should then afford the cyclobutane product 3, in which
the two connector modules are now covalently cross-
linked. Successful execution of this plan can provide a
paradigm for replacing directional but weak intermo-
lecular association with more robust covalent linkages.
X Abstract published in Advance ACS Abstracts, November 15, 1997.
(1) Leading references can be found in: (a) Zaworotko, M. J . Chem.
Soc. Rev. 1994, 283. (b) Ermer, O. J . Am. Chem. Soc. 1988, 110, 3747.
(c) Wang, K.; Simard, M.; and Wuest, J . D. J . Am. Chem. Soc. 1994,
116, 12119. (d) Brunet, P.; Simard, M.; Wuest, J . D. J . Am. Chem.
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M. J .; Hoskins, B. F.; Robson, R.; Williams, G. A. J . Am. Chem. Soc.
1992, 114, 10641. (b) Hoskins, B. F.; Robson, R. J . Am. Chem. Soc.
1989, 111, 5963. (c) Yaghi, O. M.; Li, H. J . Am. Chem. Soc. 1996, 118,
295.
(3) (a) Christensen, J . J .; Izatt, R. M. Handbook of Metal Ligand
Heats and Related Thermodynamic Quantities; Marcel Dekker: New
York, 1983. (b) J oesten, M. D.; Schaad, L. J . Hydrogen Bonding; Marcel
Dekker: New York, 1974; pp 287-288. (c) Hammes, G. G.; Park, A.
C. J . Am. Chem. Soc. 1969, 91, 956.
(4) Leading references can be found in: (a) Rubin, Y.; Knobler, C.
B.; Diederich, F. Angew. Chem., Int. Ed. Engl. 1991, 30, 698. (b)
Neenan, T. X.; Whitesides, G. M. J . Org. Chem. 1988 53, 2489. (c)
Feldman, K. S.; Mareska, D. A.; Weinreb, C. K.; Chasmawala, M. J .
Chem. Soc., Chem. Commun. 1996, 865. (d) Vaid, T. P.; Lobkovsky, E.
B.; Wolczanski, P. T. J . Am. Chem. Soc. 1997, 119, 8742.
(5) Leading references can be found in: a) Xu, Z.; Moore, J . S. Angew.
Chem., Int. Ed. Engl. 1993, 32, 1354. (b) Young, J . K.; Nelson, J . C.;
Moore, J . S. J . Am. Chem. Soc. 1994, 116, 10841. (c) Boldi, A. M.;
Anthony, J .; Gramlich, V.; Knobler, C. B.; Boudon, C.; Gisselbrecht,
J .-P.; Gross, M.; Diederich, F. Helv. Chim. Acta 1995, 87, 779. (d) J ones,
L.; Schumm, J . S.; Tour, J . M. J . Org. Chem. 1997, 62, 1388.
(6) Leading references can be found in: (a) Schmidt, G. M. Pure
Appl. Chem. 1971, 27, 647. (b) Savion, Z.; Wernick, D. L. J . Org. Chem.
1993, 58, 2424. (c) Enkelmann, V.; Wegner, G.; Novak, K.; Wagener,
K. B. J . Am. Chem. Soc. 1993, 115, 10390.
(7) All molecular mechanics modeling was performed on a Silicon
Graphics Power Indigo 2XZ computer with Macromodel 5.5 (mm3*
force field). Conformational space about rotatable bonds was searched
with
a directed 1000-step Monte Carlo algorithm. Mohamadi, F.;
Richards, N. G. J .; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield,
C.; Chang, G.; Hendrickson, T.; Still, W. C. J . Comput. Chem. 1990,
11, 440.
(8) Feldman, K. S.; Campbell, R. F. J . Org. Chem. 1995, 60, 1924.
S0022-3263(97)01416-3 CCC: $14.00 © 1997 American Chemical Society

Toward Covalently Linked Organic Networks
J . Org. Chem., Vol. 62, No. 25, 1997 8815
Sch em e 1
Sch em e 2
Maintaining congruence between core atoms of the
initial H-bonded connectors and the derived covalently
linked species may be critical for sustaining lattice
superstructure upon photodimerization. Hence, the con-
sequences of the structural deformations that accompany
the cycloaddition-induced decrease of the alkene-alkene
gap from ca. 3.62 Å to ca. 1.54 Å on the H-bonded
network’s integrity are an area of concern. Molecular
mechanics calculations7 on R-cinnamic acid photodimer-
ization in support of crystallographic studies by Enkel-
mann et al.6c give some sense of the magnitude of
molecular motion, which results from the tradeoff be-
tween accrued strain energy and crystal packing forces.
Crystalline R-trans-cinnamic acid 4 photodimerizes upon
tailing irradiation to furnish the cyclobutane 5, eq 1.
this example, and the “hubs” (e.g., phenyl rings) rotate
but do not otherwise suffer significant dislocation.
A preliminary report describing the successful realiza-
tion of this two-stage covalent connection strategy in a
model system has been disclosed.8 Full synthesis details
and analysis of this model system are provided below.
In addition, the design and preparation of a cinnamyl/
naphthoic acid derivative that is suitable for attachment
to multivalent hubs is detailed. Taken together, these
advances provide the foundation for studies directed
toward the preparation of two- and three-dimensional
covalently linked organic networks.
Resu lts a n d Discu ssion
The model naphthoic acid/cinnamic acid 17 (Scheme
3) was chosen to test the feasibility of the two-stage
crystallization/cross-linking strategy outlined above. This
simple species has no functionality to permit attachment
with central hub modules. Syntheses of more complex
connectors with appropriate (electrophilic) moieties for
fastening to polyvalent (nucleophilic) hubs will follow
successful execution of the model system chemistry.
The initial route to model diacid 17 commenced with
the known iodo methyl ester 6,9 available from naphthoic
anhydride in three steps (Scheme 2). Initial attempts
to effect a mixed Ullmann coupling with cinnamyl
bromide 7 afforded mainly the known binaphthyl ester
810 with only a trace (<5%) of the desired product 9.
Biaryl aldehyde 11 was obtained, however, via Suzuki
coupling12 of the known boronic acid 1011 with iodide 6,
followed by Emmons-Horner homologation. The diester
9 proved resistant to complete hydrolysis. Basic treat-
ment led to attack at only the cinnamyl ester unit with
much attendant decomposition. Attempted Sn2-type
ester cleavage was equally unsuccessful, with the results
(decomposition or no reaction) varying as per the harsh-
Molecular mechanics calculations on 5, in which the
phenyl ipso carbons and carbonyl carbons are “locked”
at their initial precyclcoaddition distances, and also on
an unconstrained version of this dimer, 5a , reveal that
an incremental strain of ca. 5.0 kcal/mol accompanies
photodimerization without relaxation. Enkelmann has
documented that this strain increment apparently can
be accommodated in the cinnamic acid lattice without
disruptive consequences, as X-ray analysis of the crystal
undergoing photodimerization reveals that the carbons
noted above do not change position (relax) within experi-
mental limits through 67% conversion. Thus, the com-
petition between crystal packing forces and strain re-
sulting from bond angle distortion favors the former in
(9) Bailey, R. J .; Card, P. J .; Shechter, H. J . Am. Chem. Soc. 1983,
105, 6096.
(10) Hall, D. M.; Ridgwell, S.; Turner, E. E. J . Chem. Soc. 1954,
2498.
(11) Torssell, K. Arkiv. Kemi 1956, 10, 507.
(12) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11,
513.

8816 J . Org. Chem., Vol. 62, No. 25, 1997
Feldman et al.
Sch em e 3
Sch em e 4
ness of the conditions. Interestingly, treatment of diester
9 with BBr3 produced the tetracycle 12 resulting, pre-
sumably, from internal Friedel-Crafts acylation of an
intermediate acyl bromide. Eventually, this dimethyl
ester chemistry was abandoned in favor of a related route
featuring a more labile protecting group.
The trichloroethyl protecting group appeared to offer
advantages in both synthesis and removal for this
sterically hindered and nucleophile-sensitive system, and
so diester 16 was substituted as a target. The chemistry
proceeded as described above from known iodo acid 139
without event (Scheme 3). Deprotection of diester 16
with Zn/HOAc/THF afforded the desired diacid 17 in good
yield and free of impurities.
Initial attempts to obtain a suitable sample of 17 for
X-ray analysis by crystallization from various solvent
mixtures were invariably frustrated by deposition of
small and irregular crystals (<0.1 mm largest dimen-
sion). However, this deficiency was corrected by inclusion
of a small amount of CH3OH in the otherwise nonprotic
solvent (mixtures of hexane/THF or heptane/DME), and
well-formed rods (∼1 mm × 3 mm) were deposited over
several days at 4 °C.13 In any event, X-ray analysis of
crystals of 17 grown from heptane/DME/CH3OH revealed
that the design criteria represented by structure 2 were
met.8 Diacid 17 crystallized as a closed dimer () 18) with
one molecule of DME per diacid pair. The entire dimer
unit spans 19 Å, and these units stack in a herringbone-
type pattern in the crystal with no discernible H-bonding
interactions between discrete pairs. An examination of
the structural details of 18 reveals the mimicry between
the aryl ring and the carboxylic acid H-bonded dimer,
which underlies the design strategy. These distances are
incommensurate (2.85 vs 3.83 Å, respectively), and hence,
the alkene moieties are shifted slightly out of register.
Nevertheless, the critical alkene-alkene distance in this
dimer (3.62 Å) is well within the margin for expected
photocycloaddition.
Irradiation of crystalline 17 () dimer 18), including
samples taken from the same batch that provided the
single crystal for X-ray analysis, in a Rayonet photo-
reactor (300 nm) under ambient conditions for ∼45 h led
to complete consumption of starting material, Scheme 4.
The resulting solid was dissolved in CH2Cl2 and meth-
ylated (CH2N2) for characterization purposes. The 1H
and 13C NMR spectral data of the tetraester 20 were
consistent with a single, highly symmetrical cyclobutyl
photodimer, but a distinction between the four possible
isomers (R-truxillate, δ-truxinate, â-truxinate, and ꢀ-trux-
illate) could not be made. The four isomers noted above
for the methyl cinnamate photodimerization series were
prepared by literature procedures to facilitate indepen-
dent stereochemical and regiochemical assignment of
20.14 In addition, further naphthoate/cinnamate isomeric
photodimers were prepared by irradiation of a dilute
benzene solution of dimethyl ester 9 at 300 nm, Scheme
4. Control experiments indicated that the diacid 17 did
not afford any cyclobutyl-containing products upon ex-
tended irradiation in THF solution, nor did crystalline
diester 9 yield any photodimers when irradiated as per
solid 17. Examination of the diagnostic methine region
in the 1H NMR spectra for 20-22 in comparison with
the four known simpler diphenyl cyclobutyl analogues
prepared from cinnamate permitted unamibguous struc-
tural assignment (see the Supporting Information for
1
copies of the relevant H NMR spectra). Thus, the diacid
17 does in fact photodimerize through the closed H-
bonded pair to furnish the R-truxillate stereo- and
regioisomer 19. Unfortunately direct confirmation of this
conclusion was not possible, as the irradiated crystals of
18 were not suitable for X-ray analysis.
The efficiency of this photodimerization (approaching
100%) is worthy of note. In contrast, a limiting yield
(∼86%) for photodimerization of R-cinnamic acid has been
calculated via a theoretical independent-site model.6b The
unique H-bonding opportunities available to 17 render
this model invalid, and the dependent-site photodimer-
ization of 17 is not so constrained.
These encouraging results prompted design of a more
advanced molecular connector with hub-attachment ca-
pabilities. This new connector would have to meet two
specific criteria for success: (1) preservation of the
(14) (a) R-Truxillic and â-truxinic acids: Cohen, M. D.; Schmidt, G.
M.; Sonntag, F. I. J . Chem. Soc. 1964, 2000. (b) ꢀ-Truxillic acid:
Stoermer, R.; Emmel, E. Chem. Ber. 1920, 53, 7. (c) δ-Truxinic acid:
Freedman, M.; Mohadger, Y.; Rennert, J .; Soloway, S.; Waltcher, I.
Org. Prep. Proc. 1969, 267.
(13) Zerkowski, J . A.; MacDonald, J . C.; Seto, C. T.; Wierda, D. A.;
Whitesides, G. M. J . Am. Chem. Soc. 1994, 116, 2382 and references
therein.

Toward Covalently Linked Organic Networks
J . Org. Chem., Vol. 62, No. 25, 1997 8817
Sch em e 5
coupling partners were available from 4-(tri-n-butylstan-
nyl)benzaldehyde16 and the appropriate Emmons-Hor-
ner reagent.17 Stille coupling was superior to the Suzuki
procedure in both the anhydride series (28a f 31, 64%)
and in the model naphthylene series (cf. Scheme 2, 6 +
29a f 9, 52%). In any event, these concise routes provide
the desired naphthyl cinnamyl anhydrides in five steps
from acenaphthene on a gram scale.
In summary, the feasibility of designing a molecular
connector that utilizes labile H-bonds to orient reactive
functionality for subsequent covalent attachment in the
solid state has been demonstrated. Extension of this
chemistry to the two- and three-dimensional polymeri-
zation of tri- and tetravalent monomers, respectively, will
require the availability of bifunctional connectors capable
of both directional H-bonding and covalent linkage to
central polyvalent hub units. Naphthalene-based anhy-
dride diesters that might serve in this capacity have been
prepared. Hub attachment, deprotection, and crystal-
lization/cross-linking studies are ongoing with these
species.
Exp er im en ta l Section
Tetrahydrofuran (THF) and diethyl ether (Et2O) were
purified by distillation from sodium/benzophenone under Ar
immediately before use. Moisture- and oxygen-sensitive reac-
tions were carried out in flame-dried glassware under Ar.
Solvents for chromatography (Et2O, EtOAc, CH2Cl2, hexane)
were distilled from CaH2 prior to use. Flash column chroma-
tography was carried out under positive pressure using 32-
63 µm silica gel and the indicated solvents.18 Melting points
are uncorrected. Chemical impact mass spectra (CIMS) were
obtained with isobutane as the reagent gas, and electron
impact mass spectra (EIMS) were obtained at 50-70 eV. FAB
high-resolution mass spectra were obtained from the mass
spectrometry laboratory at the University of Texas at Austin.
Combustion analyses were performed by either Galbraith
Laboratories, Knoxville, TN, or Midwest Microlab, Indianapo-
lis, IN. 1H and 13C NMR spectra are provided in the Support-
ing Information to establish purity for those compounds that
were not subject to combustion analyses.
attachment linearity implicit in Scheme 1 and (2) facile
and high yielding hub-to-naphthalene bond formation.
The anhydride 24 appeared to satisfy these requirements,
as dehydrative condensation with primary amine-bearing
hubs 23 should furnish polyimide-tipped multivalent
monomers ready for ester deprotection and then crystal-
lization/photo-cross-linking, eq 2.
Dim eth yl (E)-8-[4-(2-P r op en oyl)p h en yl]-1-n a p h ylen e-
ca r boxyla te (9). Methyl 8-iodo-1-naphthylenecarboxylate (6)9
(377 mg, 1.2 mmol), boronic acid 1011 (200 mg, 1.33 mmol, 1.1
equiv), and tetrakis(triphenylphosphine)palladium (46 mg,
0.04 mmol, 0.03 equiv) in 10 mL of benzene, 5 mL of 1 M K2-
CO3, and 2 mL of EtOH were purged with Ar, heated to reflux
under Ar, and maintained there for 45 h. At that time, TLC
indicated that iodide 6 had been nearly totally consumed. The
reaction solution was cooled to room temperature, poured into
an equal volume of water, and extracted with 2 × 20 mL of
Et2O. The combined organic phases were washed with brine,
dried over Na2SO4, filtered, and concentrated in vacuo, and
the residue was purified by flash chromatography on silica gel
(20% Et2O/hexane as eluent) to yield 274 mg of methyl 8-(4-
formylphenyl)-1-naphthylenecarboxylate (11) (79%) following
flash chromatography on silica gel with 30% Et2O/hexane as
eluent: IR (CCl4) 1727, 1706 cm-1; 1H NMR (200 MHz, CDCl3)
δ 10.05 (s, 1 H), 7.99 (dd, J ) 8.2, 1.4 Hz, 1 H), 7.9 (m, 3 H),
7.75 (dd, J ) 5.7, 1.6 Hz, 1 H), 7.5 (m, 5 H), 3.09 (s, 3 H); 13C
NMR (50 MHz, CDCl3) δ 191.9, 169.8, 149.2, 138.1, 134.9,
134.7, 132.1, 130.7, 130.6, 129.8, 129.5, 129.4, 129.2, 129.1,
125.9, 125.0, 51.5; MS m/z (relative intensity) 290 (M+, 100),
231 (55). A sample of this aldehyde (400 mg, 1.38 mmol) in 5
The choice of protecting group R in 24 again will play
an important role in the outcome of this chemistry.
Initial synthesis efforts were directed toward two can-
didates, CH2CCl3 and CH2CH2TMS (Scheme 5). Both of
these species utilize requisite nonnucleophilic deprotec-
tion protocols to unveil their derived acids. However,
competition for the nucleophilic primary amines of 23
between the unsaturated cinnamyl ester unit in 24 and
the relatively unreactive anhydride moiety is a source of
concern, especially in the more electrophilic trichloroethyl
ester series.
Synthesis of both diesters 30a and 30b began with the
known bromo acid 2615 available in two steps from
acenaphthene (Scheme 5). Conversion of 26 into the
bromo esters 27a /27b proceeded without event and set
the stage for the key reaction in this sequence, oxidation
of the ethylene bridge. Chromic acid oxidation of 27a
and 27b did indeed deliver the desired anhydrides 28a
and 29a , respectively, with no evidence for destruction
of the ester moieties. Similar oxidation of bromo acid
26 did not furnish the expected anhydride product. The
intact cinnamyl ester unit was attached to the bromides
28a and 28b via Stille coupling with the stannylcin-
namates 29a and 29b, respectively. Both of these
(15) Letsinger, R. L.; Gilpin, J . A.; Vullo, W. J . J . Org. Chem. 1962,
27, 672.
(16) Sessler, J . L.; Wang, B.; Harriman, A. J . Am. Chem. Soc. 1993,
115, 10418.
(17) (a) 15: Clayton, J . P.; Luk, K.; Rogers, N. H. J . Chem. Soc.,
Perkin Trans. 1 1979, 312. (b) 2-(Trimethylsilyl)ethyl diethylphos-
phonoacetate: Taylor, E. C.; Davies, H. M. L. J . Org. Chem. 1986, 51,
1537.
(18) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.

8818 J . Org. Chem., Vol. 62, No. 25, 1997
Feldman et al.
mL of dry DMF was added dropwise to a stirring suspension
of sodium trimethylphosphonoacetate (from 66 mg of 60%
NaH, degreased (1.66 mol, 1.2 equiv) and 268 µL of trimethyl
phosphonoacetate (1.66 mmol, 1.2 equiv) in 10 mL of dry DMF
at 0 °C. The solution was warmed to rt and stirred there until
TLC analysis indicated complete consumption of starting
aldehyde. The reaction solution was poured into an equal
volume of ice-cold 1 M H3PO4. This aqueous solution was
extracted with 2 × 10 mL of Et2O, the combined organic phases
were washed with saturated brine, dried over Na2SO4, filtered,
and concentrated in vacuo, and the residue was purified by
flash column chromatography (silica gel, 30% Et2O/hexane) to
furnish 401 mg (84%) of diester 9 as a light yellow solid.
Recrystallization from 3:1 Et2O/hexane afforded 330 mg of the
EtOH. This heterogeneous mixture was purged with Ar,
heated to reflux under Ar, and maintained there for 45 h. At
that time, TLC indicated that bromide 13b had been nearly
totally consumed. The reaction solution was cooled to rt,
poured into an equal volume of water, and extracted with 2 ×
20 mL of Et2O. The combined organic phases were washed
with brine, dried over Na2SO4, filtered, and concentrated in
vacuo, and the residue was purified by the flash chromatog-
raphy on silica gel (20% Et2O/hexane as eluent) to yield 309
mg of aldehyde 14 as a white solid (52%). A sample for
elemental analysis was prepared by vapor diffusion crystal-
lization with THF/hexane: mp 130-132 °C; IR (CCl4) 1743,
1
1701 cm-1; H NMR (360 MHz, CDCl3) δ 10.09 (s, 1 H), 8.09
(dd, J ) 8.2, 1.3 Hz, 1 H), 7.96 (d, J ) 8.1 Hz, 2 H), 7.9 (m, 1
H), 7.89 (dd, J ) 7.1, 1.3 Hz, 1H), 7.6 (m, 5H), 4.17 (s, 2 H);
13C NMR (90 MHz, CDCl3) δ 191.7, 166.9, 149.1, 138.0, 135.0,
134.8, 132.8, 130.8, 129.9, 129.8, 129.4, 129.14, 129.08, 127.9,
126.2, 125.0, 94.6, 74.0; MS m/z (relative intensity) 408 (M+,
14), 406 (13), 231 (78). Anal. Calcd for C20H13Cl3O3: C, 58.89;
H, 3.21; Cl, 26.61. Found: C, 58.90; H, 3.19; Cl 27.10.
2,2,2-Tr ich lor oeth yl (E)-8-[4-[[(2,2,2-Tr ich lor oeth oxy)-
car bon yl]eth en yl]ph en yl]-1-n aph th ylen ecar boxylate (16).
2,2,2-Trichloroethyl diethoxyphosphonoacetate (15)17 (145 mg,
0.44 mmol, 1.2 equiv) was added dropwise to a stirring
suspension of degreased NaH (60% suspension in oil, 189 mg,
0.44 mmol, 1.2 equiv) in 1 mL of dry DMF. After gas evolution
had ceased, solid aldehyde 14 (150 mg, 0.37 mmol) was added
in one portion, resulting in a homogeneous, light orange
solution. After 30 min, TLC indicated consumption of starting
aldehyde, and so the reaction solution was poured into an
equal volume of ice-cold 1 M H3PO4. This aqueous solution
was extracted with 2 × 10 mL of Et2O, the combined organic
phases were washed with saturated brine, dried over Na2SO4,
filtered, concentrated in vacuo, and the white solid residue was
purified by crystallization from 20% Et2O in hexane to furnish
170 mg of diester 16 as a white powdery solid (79%). A sample
for elemental analysis was prepared by vapor diffusion crys-
tallization from THF/hexane: mp 181-182 °C; IR (CCl4) 1740
diester as white crystals: mp 108-110 °C; IR (CCl4) 1725 cm-1
;
1H NMR (200 MHz, CDCl3) δ 7.96 (dd, J ) 8.3, 1.4 Hz, 1 H),
7.85 (dd, J ) 7.9, 1.5 Hz, 1 H), 7.74 (d, J ) 15.9 Hz, 1 H), 7.73
(m, 1 H), 7.75 (m, 7H), 6.48 (d, J ) 16.0 Hz, 1 H), 3.79 (s, 3
H), 3.09 (s, 3 H); 13C NMR (50 MHz, CDCl3) δ 169.9, 167.3,
144.9, 144.2, 138.6, 134.7, 132.9, 131.9, 130.9, 130.3, 129.1,
129.0, 128.5, 128.0, 127.9, 125.9, 124.8, 117.6, 51.52, 51.46;
MS m/z (relative intensity) 346 (M+, 100), 283 (25).
Attem p ted BBr 3-Med ia ted Dem eth yla tion of 9. Boron
tribromide (2.8 mL of a 1 M CH2Cl2 solution, 2.8 mmol, 10
equiv) was added to a solution of diester 9 (96 mg, 0.28 mmol)
in 2 mL of CH2Cl2 at -10 °C. The dark red solution was
warmed to rt and, after 24 h at that temperature, poured into
an equal volume of ice-cold 1 M H3PO4. The mixture was
extracted with 2 × 10 mL of CH2Cl2, and the combined organic
phases were washed with brine, dried over Na2SO4, filtered,
and concentrated in vacuo to furnish 79 mg (90%) of 12 as a
1
yellow solid that was clean by H NMR: IR (CCl4) 1697 cm-1
;
1H NMR (360 MHz, CDCl3 + DMSO-d6) δ 8.71 (d, J ) 6.2 Hz,
1H), 8.59 (d, J ) 7.5 Hz, 1H), 8.55 (d, J ) 2 Hz, 1H), 8.47 (d,
J ) 8.5 Hz, 1H), 8.33 (d, J ) 8.2 Hz, 1H), 8.12 (d, J ) 8.4 Hz,
1H), 8.00 (dd, J ) 8.3, 1.8 Hz, 1H), 7.7 (m, 3H), 6.64 (d, J )
16.0 Hz, 1H), 3.83 (s, 3H); 13C NMR (90 MHz, CDCl3 + DMSO-
d6) δ 181.7, 165.7, 136.1, 132.8, 131.9, 131.0, 129.8, 128.6,
127.2, 128.1, 126.5, 125.7, 125.0, 124.1, 123.1, 120.1, 117.2,
50.4; MS m/z (relative intensity) 314 (M+, 35); HRMS calcd
for C21H14O3 314.0943, found 314.0933.
1
cm-1; H NMR (360 MHz, CDCl3) 8.08 (dd, J ) 8.3, 1.3 Hz, 1
H), 7.94 (dd, J ) 8.1, 1.3 Hz, 1 H), 7.88 (d, J ) 16.0 Hz, 1H),
7.87 (dd, J ) 7.0, 1.3 Hz, 1 H), 7.6 (m, 5 H), 7.44 (d, J ) 8.2
Hz, 2 H), 6.60 (d, J ) 16.0 Hz, 1 H), 4.90 (s, 2 H), 4.18 (s, 2 H);
13C NMR (90 MHz, CDCl3) δ 166.7, 165.2, 146.4, 145.4, 138.4,
134.7, 132.8, 131.2, 130.6, 129.6, 129.5, 129.4, 128.83, 128.77,
128.4, 126.6, 124.9, 116.5, 95.2, 94.7, 74.2; MS m/z (relative
2,2,2-Tr ich lor oeth yl 8-Iod o-1-n a p h th ylen eca r boxyla te
(13b). 8-Iodonaphthylenecarboxylic acid (13a )9 (1.53 g, 5.1
mmol) suspended in 5 mL of CH2Cl2 was treated sequentially
with oxalyl chloride (527 µL, 6.2 mmol, 1.2 equiv) and then 1
drop of DMF. A vigorous reaction ensued that resulted in a
homogeneous yellow solution after 5 min at rt. This solution
was concentrated in vacuo, and the residue was redissolved
in 10 mL of CH2Cl2, and (dimethylamino)pyridine (756 mg,
6.2 mmol, 1.2 equiv) followed by 2,2,2-trichloroethanol (596
µL, 6.2 mmol, 1.2 equiv) were added with efficient stirring at
rt. TLC indicated complete consumption of intermediate acid
chloride after 22 h, and so the reaction solution was poured
into an equal volume of ice-cold 1 M H3PO4. The aqueous layer
was extracted with 3 × 20 mL of CH2Cl2, and the combined
organic phases were washed with saturated brine, dried over
Na2SO4, filtered, and concentrated in vacuo to furnish a yellow
oil. Crystallization of the oil from 2:1 hexane/CH2Cl2 afforded
1.06 g of a yellow solid. Flash column chromatography (silica
gel) on the filtrate (10% Et2O/hexane as eluent) furnished an
additional 556 mg of ester 13b as a yellow solid (total ) 1.62
g, 74%). A sample for elemental analysis was prepared by
vapor diffusion crystallization from THF/hexane: mp 85-86
intensity) 580 (M+, 100), 283 (75). Anal. Calcd for C24H16
-
Cl6O4: C, 49.61; H, 2.78; Cl, 36.61. Found: C, 50.01; H, 2.86;
Cl, 36.67.
F r om Sta n n a n e 29a . Ester 13b (4.0 g, 9.3 mmol) and CuI
(89 mg, 0.47 mmol, 0.47 equiv) was dissolved in toluene (100
mL), and a solution of Pd(PPh3)4 (269 mg, 0.23 mmol, 0.025
equiv) in 50 mL of toluene was added followed by the cinnamic
ester 29a (8.0 g, 14 mmol, 1.5 equiv) in toluene (50 mL). After
20 h at reflux, TLC analysis indicated complete consumption
of starting material. The reaction mixture was cooled, filtered
through Celite, and washed with Et2O (3 × 50 mL). The
organic phase was washed with water (100 mL), dried with
Na2SO4, filtered, and concentrated in vacuo to afford a yellow
oil that was purified as above to yield 2.8 g of diester 16 as a
yellow solid (52%).
(E)-8-[4-(Ca r b oxyet h en yl)p h en yl)-1-n a p h t h ylen eca r -
boxylic Acid (17). Diester 16 (415 mg, 0.72 mmol) and
activated Zn (700 mg, 10.7 mmol, 15 equiv) were added to a
solution of 4 mL of HOAc and 40 mL of THF. After vigorous
stirring at rt for 1.5 h, TLC analysis indicated complete
consumption of starting material. The reaction solution was
filtered through Celite, and the zinc-containing residue was
washed with 3 × 20 mL of THF. The filtrate was concentrated
in vacuo to give a white solid that was dissolved in 20 mL of
1 N NaOH. This homogeneous basic solution was washed with
3 × 20 mL of Et2O, treated with activated charcoal, filtered,
and acidified with 1 M H2SO4 until a white precipitate formed.
The aqueous acidic solution was extracted with 3 × 50 mL of
EtOAc, and the combined organic phases were washed with
brine, dried over Na2SO4, filtered, and concentrated in vacuo
to furnish pure diacid 17 as a white solid (180 mg, 79%). Vapor
°C; IR (CCl4) 1745 cm-1 1H NMR (200 MHz, CDCl3) δ 8.24
;
(dd, J ) 7.3, 1.1 Hz, 1 H), 7.91 (td, J ) 7.7, 1.2 Hz, 2 H), 7.81
(dd, J ) 7.2, 1.4 Hz, 1 H), 7.50 (dd, J ) 8.1, 7.2 Hz, 1 H), 7.20
(t, J ) 7.8 Hz, 1 H), 5.11 (s, 2 H); 13C NMR (50 MHz, CDCl3)
δ 167.8, 141.9, 135.4, 132.8, 132.7, 131.3, 129.7, 129.6, 127.6,
125.2, 94.8, 92.5 75.4; MS m/z (relative intensity) 428 (M+, 11),
281 (82). Anal. Calcd for C13H8Cl3IO2: C, 36.34; H, 1.88.
Found: C, 36.48; H, 1.89.
2,2,2-Tr ich lor oeth yl 8-(4-F or m ylp h en yl)-1-n a p h th yl-
en eca r boxyla te (14). Bromide 13b (629 mg, 1.46 mmol), (4-
formylphenyl)boronic acid (10)12 (235 mg, 1.56 mmol, 1.07
equiv), and Pd(PPh3)4 (87 mg, 0.08 mmol, 0.05 equiv) were
added to 5 mL of benzene, 3 mL of 1 M K2CO3, and 2 mL of

Toward Covalently Linked Organic Networks
J . Org. Chem., Vol. 62, No. 25, 1997 8819
diffusion crystallization with THF/hexane afforded a sample
of ice-cold 1 M H3PO4 and extracted with CH2Cl2 (3 × 40 mL).
The organic phase was washed with brine, dried with Na2SO4,
and concentrated in vacuo, and the resulting solid was purified
by flash chromatography on silica gel (20% CH2Cl2/hexane as
eluent) to afford 2.21 g of ester 27a as a white solid (85%):
that decomposed without melting at 322-326 °C: IR (KBr)
1
3457, 1690 cm-1; H NMR (200 MHz, 1:1 CDCl3/DMSO-d6) δ
12.1 (brs, 2 H), 8.04 (dd, J ) 7.9, 1.2 Hz, 1 H), 7.93 (dd, J )
8.0, 1.3 Hz, 1 H), 7.75 (dd, J ) 8.0, 7.0 Hz, 1 H), 7.6-7.4 (m,
8 H), 6.47 (d, J ) 16.0 Hz, 1 H); 13C NMR (50 MHz, 1:1 CDCl3/
DMSO-d6) δ 169.4, 167.0, 143.9, 142.8, 137.7, 133.5, 131.6,
131.1, 130.2, 129.0, 128.0, 127.5, 127.2, 126.7, 126.6, 124.6,
123.7, 117.5; MS m/z (relative intensity) 318 (M+, 100); HRMS
calcd for C20H14O4 318.0892, found 318.0901.
1
mp 174-176 °C; IR (CHCl3) 1738 cm-1; H NMR (200 MHz,
CDCl3) δ 7.77 (d, J ) 7.4 Hz, 1 H), 7.71 (d, J ) 7.2 Hz, 1 H),
7.33 (d, J ) 7.2 Hz, 1 H), 7.20 (d, J ) 7.4 Hz, 1 H), 5.07 (s, 2
H), 3.39 (m, 4 H); 13C NMR (50 MHz, CDCl3) δ 168.2, 150.3,
146.5, 140.8, 134.4, 130.5, 127.2, 125.9, 121.3, 119.2, 114.1,
94.9, 75.1, 30.6, 29.9; MS m/z (relative intensity) 406 (M+,18),
152 (100); HRMS calcd for C15H11O2Cl3Br 406.9008, found
406.9005.
4-Br om o-5-[(2,2,2-tr ich lor oeth oxy)ca r bon yl]-1,8-n a p h -
th a lic An h yd r id e (28a ). K2Cr2O7 (7.4 g, 25 mmol, 7 equiv)
was added to a hot solution of the ester 27a (1.42 g, 3.5 mmol)
in 50 mL of 85% aqueous acetic acid. The mixture was
refluxed for 24 h and cooled, and water (300 mL) was added.
The resulting solution with white precipitate was cooled in ice,
filtered, and washed with copious amounts of water to give
0.90 g of 28a as a white powder (100%): mp 152-153 °C; IR
(CCl4) 1785, 1745 cm-1; 1H NMR (360 MHz, CDCl3) δ 8.74 (d,
J ) 7.5 Hz, 1 H), 8.53 (d, J ) 7.9 Hz, 1 H), 8.24 (d, J ) 7.9 Hz,
1H), 8.02 (d, J ) 7.5 Hz, 1 H), 5.10 (s, 2 H); 13C (50 MHz,
CDCl3) δ 166.3, 159.3, 159.1, 137.3, 134.7, 133.7, 133.1, 131.8,
129.3, 128.7, 127.4, 121.4, 118.6, 94.0, 75.6; MS m/z (relative
intensity) 450 (M+, 3.4), 241 (100); HRMS calcd for C15H7O5-
Cl3Br 450.8542, found 450.8539.
4-(4-For m ylph en yl)-5-[(2,2,2-tr ich lor oeth oxy)car bon yl]-
1,8-n a p h th a lic An h yd r id e (31). Anhydride 28a (1.16 g, 2.6
mmol) and Pd(OAc)2 (60 mg, 0.26 mmol, 0.1 equiv) were
suspended in THF (2.5 mL). To this mixture was added a
solution containing (4-formylphenyl)boronic acid (10) (585 mg,
3.89 mmol, 1.5 equiv), 1 M K2CO3 (7.3 mL, 3 equiv), and 2.5
mL of THF. The mixture was brought to reflux and held there
for 20 h, cooled, filtered through Celite, and washed with water
(2 × 10 mL). The aqueous layer was washed with EtOAc (50
mL), and the organic layers were discarded. The aqueous layer
was acidified with 1 M H2SO4, extracted with EtOAc (6 × 50
mL), dried with Na2SO4, and concentrated in vacuo. The solid
residue was titurated with EtOAc and filtered. The filtrate
was concentrated in vacuo and subjected to flash chromatog-
raphy on silica gel (30% EtOAc/hexane as eluent) to afford the
desired aldehyde 31 as a yellow solid. Additional material was
obtained by refluxing the undissolved solid from the EtOAc
trituration in water (50 mL) and DMSO (5 mL) for 24 h
followed by extracting the aqueous solution with CH2Cl2 (4 ×
100 mL). The organic phase was dried with Na2SO4, filtered,
and concentrated in vacuo to provide a yellow oil that was
dissolved in CHCl3 and concentrated to afford a yellow solid.
Flash chromatography on silica gel (2% EtOAc/CH2Cl2 as
eluent) produced a total of 0.7 g of a yellow solid (64%): mp
198-200 °C; IR (CHCl3) 1786, 1742, 1705 cm-1; 1H NMR (300
MHz, CDCl3) δ 10.12 (s, 1 H), 8.75 (d, J ) 7.6 Hz, 1 H), 8.73
(d, J ) 7.6 Hz, 1 H), 8.11 (d, J ) 7.6 Hz, 1 H), 8.02 (d, J ) 8.2
Hz, 2 H), 7.87 (d, J ) 7.6 Hz, 1 H), 7.61 (d, J ) 8.2 Hz, 2 H),
4.16 (s, 2 H); 13C NMR (75 MHz, CDCl3) δ 191.2, 165.1, 159.6,
159.5, 145.8, 136.2, 133.3, 132.6, 131.5, 130.0, 129.9, 129.5,
126.9, 121.8, 118.7, 93.9, 74.4; MS m/z (relative intensity) 476
(M+,100); HRMS calcd for C22H11O6Cl3 475.9621, found
475.9624.
2,2,2-Tr ich lor oeth yl (E)-4-Ca r boxy-5-[4-[[(2,2,2-Tr ich lo-
r oeth oxy)ca r bon yl]eth en yl]p h en yl)-1,8-n a p h th a lic An -
h yd r id e (30a ). F r om Ald eh yd e 31. 2,2,2-Trichloroethyl
diethoxyphosphonoacetate17a (667 mg, 2.0 mmol, 1.7 equiv) was
dissolved in 5 mL of DMF and added via cannula to a stirring
suspension of degreased NaH (60% suspension in oil, 110 mg,
4.6 mmol, 3.8 equiv) in 5 mL of dry DMF at rt. After gas
evolution had ceased, aldehyde 31 was added in one portion.
After 5 h, TLC indicated complete consumption of 31, and so
the reaction mixture was poured into ice-cold 1 M H3PO4 (5
mL) and extracted with EtOAc (4 × 100 mL). The organic
phase was dried with Na2SO4, filtered, and concentrated in
vacuo. The resulting oil was purified by flash chromatography
on silica gel (30% EtOAc/hexane as eluent) to afford 468 mg
of 30a as a yellow solid (60%): mp 112-114 °C; IR (CHCl3)
Ir r a d ia tion of Cr ysta llin e Dia cid 17. A sample of
recrystallized diacid 17 (48 mg, 0.15 mmol) in a Pyrex flask
was irradiated in a Rayonet photoreactor equipped with 300
nm bulbs (ambient temperature ∼45 °C). TLC monitoring of
small portions quenched with ethereal diazomethane indicated
clean conversion of diacid to a single photoproduct. After 45
h, no starting diacid remained, and so the slightly yellow solid
was suspended in 5 mL of CH2Cl2 and treated with excess
ethereal diazomethane. A few drops of HOAc were added to
quench any remaining diazomethane, the solution was con-
centrated in vacuo, and the residue was purified by flash
chromatography on silica gel (20% Et2O/CH2Cl2) to afford 30
mg of cyclobutane product 20 as a white solid (57%). A sample
obtained by vapor diffusion crystallization with 1,2-dichloro-
ethane/hexane melted at 238-239 °C: IR (CDCl3) 1715 cm-1
;
1H NMR (200 MHz, CDCl3) δ 8.00 (dd, J ) 8.3, 1.3 Ηz, 2 Η),
7.88 (dd, J ) 8.2, 1.2 Ηz, 2 Η), 7.72 (dd, J ) 7.1, 1.4 Ηz, 2 Η),
7.6 (m, 4 Η), 4.53 (dd, J ) 10.6, 7.2 Ηz, 2 Η), 4.08 (dd, J )
10.3, 7.1 Ηz, 2 Η), 3.57 (s, 6 Η), 3.17 (s, 6 Η), 13C ΝΜR (50
ΜΗz, CDCl3) δ 172.4, 170.2, 141.8, 139.1, 137.5, 134.8, 131.9,
131.3, 130.6, 129.0, 128.8, 128.1, 127.4, 125.9, 124.7, 51.9, 51.8,
46.7, 41.5; MS m/z (relative intensity) 692 (M+, 90), 346 (100);
HRMS calcd for C44H36O8 692.2410, found 692.2356.
A sample of crystalline diacid 17 (12.0 mg) taken from the
batch of crystals used for the X-ray structural determination
yielded 12.6 mg of diester 19 (96%) after similar reaction.
Ir r a d ia tion of Dim eth yl Ester 9 in Ben zen e Solu tion .
A sample of recrystallized diester 9 (10 mg, 29 µmol) in 1.5
mL of C6D6 was purged with Ar and irradiated in a Rayonet
photochemical reactor equipped with 300 nm bulbs at rt with
periodic 1H NMR monitoring. After 6 days of exposure, 1H
NMR indicated that all but ∼10% of the starting diester was
consumed. The reaction was concentrated in vacuo, and the
residue was purified by flash column chromatography (silica
gel, 50% Et2O/hexane) to afford 2 mg (20%) of the δ-truxinate
cyclobutane dimer 21 followed by 2 mg (20%) of the â-truxinate
isomer 22. No other cyclobutane-containing products were
detected (1H NMR, TLC).
21: IR (CCl4) 1715 cm-1; 1H NMR (200 MHz, CDCl3) δ 8.00
(dd, J ) 8.2, 1.4 Hz, 2 H), 7.89 (dd, J ) 8.0, 1.6 Hz, 2 H), 7.70
(dd, J ) 7.0, 1.4 Hz, 2 H), 7.5 (m, 6 H), 7.4 (m, 8 H), 3.77 (m,
8 H), 3.58 (m, 2 H), 3.11 (s, 6 H); 13C NMR (50 MHz, CDCl3)
δ 172.8, 170.1, 141.9, 139.4, 134.8, 131.8, 131.3, 130.5, 129.1,
129.0, 128.2, 126.8, 126.0, 124.7, 70.4, 52.2, 51.6, 47.9, 44.5,
MS m/z (relative intensity) 692 (M+, 50), 548 (80), 346 (100);
HRMS calcd for C44H36O8 692.2410, found 692.2391.
22: IR (CCl4) 1712 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.97
(dd, J ) 8.2, 1.2 Hz, 2 H), 7.83 (dd, J ) 8.1, 1.4 Hz, 2 H), 7.68
(dd, J ) 7.1, 1.4 Hz, 2 H), 7.4 (m, 8 H), 7.2 (m, 6 H), 4.50 (d,
J ) 6.4 Hz, 2 H), 3.92 (d, J ) 6.3 Hz, 2 H), 3.78 (s, 6 H), 2.79
(s, 6 H); 13C NMR (50 MHz, CDCl3) δ 173.0, 170.2, 141.4, 139.2,
137.6, 134.9, 132.0, 131.3, 130.7, 129.2, 128.7, 128.2, 127.5,
126.1, 124.8, 63.6, 52.3, 51.5, 45.0, 43.7; MS m/z (relative
intensity) 692 (M+, 45), 346 (100); HRMS calcd for C44H36O8
692.2410, found 692.2441.
2,2,2-Tr ich lor oeth yl 5-Br om o-6-a cen a p h th en eca r box-
yla t e (27a ). 5-Bromo-6-acenaphthenecarboxylic acid (26)15
(1.77 g, 6.4 mmol) was suspended in CH2Cl2 (20 mL). Oxalyl
chloride (664 µL, 7.7 mmol, 1.2 equiv) was added followed by
DMF (2 drops), resulting in immediate gas evolution. The
mixture was stirred at room temperature for 20 min, at which
time the homogeneous solution was concentrated in vacuo and
the residue was redissolved in CH2Cl2 (20 mL). 4-(Dimethyl-
amino)pyridine (939 mg, 7.7 mmol, 1.2 equiv) was added
followed by 2,2,2-trichloroethanol (760 µL, 7.7 mmol, 1.2
equiv). After 8 d, the mixture was poured into an equal volume

8820 J . Org. Chem., Vol. 62, No. 25, 1997
Feldman et al.
1
1784, 1742, 1638 cm-1; H NMR (200 MHz, CDCl3) δ 8.76 (d,
(3 × 200 mL) and then brine, dried over Na2SO4, filtered, and
concentrated in vacuo to afford 2.46 g of 28b as an orange solid
(74%): mp 176-179 °C; IR(CH2Cl2) 1783, 1743 cm-1; 1H NMR
(300 MHz, CDCl3) δ 8.66 (d, J ) 7.5 Hz, 1 H), 8.46 (d, J ) 7.9
Hz, 1 H), 8.18 (d, J ) 7.9 Hz, 1 H), 7.86 (d, J ) 7.5 Hz, 1 H),
4.53 (m, 2 H), 1.15 (m, 2 H), 0.08 (s, 9H); 13C NMR (75 MHz,
CDCl3) δ 168.1, 159.5, 159.3, 139.6, 134.5, 133.4, 133.2, 131.8,
129.1, 128.7, 127.4, 120.6, 118.5, 65.6, 17.1, <1.5; MS m/z
(relative intensity) 422 (M+, 5) 231 (49). Anal. Calcd for
C18H17O5BrSi: C, 51.48; H, 4.08; Br, 18.81. Found: C, 51.56;
H,4.13; Br, 18.86.
J ) 7.6 Hz, 1 H), 8.74 (d, J ) 7.5 Hz, 1 H), 8.10 (d, J ) 7.5 Hz,
1 H), 7.90 (m, 2 H), 7.73 (d, J ) 8.2 Hz, 2 H), 7.51 (d, J ) 8.2
Hz, 2 H), 6.66 (d, J ) 16.0 Hz, 1 H), 4.91 (s, 2 H), 4.20 (s, 2 H);
13C NMR (90 MHz, CDCl3) δ 165.3, 164.8, 146.5, 145.4, 142.4,
136.5, 134.6, 133.3, 132.5, 131.7, 131.4, 129.7, 128.7, 127.2,
121.8, 118.4, 118.0, 95.0, 94.1, 74.5, 74.3; MS m/z (relative
intensity) 648 (M+, 16); HRMS calcd for C26H15O7Cl6 648.8949,
found 648.8954.
F r om Br om id e 28a . Anhydride 28a (1.12 g, 2.5 mmol) was
mixed with CuI (48 mg, 0.25 mmol, 0.1 equiv), and then a
solution of Pd(PPh3)4 (145 mg, 0.125 mmol, 0.05 equiv)
dissolved in 30 mL of toluene, followed by the cinnamic ester
29a in toluene (10 mL), was added. The mixture was heated
to reflux, and after 15 h at reflux, the solution was cooled to
rt, filtered through Celite, and washed with Et2O (2 × 50 mL).
The combined organic phases were washed with water (2 ×
50 mL), dried with Na2SO4, filtered, and concentrated in vacuo,
and the resulting orange oil was purified by flash chromatog-
raphy on silica gel (30% EtOAc/hexane as eluent). Residual
tin compounds were removed by hexane trituration to provide
1.12 g of 30a as yellow solid (69%).
2-(Tr im eth ylsilyl)eth yl (E)-3-[4-(Tr i-n -bu tylsta n n yl)-
p h en yl]p r op -2-en oa te (29b). 2-(Trimethylsilyl)ethyl dieth-
oxyphosphanoacetate17b (2.00 g, 6.75 mmol, 1.1 equiv) was
dissolved in 10 mL of DMF and transferred to a stirring
suspension of degreased NaH (60% suspension in oil, 162 mg,
6.75 mmol, 1.1 equiv) in 10 mL of DMF at 0 °C. After gas
evolution had ceased and the reaction mixture turned clear
yellow (ca. 10 min), 4-(tri-n-butylstannyl)benzaldehyde (2.43
g, 6.14 mmol) in 10 mL of DMF was added. The solution was
allowed to warm to rt and stirred for 2 h, at which time TLC
analysis indicated consumption of the aldehyde. The mixture
was poured into an equal volume of ice-cold 1 M H3PO4 and
extracted with Et2O (3 × 25 mL). The organic phase was
washed with brine (75 mL), dried with Na2SO4, filtered, and
concentrated in vacuo. The resulting yellow oil was purified
by flash chromatography on silica gel (1% Et2O/hexane as
eluent) to afford 2.30 g of 29b as a colorless oil (70%): IR
(CDCl3) 1702 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.66 (d, J )
16.0 Hz, 1H), 7.47 (m, 4H), 6.43 (d, J ) 16.0 Hz, 1H), 4.29 (t,
J ) 8.3 Hz, 2H), 1.32 (m, 6H), 1.29 (m, 8H), 1.10 (m, 6H), 0.88
(t, J ) 7.2 Hz, 9H), 0.067 (s, 9H); 13C NMR (50 MHz, CDCl3)
δ 167.1, 145.9, 144.8, 136.9 (J Sn-C ) 15.1 Hz), 134.0, 127.2
(J Sn-C ) 20.1 Hz), 118.0, 62.6, 29.0 (J C-Sn ) 10.2 Hz), 27.3
2,2,2-Tr ich lor oeth yl (E)-3-[4-(Tr i-n -bu tylsta n n yl)p h en -
yl]pr op-2-en oate (29a). 2,2,2-Trichloroethyl diethoxyphospho-
noacetate (274 mg, 0.84 mmol, 1.2 equiv) was dissolved in 2
mL of DMF and transferred via cannula to a stirring suspen-
sion of degreased NaH (60% suspension in oil, 40 mg, 1 mmol,
1.4 equiv) in 1.5 mL of DMF at rt. After gas evolution had
ceased, 4-(tri-n-butylstannyl)benzaldehyde16 (283 mg, 0.7 mmol)
dissolved in 2 mL of DMF was added. The reaction mixture
was stirred for 6 h, at which time TLC analysis indicated
complete consumption of the aldehyde. The mixture was
poured into an equal volume of ice-cold 1 M H3PO4 and
extracted with Et2O (2 × 50 mL). The organic phase was
washed with brine (50 mL), dried with Na2SO4, filtered, and
concentrated in vacuo. Silica gel flash chromatography (40%
ether/hexane as eluent) afforded 355 mg of 29a as an orange
119
117
(J C-Sn ) 27.7 Hz), 17.4, 13.6, 9.59 (J C-
) 170.6, J C-
)
Sn
Sn
163.0 Hz), -1.50; MS m/z (relative intensity) 537 (M+, 1);
HRMS calcd for C26H46O2SiSn 537.4242, found 537.4756.
2-(Tr im et h ylsilyl)et h yl (E)-4-[[2-(Tr im et h ylsilyl)et h -
oxy]ca r b on yl]-5-[4-[[[2-(t r im et h ylsilyl)et h oxy]ca r b on -
yl]eth en yl]p h en yl]-1,8-n a p h th a lic An h yd r id e (30b). An-
hydride 28b (0.97 g, 2.3 mmol), copper(I) iodide (61 mg, 0.32
mmol, 0.14 equiv), and stannylcinnamic ester 29b (1.48 g, 2.8
mmol, 1.2 equiv) were combined in 15 mL of toluene. Pd-
(PPh3)4 (185 mg, 0.16 mmol, 0.07 equiv) in 15 mL of toluene
was added to the reaction mixture, and the red solution was
heated to reflux and held there for 22 h. At that time, the
solution was cooled to rt and filtered through Celite. The
filtrate was washed with water (2 × 40 mL) and brine, dried
over Na2SO4, filtered, and concentrated in vacuo. The red-
brown solid was triturated with 50 mL of hexane. The solid
residue was dried in vacuo to afford 1.06 g of the diester 30b
as a red-brown solid (78%). Vapor diffusion crystallization
from CH2Cl2/hexane resulted in a sample melting at 188-190
oil (89%): IR (CHCl3) 1723, 1634 cm-1; H NMR (300 MHz,
1
CDCl3) δ 7.81 (d, J ) 16.0 Hz, 1 H), 7.51 (m, 4 H), 6.54 (d, J
) 16.0 Hz, 1 H) 4.87 (s, 2 H), 1.53 (m, 6 H), 1.35 (m, 6 H), 1.07
(m, 6 H), 0.88 (t, J ) 7.2 Hz, 9 H); 13C (90 MHz, CDCl3) δ
165.2, 147.5, 147.1, 137.0, 133.5, 127.4 (J C-Sn ) 19.9 Hz), 115.8,
119
95.2, 74.1, 29.8, 27.3 (J C-Sn ) 27.8 Hz), 13.6, 9.7 (J C-
)
Sn
117
170.8 Hz, J C-
) 163.2 Hz); MS m/z (relative intensity) 511
Sn
(M+ - Bu, 100); HRMS calcd for C19H26O2Cl3Sn (M+ - Bu)
511.0042, found 511.0020.
2-(Tr im eth ylsilyl)eth yl 5-Br om o-6-a cen a p h th en eca r -
boxyla te (27b). 5-Bromo-6-acenaphthenecarboxylic acid (26)
(1.90 g, 6.8 mmol) was suspended in 25 mL of thionyl chloride
(343 mmol, 50 equiv) at rt. After 3 h of vigorous stirring, the
now homogeneous orange solution was concentrated in vacuo.
4(-Dimethylamino)pyridine (1.16 g, 9.5 mmol, 1.4 equiv) was
added followed by 9 mL of CH2Cl2 and 2-(trimethylsilyl)ethanol
(1.1 mL, 7.5 mmol, 1.1 equiv). After 60 h at rt, the dark brown
solution was poured into 15 mL of 1 M H3PO4. The aqueous
layer was extracted with CH2Cl2 (3 × 20 mL), and the
combined organic phases were washed with brine, dried over
Na2SO4, filtered, and concentrated in vacuo to furnish 2.09 g
of a brown residue. Flash column chromatography of this
material on silica gel (5% EtOAc/hexane as eluent) afforded
1.81 g of ester 27b as a light yellow solid (63%): mp 96-98
°C (recryst EtOAc); IR (CH2Cl2) 1719 cm-1; 1H NMR (300 MHz,
CDCl3) δ 7.54 (d, J ) 7.4 Hz, 1 H), 7.45 (d, J ) 7.1 Hz, 1 H),
7.08 (d, J ) 7.1 Hz, 1 H), 6.93 (d, J ) 7.4 Hz, 1 H), 4.43 (m, 2
H), 3.12 (m, 4H), 1.09 (m, 2 H), 0.00 (s, 9 H); 13C NMR (75
MHz, CDCl3) δ 170.2, 148.9, 146.1, 140.4, 133.8, 129.5, 127.8,
126.8, 120.7, 118.9, 114.0, 63.8, 30.2, 29.5, 17.0, -1.6; MS m/z
(relative intensity) 378 (M+, 7), 269 (52).
1
°C: IR (CH2Cl2) 1781, 1741, 1716 cm-1; H NMR (360 MHz,
CDCl3) δ 8.71 (d, J ) 7.6 Hz, 1 H), 8.69 (d, J ) 7.5 Hz, 1 H),
7.96 (d, J ) 7.5 Hz, 1 H), 7.82 (d, J ) 7.6 Hz, 1 H), 7.71 (d, J
) 16.1 Hz, 1 H), 7.65 (d, J ) 8.2 Hz, 2 H), 7.45 (d, J ) 8.2 Hz,
2 H), 6.50 (d, J ) 16.0 Hz, 1 H), 4.33 (m, 2 H), 3.55 (m, 2 H),
1.08 (m, 2 H), 0.81 (m, 2 H), 0.08 (s, 9 H), -0.04 (s, 9 H); 13C
NMR (90 MHz, CDCl3) δ 167.6, 166.7, 159.9, 147.0, 142.9,
142.0, 139.0, 134.8, 133.1, 132.7, 131.6, 131.2, 129.4, 129.2,
128.2, 127.1, 120.8, 119.8, 118.0, 64.7, 62.9, 17.3, 17.0, -1.5,
-1.6; ΜS m/z (relative intensity) 589 (M+, 0.9) 518 (10).
Ack n ow led gm en t. This work was supported by the
NSF under the auspices of CHE9321787.
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR spectra for compounds 9, 11, 12, 17, 20-22, 27a ,b, 28a ,
29a ,b, 30a ,b, and 31 and copies of diagnostic regions of the
1H NMR spectra of the methyl esters of R-truxillic, ꢀ-truxillic,
â-truxinic, and δ-truxinic acids (26 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
4-Br om o-5-[[2-(t r im et h ylsilyl)et h oxy]ca r b on yl]-1,8-
n a p h th a lic An h yd r id e (28b). Ester 27b (2.99 g, 7.9 mmol)
in 89 mL of 85% aqueous HOAc was treated with K2Cr2O7 (12.2
g, 41.3 mmol, 5.2 equiv), and the mixture was heated to 95 °C
for 5 h. The orange solution was cooled to rt and then poured
into 200 mL of ice-water. The resulting white solution/
suspension was extracted with EtOAc (3 × 200 mL). The
combined organic phases were washed with saturated NaHCO3
J O9714167