Valine sulfonamidecinnamic acid asymmetric crystal reactions

Article abstract of DOI:10.1039/c1cc15068e

Racemic and homochiral valine sulfonamidecinnamic acids crystallize with components aligned by use of the complementary features of hydrogen bonds and molecular topology to give supramolecular dimers. These discrete motifs effectively organize adjacent ol

Full text of DOI:10.1039/c1cc15068e

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COMMUNICATION
Valine sulfonamidecinnamic acid asymmetric crystal reactionsw
Kraig A. Wheeler,* Steven H. Malehorn and Annie E. Egan
Received 15th August 2011, Accepted 8th November 2011
DOI: 10.1039/c1cc15068e
Racemic and homochiral valine sulfonamidecinnamic acids crystallize
with components aligned by use of the complementary features of
hydrogen bonds and molecular topology to give supramolecular
dimers. These discrete motifs effectively organize adjacent ole-
fins for UV initiated single-crystal-to-single-crystal [2+2]
photodimerization reactions. The racemic crystals produce
inversion related cyclobutane products, while the desymmetrized
crystalline architectures of the homochiral phase promote
asymmetric photodimerization with 90% conversion.
assists the alignment of neighboring reactive moieties. Progress
realized in this field continues to offer much needed insight to the
design and operational aspects of generating robust supramolecular
synthons that exhibit solid-state reactivity. One remaining
high-impact goal centers on successfully merging the structural
predictability of these approaches with asymmetric reaction
outcomes. Imprinting chirality on reaction processes provides
a significant challenge that, if successful, promises consider-
able return to the scientific community in the form of new
materials and applications. Essential outcomes now go beyond
mild chemo- and stereoselective control and rest firmly
with developing robust methods that result in high-yielding
asymmetric syntheses. A recent review of this area illustrated
several important examples that make use of unimolecular
systems and enantiomorphic crystallization to control and
preserve homochirality.6 The principles of ‘‘crystal engineering’’
also emerged in this context; however, amplifying the predictability
of these structural results to ‘‘total’’ asymmetric transformations
remains a formidable challenge.6,7
Enhanced specificity and efficiency are hallmarks of chemical
transformations that control molecular motion. Restricting
the movement of components holds much importance to the
development of functional materials such as catalysts1 and
molecular devices,2 where the desired property frequently
stems from a localized structural bias due to the combined
effects of molecular shape and non-bonded contacts. While
limiting motion can provide opportunities to differentiate reaction
pathways or recognition profiles, high performance materials that
result in complete or near quantitative selectivity require exquisite
control of individual process components.
Our recent attention to solid-state reactions developed an
effective method for organizing chiral reactive components in
the absence of secondary molecular/metal center templates.8 As
shown in Scheme 1, this strategy exploits sulfonamidecinnamic
acid frameworks that form robust supramolecular dimers due to
the features of molecular topology and directionality of hydrogen
bonds. These dimeric motifs persist regardless of the use of
racemic (rac)-1, quasiracemic [(R)-1/(S)-2], and homochiral single
component (R)-1 building-blocks. Each of these systems under-
goes topochemically controlled9 single-crystal-to-single-crystal
(SCSC) photodimerization reactions in high yield (61–100%
conversion). In the case of quasiracemate (R)-1/(S)-2 and single
component (R)-1, the homochiral molecules exert asymmetric
induction on crystal growth and supramolecular dimer formation
that ultimately translates to homochiral photodimer products.
The current study presents several interesting opportunities to
Though conceptually similar to the localized effects of solution
processes, molecules aligned in crystalline architectures offer
considerable advantage for enhanced spatial control. This benefit
arises from building-blocks with fixed positions exhibiting
long-range order. The intrinsic benefits of lattice-controlled
molecules have long been realized with practical opportunities
to produce new generation functional materials.3 Utilizing
crystalline architectures as de novo reaction vessels is one
notable area that has attracted significant attention.
The unparalleled success of solid-state reactions over the
last decade can partially be attributed to the identification and
development of well-defined structural motifs.4 Because motif
prediction has evolved from exploration-based studies to more
focused approaches utilizing a bottom-up design,5 it is not
surprising that reports of programmed reactivity from codified
structural architectures are more commonplace in the literature.
This collective work is largely directed at heteromeric assemblies,
where at least one molecular component5d–e or metal center5f–g
Department of Chemistry, Eastern Illinois University, Charleston
Illinois, USA. E-mail: kawheeler@eiu.edu; Tel: 01 217 581 3119
w Electronic supplementary information (ESI) available: Synthetic
procedures, photochemical details, and full crystal structure tables for
(rac)- and (R)-3. CCDC 838809–838812. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c1cc15068e
Scheme 1 Photoactive sulfonamidecinnamic acid frameworks (left)
and supramolecular alignment of hydrogen-bonded dimers (right).
c
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Chem. Commun., 2012, 48, 519–521 519

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explore the supramolecular and photoreactive boundaries of
this sulfonamidecinnamic acid framework. Use of racemic and
homochiral valine 3 introduces an isopropyl group, spatially
larger than Me and Et, into the structural framework that
allows examination of the transferability of this approach and
the role of the R group to crystal packing and solid-state
photodimerization.
A single crystal of (rac)-3 was illuminated using a
200W Xe(Hg) lamp and the long wavelength tail-irradiation
technique.11w Because no appreciable crystal degradation was
observed, reaction progress was periodically monitored by
collecting full sets of X-ray data.z Refinement of the
occupancy factors for the reactant and product phases provided
a straightforward method for analysing this SCSC transformation.
This photodimerization process proceeded in 68% conversion
after 7.2 h of exposure (Fig. 2).
The target racemic and homochiral compounds of 3 were
prepared using a straightforward two-step process.w Crystals
of each phase were grown by slow evaporation of acetone
solutions and assessed by X-ray crystallography.z In the case
of (rac)-3, inspection of the crystal structure revealed components
with the anticipated fishhook conformations organized into
inversion related supramolecular dimers, topologically similar
to those reported by Feldman et al.10 (Fig. 1a). Each motif is
stabilized by the complementary features of molecular shape
and carboxylꢀꢀꢀcarboxyl hydrogen bonds that effectively aligns
adjacent olefins with o3.8 A separation. The discrete pattern
present in (rac)-3 is nearly indistinguishable to those reported for
the alanine and butyrate phases8a [i.e. (rac)-1, (R)-1/(S)-2] and,
thus highlights the strong preference of sulfonamidecinnamic
acids to form supramolecular dimers.
Though our original program design of sulfonamidecinnamic
acids focused on exploiting the inversion symmetry (or near
inversion symmetry) preferences12 of organic racemates and
quasiracemates, early success with these materials prompted
further study of more diverse chemical systems. At first we
reasoned that chiral single-component compounds, e.g. (R)-1,
seemed unlikely candidates given such materials, when
recrystallized, form desymmetrized motifs lacking the desired
inversion symmetry requirement. To our surprise, slow
evaporation crystal growth of (R)-1 from acetone and 2-butanone
resulted in three polymorphic forms; each displaying approximate
centrosymmetric supramolecular dimers.8b In addition to (rac)-3,
this paper also examines the structure of homochiral valine (R)-3
that further strengthens the importance of the central sulfo-
namidecinnamic acid framework to hydrogen-bond dimer
construction. (R)-3 crystallized in space group P1 with two
symmetry independent molecules (Z0 = 2). Fig. 3 shows these
molecular pairs assemble into homomeric dimers with short
3.81 A olefinic spacing. While rigorously chiral, these motifs
exhibit a remarkable degree of centrosymmetry as indicated by
a low S(Ci) value (0.14) determined using Avnir’s Continuous
Symmetry Method.13 The alignment of dimers in the crystal
follows a similar pattern observed for racemate 3, where the
increased spatial properties of the isopropyl group in (R)-3
divert the structure from close-packed infinite stacks of olefins
to isolated dimers.
The pendant isopropyl group of racemic 3 provides a critical
departure from the crystal packing motifs generated by
compounds 1 and 2. As shown in Fig. 1 (right), assessment
of these previous structures revealed hydrogen-bonded dimers
with favorable olefinꢀ ꢀ ꢀolefin alignment for both the intra- and
interdimer motifs. Though the X-ray data suggested [2+2]
cycloaddition preferentially occurred by the intradimer path,
products generated via an interdimer process could not
be initially discounted. In view of this potential structural
dilemma, how to effectively isolate these hydrogen-bonded
dimers in the solid-state raises an important challenge. Compound
(rac)-3 effectively circumvents this issue by use of the spatial
properties of the pendant isopropyl group; where the steric bulk
of this group disrupts the close alignment of interdimer olefins and
displaces adjacent dimers with a slip distance of B3.0 A. Because
the CQC groups of these next nearest neighbors are separated
by 4.5 A, the increased size of R supplies an effective structural
handle to isolate the hydrogen bonded motifs and, in turn, the
photodimerization process.
Photodimerization of a single crystal of (R)-3 via tail-
irradiation resulted in asymmetric synthesis of the cyclobutane
product. Reaction progress was again scrutinized by X-ray
crystallography (Fig. 4, top). At 15% conversion (20 min),
crystal quality greatly diminished as evident from visual
inspection of the sample (crystal fractures and discoloration)
and diffuse, less-intense reflections in the X-ray diffraction
pattern. A powder sample of (R)-3 was then treated with
1
unfiltered UV radiation and periodically assessed by H NMR.
As shown in Fig. 4 (bottom), the distinct NMR signals of
the olefin (6.7 and 7.7 ppm) and cyclobutane (4.1 and
4.5 ppm) protons allow evaluation of the reaction progress.
Fig. 1 Two views of the crystal structure of (rac)-3 showing the
(a) asymmetric unit (50% probability) and packing motif and
(b) formation of extended hydrogen-bond motifs.
Fig. 2 Crystal structure of UV-irradiated (rac)-3 indicating reactant
and cyclobutane product phases (32 : 68, 7.2 h).
c
520 Chem. Commun., 2012, 48, 519–521
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(4857 unique, two-component twin), R1 = 0.0423 and wR2
0.1077 [I 4 2s(I)], Rint = 0.0461, GOF = 1.08, flack = 0.54(6).
Crystal data for (R)-3 (photodimerized): C28H34N2O12S2, Mr
=
=
654.71, Triclinic space group P1, a = 7.8647(3), b = 8.0522(3), c =
11.7930(5) A, a = 83.951(2), b = 77.725(2), g = 89.754(2)1,
V = 725.57(5) A3, Z = 1, Dc = 1.498 g cmꢁ3, m = 2.270 mmꢁ1
,
F000 = 344, T = 100(2)K, 2ymax = 67.321, 4698 reflections collected
(4698 unique, two-component twin), R1 = 0.0499 and wR2 = 0.1250
[I 4 2s(I)], Rint = 0.0581, GOF = 1.03, flack = 0.09(2).
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probability) and spatial influence of the isopropyl group.
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Fig. 4 Solid-state photodimerization of (R)-3 assessed using
1
single-crystal X-ray diffraction (top) and H NMR (bottom).
Such experimental results indicate a time dependent decrease
in reactant and increase in product signals with 90% conver-
sion (67 h).
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In summary, the persistent formation of supramolecular
dimers underscores this approach as a viable method for
organizing programmed reactivity in molecular crystals.
Despite the chemical and spatial diversity of alkyl groups
inspected to date (i.e. Me, Et, and i-Pr), the recognition
profiles of these sulfonamidecinnamic acids result in fish hook
conformations and discrete motifs that efficiently direct [2+2]
photocylcoaddition reactions. Both (rac)-3 and (R)-3 undergo
remarkable SCSC transformations that result in achiral and
homochiral photoproducts, respectively.
This work was supported by the National Science Founda-
tion (CHE-0957391 and CHE-0722547).
Notes and references
z Crystallographic data. X-ray diffraction data for (rac)- and (R)-3
were collected with a Bruker APEX-II equipped with a graphite-
monochromator using Cu-Ka radiation (l = 1.54178 A).
Crystal data for (rac)-3 (reactant): C14H17NO6S, Mr = 327.35,
%
Triclinic space group P1, a = 7.2401(1), 7.2996(1), c = 15.8742(3) A,
a = 88.734(1), b = 87.853(1), g = 64.951(1)1, V = 759.49(2) A3, Z = 2,
Dc = 1.431 g cmꢁ3, m = 2.169 mmꢁ1, F000 = 344, T = 100(2)K,
2ymax = 68.241, 15 072 reflections collected (2710 unique), R1 = 0.0485
and wR2 = 0.1270 [I 4 2s(I)], Rint = 0.0467, GOF = 1.12.
Crystal data for (rac)-3 (photodimerized): C28H34N2O12S2, Mr = 654.71,
Triclinic space group P1, a = 7.4391(3), b = 7.6719(3), c = 15.0529(7) A,
a = 88.371(3), b = 85.421(3), g = 61.552(2)1, V = 752.91(5) A3, Z = 1,
Dc = 1.444 g cmꢁ3, m = 2.188 mmꢁ1, F000 = 344, T = 100(2)K, 2ymax
=
66.771, 13 224 reflections collected (2563 unique), R1 = 0.0751 and wR2 =
0.1959 [I 4 2s(I)], Rint = 0.0623, GOF = 1.15.
12 S. P. Kelley, L. Fabian and C. P. Brock, Acta. Crystallogr., 2011,
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B56, 715.
Crystal data for (R)-3 (reactant): C14H17NO16S, Mr = 327.35,
Triclinic space group P1, a = 7.9008(2), b = 8.0121(2), c =
11.8061(3) A, a = 83.617(1), b = 77.774(2), g = 88.744(2)1, V =
725.87(3) A3, Z = 2, Dc = 1.498 g cmꢁ3, m = 2.269 mmꢁ1, F000
=
13 C. Dryzun, A. Zait and D. Avnir, J. Comput. Chem., 2011,
32, 2526.
344, T = 100(2)K, 2ymax = 67.571, 4857 reflections collected
c
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Chem. Commun., 2012, 48, 519–521 521