A test for homology: Photoactive crystalline assemblies involving linear templates based on a homologous series of phloroglucinols

Article abstract of DOI:10.1021/ol0484052

(Chemical Equation Presented) Cocrystallization of trans-1,2-bis(4-pyridyl) ethylene (4,4′-bpe) with eight members of a homologous series of phloroglucinols 1a-h yields molecular solids 2(1a-h)·2(4,4′-bpe) with components held together by four O-H...N hydrogen bonds. In each case, the molecules assemble to form a discrete four-component assembly with olefins preorganized for a [2 + 2] photodimerization. UV irradiation of each member in the series of solids produces rctt-tetrakis(4-pyridyl)cyclobutane (4,4′-tpcb), stereospecifically, in up to 100% yield.

Full text of DOI:10.1021/ol0484052

ORGANIC
LETTERS
2
004
Vol. 6, No. 25
647-4650
A Test for Homology: Photoactive
Crystalline Assemblies Involving Linear
Templates Based on a Homologous
Series of Phloroglucinols
4
Tomislav Fri sˇ cˇ i c´ , David M. Drab, and Leonard R. MacGillivray*
Department of Chemistry, UniVersity of Iowa, Iowa City, Iowa 52242-1294
len-macgilliVray@uiowa.edu
Received August 11, 2004 (Revised Manuscript Received October 27, 2004)
ABSTRACT
Cocrystallization of trans-1,2-bis(4-pyridyl)ethylene (4,4
solids 2(1a h) 2(4,4 -bpe) with components held together by four O
discrete four-component assembly with olefins preorganized for a [2
solids produces rctt-tetrakis(4-pyridyl)cyclobutane (4,4 -tpcb), stereospecifically, in up to 100% yield.
′
-bpe) with eight members of a homologous series of phloroglucinols 1a
‚‚‚N hydrogen bonds. In each case, the molecules assemble to form a
2] photodimerization. UV irradiation of each member in the series of
−h yields molecular
−
‚
′
−H
+
′
A fundamental basis for the success of synthetic organic
chemistry is an ability to make covalent bonds using
homologous series of compounds. Homology enables chem-
subtle structural changes to molecules5,6 has meant that
methods to organize molecules in the solid state to react have
been largely based on “hit-or-miss” strategies which, de facto,
have prohibited an ability to conduct molecular solid-state
1
ists to make systematic changes to the structures of reactants
3
(e.g., -methyl, -ethyl, and -propyl) while maintaining identical
synthesis by design. A general means to conduct molecular
chemical reactivities. The ability to make systematic changes
to reactants has, in turn, equipped chemists with a means
to conduct molecular synthesis by design (e.g., natural
products).2
synthesis in the solid state could provide deliberate, solvent-
free access to molecules and materials (e.g., switches), that
may be difficult, or impossible, to achieve in the liquid phase.
We have introduced a method, based on principles of
supramolecular chemistry, to direct the formation of covalent
bonds in solids using molecules that function as linear
Whereas homology has developed such that the concept
is now “assumed” applicable in the liquid phase, the idea,
3,4
7,8
although explored, has been markedly less successful in
the solid state. Indeed, the sensitivity of crystal packing to
templates. The templates (e.g., resorcinol) assemble reac-
tants (e.g., trans-1,2-bis(4-pyridyl)ethylene or 4,4′-bpe) via
(
1) Corey, E. J. Pure Appl. Chem. 1967, 14, 19.
(5) Desiraju, G. R. Angew. Chem., Int. Ed. Engl. 1995, 34, 2311.
(6) 6-Acetoxycoumarin, for example, is photoactive while 4-methyl-6-
acetoxycoumarin is photostable (see: Gnanaguru, K.; Ramasubbu, N.;
Venkatesan, K.; Ramamurthy, V. J. Org. Chem. 1985, 50, 2337).
(7) MacGillivray, L. R.; Reid, J. L.; Ripmeester, J. A. J. Am. Chem.
Soc. 2000, 122, 7817.
(2) Nicolau, K. C.; Vourloumis, D.; Winssinger, N.; Baran, P. S. Angew.
Chem., Int. Ed. 2000, 39, 44.
(
3) Schmidt, G. M. J. Pure Appl. Chem. 1971, 27, 647.
(4) (a) Ito, Y.; Borecka, B.; Trotter, J.; Scheffer, J. R. Tetrahedron Lett.
1
995, 36, 6083. (b) Leibovitch, M.; Olovsson, G.; Scheffer, J. R.; Trotter,
J. J. Am. Chem. Soc. 1998, 120, 12755. (c) Tanaka, K.; Mochizuki, E.;
Yasui, N.; Kai, Y.; Miyahara, I.; Hirotsu, K.; Toda, F. Tetrahedron 2000,
(8) Similar methods: (a) Shan, N.; Jones, W. Tetrahedron Lett. 2003,
44, 3687. (b) Amirsakis, D. G.; Garcia-Garibay, M. A.; Rowan, S. J.;
Stoddart, J. F.; White, A. J. P.; Williams, D. J. Angew. Chem., Int. Ed.
2001, 40, 4256.
5
6, 6853. (d) Sharma, C. V. K.; Panneerselvam, K.; Shimoni, L.; Katz, H.;
Carrell, H. L.; Desiraju, G. R. Chem. Mater. 1994, 6, 1282.
1
0.1021/ol0484052 CCC: $27.50
© 2004 American Chemical Society
Published on Web 11/12/2004

Figure 1. Schematic of the targeted assemblies.
hydrogen bonds within discrete molecular assemblies, such
as 2(resorcinol)‚2(4,4′-bpe), for single and multiple [2 + 2]
photodimerizations. The flexibility of the approach, owing
to the ability of the templates to assemble along the exteriors
of the reactants and, in doing so, isolate reactants from
vexatious effects of crystal packing, has enabled us to
7
construct a [2.2]paracyclophane and, very recently, [n]-
9
ladderanes (where n ) 3 and 5) in solids.
To place our method on firmer grounds, we believe it will
be necessary to determine the tolerance of the assembly
process to systematic changes to the constituent components.
The modular nature of the approach means that the concept
of homology can be applied to both the templates and
reactants. Here, we describe our first test to determine the
tolerance of the assembly process to a homologous series of
components. Our focus is the template. Specifically, we have
attached a series of -R groups (e.g., -alkyl) to a phloroglucinol
Figure 2. ORTEP perspectives of (a) 2(1a)‚2(4,4′-bpe), (b) 2(1g)‚
2(4,4′-bpe), and (c) 2(1h)‚2(4,4′-bpe). Color scheme: red ) oxygen,
blue ) nitrogen, gray ) carbon, white ) hydrogen.
phloroglucinol with a homologous series of nitriles was
anticipated to give 1b-h. A search of the Cambridge
Structural Database suggested that a hydroxyl group of 1a-h
could form an intramolecular O-H‚‚‚O hydrogen bond with
(Figure 1) and demonstrate that the assembly process involv-
12
ing 4,4′-bpe is tolerant to the -R groups in 2(1a-h)‚2(4,4′-
bpe) and that photoreactivity, despite changes to packing of
the crystalline assemblies, is maintained in all cases.
Our desire to modify the template stems from our
demonstration of “template-switching”.10 We revealed that
switching the template (e.g., resorcinol) to a derivative (e.g.,
the carbonyl moiety and thereby render 1a-h a bifunctional
template. Thus, cocrystallization of 1a-h with 4,4′-bpe
would give 2(1a-h)‚2(4,4′-bpe) with olefins positioned
linearly for a [2 + 2] photodimerization to form, stereo-
specifically, rctt-tetrakis(4-pyridyl)cyclobutane (4,4′-tpcb).
Compounds 1b-h were synthesized via Houben-Hoesch
reaction with the appropriate nitrile. Single crystals of 2(1a-
c)‚2(4,4′-bpe) and 2(1e-h)‚2(4,4′-bpe) were grown by
allowing a saturated solution of 4,4′-bpe and 1a-h (ratio
1:1) in MeCN to stand during 1 day. Single crystals of 2(1d)‚
2(4,4′-bpe) were grown by allowing a saturated solution of
the components in ethyl acetate to evaporate at 50 °C over
1 day. The formulations of 2(1a-h)‚2(4,4′-bpe) were
4
-benzylresorcinol) can alter crystal packing so as to affect
10b
10a
molecular orientation and product yield. Consequently,
there is a need to modify the template to control structural
and bulk physical properties of such reactive solids. More-
over, an ability to modify the template systematically could
permit the properties of such reactive solids to be fine-tuned.
To develop a template amenable to systematic modifica-
tion, we turned to commercially available phloroglucinal-
13
1
confirmed via single-crystal X-ray diffraction and H NMR
1
1
dehyde 1a and its congeners. Houben-Hoesch reaction of
spectroscopy.
(
9) Gao, X.; Fri sˇ cˇ i c´ , T.; MacGillivray, L. R. Angew. Chem., Int. Ed. 2004,
3, 232.
10) (a) Fri sˇ cˇ i c´ , T.; MacGillivray, L. R. Chem. Commun. 2003, 1306.
b) MacGillivray, L. R.; Reid, J. L.; Ripmeester, J. A.; Papaefstathiou, G.
S. Ind. Eng. Chem. Res. 2002, 41, 4494.
(11) (a) Hoesch, K. Ber. 1915, 48, 1122. (b) Houben, J. Ber. 1926, 59,
2878.
(12) Begley, M. J.; Crombie, L.; King, R. W.; Slack, D. A.; Whiting, D.
A. J. Chem. Soc., Perkin Trans. 1 1977, 21, 2393. CCDC reference codes:
FORCIT10 and ACCITR10.
4
(
(
4648
Org. Lett., Vol. 6, No. 25, 2004

Table 1. Structure Data and Yields for 2(1a-h)·2(4,4′-bpe)
O(1,2)‚‚‚N(1,2)
distances (Å)
d1a
(Å)
d2b
(Å)
yield
(%)
template
R
1
1
1
1
1
1
1
1
a
b
c
d
e
f
H
CH3
2.693(3) 2.733(3) 3.79 7.44
2.720(3) 2.718(3) 3.69 4.79
2.724(3) 2.718(3) 3.87 4.95
2.743(3) 2.694(3) 3.88 5.16
2.714(2) 2.745(2) 3.92 4.71
2.714(3) 2.733(3) 3.76 4.95
2.741(6) 2.707(6) 3.91 4.23
2.752(2) 2.693(2) 3.95 5.85
96
65
65
92
87
100
81
50
C2H5
C3H8
C4H9
C5H11
C6H13
C6H5
g
h
a
d1 represents the distance between carbon atoms of double bonds within
b
a hydrogen-bonded assembly. d2 represents the distance between carbon
atoms of double bonds between adjacent assemblies.
Structure studies reveal (Figure 2) that the components of
each solid assemble to form discrete four-component mo-
lecular assemblies 2(1a-h)‚2(4,4′-bpe), held together by four
O-H‚‚‚N hydrogen bonds. As anticipated, a single hydroxyl
group of 1a-h participates in an intramolecular O-H‚‚‚O
Figure 3. 1H NMR spectra of 2(1a)‚2(4,4′-bpe) (a) before and (b)
after photoreaction (yield 96%).
hydrogen bond with each carbonyl moiety, which enables
each triol to serve as a ditopic receptor14 and participate in
nearest-neighbor assemblies while in 2(1b-c)‚2(4,4′-bpe) the
C-H‚‚‚π interactions are effectively replaced by C-H‚‚‚O
the O-H‚‚‚N forces (Table 1). Each -R group is projected
away from the center of 1a-h and the olefins of each
assembly lie parallel and separated by <4.2 Å, geometries
1
6
forces between the terminal methyl groups and hydroxyl
groups involved in the intramolecular hydrogen bond. Further
lengthening of the aliphatic chain in 2(1d-g)‚2(4,4′-bpe)
that conform to the topochemical postulates of Schmidt for
1
7
3
results in interdigitation of the chains while the phenyl
[
2 + 2] photoreaction. Moreover, these observations dem-
group of 1h enables weak O-H‚‚‚O hydrogen bonds
onstrate that the assembly process involving 1a-h and 4,4′-
bpe is tolerant to the series of -R groups which, in turn,
enables each triol to position each olefin for reaction.
The tolerance of the assembly process to each -R group
translates into reactivity in each solid. Ultraviolet (UV)
irradiation (broadband Hg lamp) of powdered crystalline
samples of 2(1a-h)‚2(4,4′-bpe) reveals that each olefin reacts
i
between neighboring assemblies [d(O4‚‚‚O3 ) ) 3.262 Å,
symmetry operator i ) -x + 3, -y - 1, -z - 1]. Despite
these structural differences, however, the separation between
carbon atoms of double bonds of nearest-neighbor assemblies
in each solid is larger than the corresponding distance within
the assembly (Table 1). Thus, in addition to supporting the
1
to give, stereospecifically, 4,4′-tpcb, as confirmed by H
NMR spectroscopy (Figure 3). The identity of 4,4′-tpcb is
confirmed by the emergence of cyclobutane protons at 4.66
ppm (singlet, DMSO-d
6
). Similar to 2(R-resorcinol)‚2(1,4-
bpeb) (where R ) 5-methoxy, 4-benzyl),1 the yields of the
0
1
5
photoreactions are different, ranging from 50% to 100%.
That each photoreaction of 2(1a-h)‚2(4,4′-bpe) occurs
within each hydrogen-bonded assembly is further realized
by the packing of the assemblies in each solid (Figure 4).
Specifically, the assemblies form sheets held together,
depending on the -R group, by four different bonding motifs.
In 2(1a)‚2(4,4′-bpe), adjacent assemblies participate in C-
H‚‚‚π forces involving aldehyde and pyridine units of
(
13) See the Supporting Information for 2(1a-h)‚2(4, 4′-bpe) crystal
data.
(
14) (a) Kelly, T. R.; Zhao, C.; Bridger, G. J. J. Am. Chem. Soc. 1989,
1
11, 3744. (b) Rebek, J., Jr. Angew. Chem., Int. Ed. Engl. 1990, 29, 245.
(
c) Bassani, D. M.; Darcos, V.; Mahony, S.; Desvergne, J.-P. J. Am. Chem.
Soc. 2000, 122, 8795.
(
15) A correlation of yield with the orientation of reactive carbon-carbon
double bonds was not observed (see the Supporting Information), which
suggests that mechanical properties of each solid may play a role in
determining the yield; see: (a) McBride, J. M. Acc. Chem. Res. 1983, 16,
Figure 4. Mixed wireframe (template) and space-filling (olefin)
perspectives of the packing of (a) 2(1a)‚2(4,4′-bpe), (b) 2(1g)‚2(4,4′-
bpe), and (c) 2(1h)‚2(4,4′-bpe).
3
04. (b) Ramamurthy, V.; Venkatesan, K. Chem. ReV. 1987, 87, 433.
(
16) Desiraju, G. R. Acc. Chem. Res. 1996, 29, 441.
Org. Lett., Vol. 6, No. 25, 2004
4649

formation of each discrete structure, each -R group serves
a secondary role of prohibiting cross-reactions between
adjacent assemblies by giving rise to different crystal packing
arrangements in each solid.18
targeting functional groups of increasing complexity to
engineer templates with applications in chemical synthesis
(e.g., chiral groups) and materials science (e.g., chro-
mophores).
In this report, we have established that an assembly process
involving a series of components is tolerant to systematic
changing of -R groups. Specifically, all members of a
homologous series of phloroglucinols have been shown to
function as linear templates by assembling 4,4′-bpe via
hydrogen bonds within discrete molecular assemblies in the
solid state for [2 + 2] photoreaction. With an ability to
systematically modify the template achieved, we are now
Acknowledgment. We thank the National Science Foun-
dation (CAREER Award, L.R.M., DMR-0133138) for sup-
port of this work.
Supporting Information Available: Crystallographic
reports and tables of positional and thermal parameters, bond
lengths and angles, parameters describing the positioning of
double bonds, and NMR data. This material is available free
of charge via the Internet at http://pubs.acs.org.
(
17) Menger, F. M.; Lee, J.-J.; Hagen, K. S. J. Am. Chem. Soc. 1991,
13, 4017.
18) Photoreactivities in solids based on cinnamic acid have been
classified according to R-, â-, and γ-packing motifs (see ref 3).
1
(
OL0484052
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Org. Lett., Vol. 6, No. 25, 2004