A photoreactive crystalline quasiracemate

Article abstract of DOI:10.1039/c0cc02775h

Rationally designed racemic and quasiracemic sulfonamidecinnamic acids assemble to give hydrogen-bonded dimers with coplanar alignment of neighboring olefins. The quasiracemate phase contains near inversion-related motifs with chemically distinct components forming supramolecular heterodimers that undergo asymmetric photodimerization.

Full text of DOI:10.1039/c0cc02775h

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A photoreactive crystalline quasiracematew
Rebecca C. Grove, Steven H. Malehorn, Meghan E. Breen and Kraig A. Wheeler*
Received 24th July 2010, Accepted 24th August 2010
DOI: 10.1039/c0cc02775h
Rationally designed racemic and quasiracemic sulfonamide-
cinnamic acids assemble to give hydrogen-bonded dimers with
coplanar alignment of neighboring olefins. The quasiracemate
phase contains near inversion-related motifs with chemically
distinct components forming supramolecular heterodimers that
undergo asymmetric photodimerization.
reactivity pattern align with centrosymmetrically related
components to give the expected topochemically derived
head-to-tail products (a-truxillic acids).3,10 Given the inversion
relationships of these assemblies, we envisioned that the
quasiracemic approach could present an attractive opportunity
to explore and control chemical reactivity. Moreover, since
quasiracemate construction involves heteromeric pairs of
enantiopure compounds, the application of this general
method offers promise as a facile entry point for controlling
chirality of solid-state processes.
The utility of [2+2] photochemical transformations using
molecular crystals continues to appeal to a wide range of
disciplines that seek to understand and control the reactivity of
molecular assemblies. Early success in this field can be traced
to well-defined targets resulting in predetermined reactivity1 as
well as other notable examples derived from serendipitous
routes.2 The collective effort of these investigations provided
contemporary developments to Schmidt and Cohen’s seminal
work on cinnamic acids3 and recently paved the way for efforts
that utilize the confined environments of host frameworks4
and the directionality of molecular associations5 for
programmed reactivity. Studies that seek to align pairs of
photoactive components in the solid-state have become more
commonplace in the literature. Nonetheless, extending
this work to the construction of reliable heteromeric
assemblies1a,b,6 or stereospecific transformations1c,7 remains
a considerable ongoing challenge for supramolecular chemists.
From a design standpoint, the difficulty with directing
molecules to participate in such reactions stems from the
exquisite control required to implement motif asymmetry
and the fundamental aspects of crystal cohesion.
Component selection for this study followed several key
criteria: isosteric molecular pairs that differed in handedness
(a quasiracemate), restricted conformations that resembled
molecular ‘fish hooks’, hydrogen-bonded dimers, and
favorable olefin alignment. Although the design of these
materials followed a rational plan toward predictable motifs
(Scheme 1, top), identifying potential candidates that integrate
each design element presented considerable challenges due to
complexity and interdependence of the selection criteria.
Inspiration for these reactive quasiracemic assemblies
originated from previous structural investigations of
diarylsulfonamides11 and a photoreactive rigid ‘‘U’’ shaped
naphthoic acid-derived cinnamic acid12 where both examples
displayed molecular conformations consistent with the design
requirements of this study. Modifying the core sulfonamide
framework of ref. 11 to include both cinnamic acid
(photoreactive olefin) and amino acid (chirality) functions
combined the necessary structural features to synthesize the
target sulfonamidecinnamic acids (Scheme 1, bottom).
Sulfonamidecinnamic acids 1 and 2 were easily accessed by a
cost-effective, high-throughput two-step process. While free
rotation about the sulfonamide and amino acid bonds is
possible, we anticipated this molecular framework would
adopt the critical ‘fish hook’ shape, directed by carboxyl
O–Hꢀ ꢀ ꢀO dimer formation. When X = Y (Scheme 2), the
application of this design strategy results in racemic mixtures,
whereas the use of chemically unique components (X a Y), as
in the case of 2 [i.e., (R)-CH3 and (S)-CH2CH3], create chiral
assemblies capable of generating asymmetric a-truxillic acid
photoproducts when irradiated.
Our contribution to this area combined the structural utility
of ‘fish hook’ shaped molecular olefins and quasiracemic
materials to access absolute asymmetric crystal reactions.
Quasiracemates, materials consisting of equimolar portions
of quasienantiomers, crystallize with near inversion symmetry
that mimic the packing preferences of their racemic
counterparts.8 A recent application of the quasiracemate
approach to lattice-controlled reactions involved asymmetric
polymerization of mixed crystals constructed from (R)-phenyl-
alanine- and (S)-(3-(2-thienyl)-alanine N-carboxyanhydrides).9
Desymmetrization of the packing motifs via near inversion
relationships of the components gave enantiopure isotactic
polypeptides. In principal, this strategy to induce chirality by
exploiting the packing preferences of quasiracemic materials
should also apply to other crystal transformations such as
[2+2] photodimerizations. Many examples that exhibit this
This approach to guided assembly was initially applied to
the racemic alanine derivative 1z. Colorless plate crystals of 1
Department of Chemistry, Eastern Illinois University, Charleston,
Illinois, 61920, USA. E-mail: kawheeler@eiu.edu;
Fax: +1 217 581 6613; Tel: +1 217 581 3119
w Electronic supplementary information (ESI) available: Detailed
description of synthesis, 1H-NMR, and 13C-NMR analyses. CCDC
782795–782798. For ESI and crystallographic data in CIF or other
electronic format see DOI: See DOI: 10.1039/c0cc02775h
Scheme 1 Design strategy (top) and molecular targets (bottom) for
the construction of photoreactive sulfonamidecinnamic acids.
c
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Scheme 2 Depiction of racemic and quasiracemic supramolecular
assemblies engineered for [2+2] photodimerization reactions.
were grown from an acetone solution and X-ray crystallo-
graphic assessment showed components adopting conforma-
tions with the carboxyl group of the alanine fragment
positioned directly beneath the cinnamic acid group (Fig. 1,
ꢀ
left). This compound crystallized in space group P1 with each
racemic pair organized into centrosymmetrically related
homodimers by carboxylꢀ ꢀ ꢀcarboxyl interactions (O–Hꢀ ꢀ ꢀO,
2.643 and 2.661 A) (Fig. 1, right) that further associate with
neighboring dimers via N–Hꢀ ꢀ ꢀOQS contacts. Though the
success of this discrete motif can be attributed to the cohesive
and directional properties of hydrogen bonds, both chirality
and molecular shape played key roles in spatial organization.
Extending this work to quasiracemates involved use of a
1 : 1 bimolecular compound constructed from chemically
unique sulfonamidecinnamic acids [2, X = (R)-CH3 and
Y = (S)-CH2CH3, Scheme 2]. Despite the distinct chemical
and topological properties of the –CH3 and –CH2CH3
substitutions, co-crystallization of these homochiral compo-
nents resulted in single crystals with unit cell parameters and
packing motifs nearly identical to those cited for racemic 1. It
is noteworthy to mention that the robust nature of the
hydrogen-bonded dimers and crystalline frameworks of 1 are
tolerated in quasiracemate 2 despite the imposed chemical
variations. Also, unlike 1, the supramolecular patterns
observed for quasiracemate 2 are rigorously noncentro-
symmetric (space group P1) (Fig. 2). This molecular assembly
offers an unprecedented approach to the spatial control of
molecular associations and, in our case, the control of chirality
in solid-state transformations.
Fig. 2 Crystal structure of quasiracemate 2 showing the chiral
alignment of heterodimers, spatial variation of CH3 and CH2CH3
groups, and close stacking of neighboring olefins.
exists. In addition to favorable separation of intra-dimer
olefins (Path A), similar short CQCꢀ ꢀ ꢀCQC contacts existed
between these discrete motifs via Path B. This raised the
question of whether the UV initiated reaction will proceed
by a single reaction path. If not, how would this affect reaction
outcomes? For 1, both Paths A and B yield identical racemic
photoproducts, but invoking the analogous contacts with
quasiracemate 2 would give two distinct compounds, both
homochiral, but diasteriomerically related.
Single-crystal-to-single-crystal
transformations
were
performed on crystals of 1 and 2 via the UV tail-irradiation
technique5b,13 using a 200 W Xe(Hg) arc lamp equipped with a
360 nm optical edge filter [1, lmax = 280 nm]. During UV
exposure, crystal color and morphology remained intact
providing an opportunity to investigate reaction outcomes
by X-ray crystal analysis. Periodic X-ray data collection of 1
and 2 showed photodimerization occurred exclusively by the
intra-dimer route (Path A) in reasonable yields [26 h: 72% (1)
and 61% (2)] (Fig. 3). Unutilized Path B, determined by
inspection of DF density maps of crystal structure electron
density, was somewhat surprising since the distance between
inter-dimer olefins is slightly less than Path A. One
explanation for the observed selectivity may relate to the
The novel molecular recognition profile of these systems is
well suited to investigate photodimerization reactions in
crystals. Fig. 1 (right) and 2 show the hydrogen-bonded
homodimer of 1 and heterodimer of 2 organized with parallel
alignment of neighboring cinnamic acid olefin groups
(Path A). The distance between the centers of adjacent CQC
bonds [1, 3.634 A; 2, 3.682 A] was within Schmidt’s 4.2 A
threshold for reactivity,3 thus indicating the topochemical
feasibility of conducting photoreactions with these systems.
While the close proximity of olefinic groups offered a reason-
able mode for cyclobutane formation another plausible path
Fig. 1 Crystal structure of racemate 1 showing the ‘fish hook’
molecular conformation (left) and favorable alignment of homodimers
and neighboring olefins (right).
Fig. 3 Crystal structure projection of racemate 1 (top, 72% conversion)
and quasiracemate 2 (bottom, 61% conversion) obtained after UV
irradiation for 26 hours.
c
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degree of p-orbital overlap of the reacting centers. Intra-dimer
CQC bond slip distance is considerably less [1.01 A (1) and
1.16 A (2)] than those observed for the inter-dimer contact
[1.49 A (1) and 1.59 A (2)]. This supports the idea that
geometry, not just distance, controls the outcome of chemical
transformations in molecular crystals.3a,14
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In conclusion, this report demonstrates an unprecedented
approach to regio- and stereocontrolled [2+2] photodimerization
reactions in molecular crystals. Such work is based on
rationally designed chiral sulfonamide cinnamic acids that
readily form robust supramolecular dimers via the comple-
mentary features of non-bonded contacts and molecular
shape. Construction of these hydrogen-bonded dimers using
racemic or quasiracemic molecular pairs effectively aligns
reactive centers to give cyclobutane photoproducts in
61–72% yield. In the case of quasiracemate 2, the asymmetric
crystalline environment translates to enantiopure reaction
products.
This work was supported by the National Science Foundation
(CHE-0957391 and CHE-0722547) and an EIU Council on
Faculty Research Grant. We are grateful to Prof. B. M. Foxman
for key X-ray experimental contributions (NSF CHE-0521047)
and to Profs. S. W. Daniels, C. J. Eckhardt, and B. M. Foxman
for helpful discussions.
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Notes and references
z Crystallographic data: 1 (unreacted): C12H13NO6S, M = 299.3, T =
ꢀ
100(2) K, triclinic, P1, a = 7.2052(2), b = 8.2040(2), c = 11.3088(3) A,
a = 91.461(1), b = 92.761(1), g = 90.699(1)1, V = 667.43(3) A3, Z = 2,
=
Dc = 1.489 g cmꢁ3, refls collected = 13 874, unique = 2380, (Rint
0.0200), final R indices [I > 2s]: R1 = 0.0443, wR2 = 0.1091, GooF =
1.103. 1 (reacted): C12H13NO6S, M = 299.3, T = 296(2) K, triclinic,
ꢀ
P1, a = 7.1475(1), b = 8.1722(1), c = 11.5458(2) A, a = 91.920(1),
b = 93.863(1), g = 94.634(1)1, V = 670.153(17) A3, Z = 2, Dc
=
1.483 g cmꢁ3, refls collected = 13 739, unique = 2379, (Rint = 0.0372),
final R indices [I > 2s]: R1 = 0.0449, wR2 = 0.1205, GooF = 1.048. 2
(unreacted): C25H28N2O12S2, M = 612.6, T = 100(2) K, triclinic, P1,
a = 7.3133(3), b = 8.2316(3), c = 11.5670(4) A, a = 88.171(3), b =
84.518(3), g = 86.427(4)1, V = 691.57(5) A3, Z = 1, Dc = 1.471 g cmꢁ3
,
refls collected = 6649, unique = 3209, (Rint = 0.0277), final R indices
[I > 2s]: R1 = 0.0415, wR2 = 0.1047, GooF = 1.039. 2 (reacted):
C25H28N2O12S2, M = 612.6, T = 296(2) K, triclinic, P1, a =
7.2486(2), b = 8.1094(2), c = 11.8857(3) A, a = 89.015(2), b =
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82.881(2), g = 83.670(3)1, V = 689.05(3) A3, Z = 1, Dc = 1.476 g cmꢁ3
,
refls collected = 7005, unique = 4837, (Rint = 0.0157), final R indices
[I > 2s]: R1 = 0.0434, wR2 = 0.0945, GooF = 1.016. X-Ray
diffraction data were collected on a Bruker APEX-II [1 (unreacted/
reacted), 2 (unreacted), CuKa radiation: l = 1.54178 A] and P4 CCD
[2 (reacted), MoKa radiation: l = 0.71073 A] diffractometers.
Empirical absorption corrections were applied using SADABS.15
Structures solved by direct methods and refined by full-matrix least-
squares analysis on F2 using SHELX.16 Non-hydrogen atoms
corresponding to reactant (six phenyl and two olefin C atoms) and
product (six phenyl and two cyclobutane C atoms) were located on
successive DF density maps. Percent conversion was estimated by
refinement of the occupancy factors of each phase with the sum
constrained to 1.0. CCDC 782795–782798 contain the supplementary
crystallographic data for this paper.
14 S. K. Kearsley, in Organic Solid State Chemistry, ed. G. R. Desiraju,
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corrections, University of Gottingen, Gottingen (Germany).
¨
¨
16 G. M. Sheldrick, Acta Crystallogr., Sect. A: Fundam. Crystallogr.,
2008, 64, 112.
c
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This journal is The Royal Society of Chemistry 2010