Directional cyclooligomers via alkyne metathesis

Article abstract of DOI:10.1021/ja303572k

Macrocyclic oligomers possessing direction-defining ester linkages were synthesized via metathesis of the nondirectional alkyne functional group. Alkyne metathesis is expected to scramble the relative orientation of adjacent ester groups, potentially leading to a complex mixture of macrocyclic products. We wondered whether a narrow product distribution would be achievable with a proper choice of the building block structure. Here we show that the shape of the building block determines whether the macrocyclic products are directionally uniform or scrambled. Specifically, two isomeric arylene-ethynylene polyesters afforded significantly different product distributions upon being subjected to depolymerization-macrocyclization. These results underscore the importance of learning how the shape and geometry of the building blocks affect the macrocyclization energy landscape.

Full text of DOI:10.1021/ja303572k

Communication
pubs.acs.org/JACS
Directional Cyclooligomers via Alkyne Metathesis
Scott W. Sisco and Jeffrey S. Moore*
Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United
States
S
* Supporting Information
under thermodynamic control that takes advantage of a highly
active molybdenum(VI) propylidyne catalyst6 and the reversi-
ABSTRACT: Macrocyclic oligomers possessing direction-
defining ester linkages were synthesized via metathesis of
bility of alkyne metathesis.7 This DCC method yields
the nondirectional alkyne functional group. Alkyne
metathesis is expected to scramble the relative orientation
of adjacent ester groups, potentially leading to a complex
mixture of macrocyclic products. We wondered whether a
narrow product distribution would be achievable with a
proper choice of the building block structure. Here we
show that the shape of the building block determines
whether the macrocyclic products are directionally uni-
form or scrambled. Specifically, two isomeric arylene-
ethynylene polyesters afforded significantly different
product distributions upon being subjected to depolymer-
ization−macrocyclization. These results underscore the
importance of learning how the shape and geometry of the
building blocks affect the macrocyclization energy land-
scape.
interesting macrocycles in short synthetic sequences but to
date has been tested only on simple geometries and rigid
systems.3,7 Because of the dynamic nature of alkyne metathesis
and thermodynamic control of the macrocyclic products, it
would be advantageous to generate a set of design principles for
the rational synthesis of novel target AEMs. With this goal in
mind, the reactivities of two constitutionally isomeric systems
under alkyne metathesis conditions provided insight to
understand how shape and geometry affect the thermodynami-
cally controlled product distribution (Scheme 1). Specifically,
we describe the unexpected yet significant impact the building
block shape has on the dynamic depolymerization of these two
isomeric arylene-ethynylene polyesters (MM and OP).
Polymerization8 was achieved by the self-condensation of
phenol- and carboxylic acid-functionalized tolane monomers 1
and 2 [see the Supporting Information (SI) for the syntheses of
1 and 2]. Polymerization with diisopropylcarbodiimide (DIC)
and diaminopyridinium p-toluenesulfonate (DPTS) in methyl-
ene chloride yielded polymers MM and OP, respectively, after
precipitation into methanol. Preparative gel permeation
chromatography (GPC) was used to remove low molecular
weight oligomers. The corresponding polyesters exhibited good
solubility in common organic solvents and moderate molecular
weights (MWs) of 18 and 9.6 kDa, respectively. With the
polymers in hand, we next explored their behavior under the
dynamic conditions of alkyne metathesis (Scheme 1).
Specifically, polyester MM was subjected to alkyne metathesis
using a highly active tris(amido)molybdenum propylidyne
complex with triphenylsilanol as the ligand.9 After 48 h at room
temperature, the reaction was analyzed by GPC (Figure 2 top).
The trace showed the disappearance of high MW material and a
significant increase in lower MW oligomers. Analysis of the
crude product mixture by matrix-assisted laser desorption/
ionization mass spectrometry (MALDI-MS) revealed cyclic
macrocycles from trimer to octamer. The crude depolymeriza-
tion product was purified by silica gel chromatography followed
by preparative GPC to obtain MM-[3]mer in 17% yield
(Figure 2 top). An inseparable mixture of larger cyclic species
MM-[x]mer (x > 3) was isolated in 60% yield.
ynamic covalent chemistry1 (DCC) is a powerful tool for
D
the construction of macrocyclic architectures2 from
simple building blocks. Rapid, reversible reactions under
thermodynamic control yield product distributions that are
determined by the differences in free energy of the possible
structures. To realize high yields of a single macrocyclic
product, competing structures must possess distinct differences
in molecular geometry or conformation, thereby shaping the
energy landscape3 from flat to funnelled. When building blocks
with directionality4 are involved in DCC, achieving such narrow
landscapes is especially challenging because “head−tail”,
“head−head”, and “tail−tail” connections are possible.5 In this
communication, we report on the surprising product
distributions obtained from the depolymerization of two
isomeric polymers consisting of directional ester and nondirec-
tional alkyne bonds (Figure 1).
We recently described a synthetic strategy for preparing
shape-persistent arylene-ethynylene macrocycles (AEMs)
Because of the directional nature of the ester linker, there are
n − 1 constitutional isomers for each odd-n cyclic [n]mer and
m constitutional isomers for each even-m cyclic [m]mer. For
example, MM-[3]mer has two possible constitutional isomers,
Figure 1. Directionality of functional groups. Here the nondirectional
alkyne is utilized in a DCC cyclooligomerization.
Received: April 13, 2012
Published: May 17, 2012
© 2012 American Chemical Society
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a
Scheme 1. Synthesis of Macrocyclic Oligomers
Figure 2. Top: GPC traces of MM polymer (blue), the crude
metathesis mixture (red), MM-[3]mer (purple), and the mixture of
macrocycles MM-[x]mer (green). Bottom: GPC traces of OP
polymer (black), the crude metathesis mixture (light blue), OP-
[3]mer (dark red), and OP-[4]mer (brown). The intensities have
been normalized.
a
Reaction conditions: (a) 1.5 equiv of DIC, 0.5 equiv of DPTS,
CH2Cl2, 25 °C, 24 h; (b) 10 wt % Mo Cat, 15 wt % Ph3SiOH, 1,2,4-
b
trichlorobenzene, 25 °C, 48 h. OP-[3]mer and OP-[4]mer were
isolated as a mixture. The yields were determined by 1H NMR
spectroscopy.
Figure 3. Two constitutional isomers of MM-[3]mer and the
corresponding aromatic protons.
MM-[4]mer has four possible isomers, and so forth.10 Further
analysis of MM-[3]mer predicts a 1:3 statistical mixture of
MM-A3 to MM-A2B (Figure 3), assuming no energy difference
between the two. The symmetric MM-A3 isomer is directionally
uniform, whereas the unsymmetric MM-A2B isomer displays
both ester orientations. The 1H NMR spectrum of MM-[3]mer
in CDCl3 was not well resolved in the aromatic region, but
there was considerable shifting and resolution of the peaks
when the solvent was switched to C6D6 (Figure S1 in the SI).
The MM-A3 isomer has a C3 rotation axis, so there are 7 unique
aromatic protons (a−g). In contrast, MM-A2B has 21 unique
aromatic protons (a′−g‴) because of the reduction in
symmetry (Figure 3). A 1:3 statistical mixture of MM-A3 to
MM-A2B will possess a 1:1:1:1 ratio of protons x/x′/x″/x‴ (x =
In great contrast to the depolymerization of MM, a
completely different result was observed for the depolymeriza-
tion of OP. When polyester OP was subjected to metathesis,
analysis of the crude product by GPC showed a greater shift
toward low MW material (Figure 2 bottom). In fact, only the
cyclic trimer and tetramer (OP-[3]mer and OP-[4]mer,
respectively) were observed by MALDI-MS analysis. A mixture
of OP-[3]mer and OP-[4]mer (along with triphenylsilanol)
was isolated after silica gel chromatography. Further
purification by preparative GPC allowed the isolation of the
macrocycles in a combined yield of 54%. A small amount of
each macrocycle was separated and used for identification of
1
the macrocycle peaks by H NMR analysis. The OP-[3]mer/
OP-[4]mer ratio was determined to be 2.4:1. Interestingly,
only the directionally uniform isomers were observed in the 1H
NMR spectrum (only seven aromatic protons) for both OP-
[3]mer and OP-[4]mer.11 This is remarkable, especially for the
tetramer, since the same rule applies as for the MM system,
where two constitutional isomers are possible for the cyclic
trimer (Figure 4) and four constitutional isomers are possible
for the cyclic tetramer.10
1
a−g). Comparison of the H NMR spectra of the isolated
isomeric mixture after metathesis and the pure MM-A3 isomer
isolated after polyesterification (Figure S3), along with COSY
analysis (Figure S2), allowed unambiguous assignment of most
of the peaks. More specifically, protons g and g′ display the
same integrated intensity, consistent with the 1:3 statistical
mixture of MM-A3 to MM-A2B.
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MM and OP systems highlights the need for a better
understanding of how different shapes, geometries, and degrees
of freedom affect the macrocyclization energy landscape. To
accomplish this, the synthesis of a series of structurally unique
arylene-ethynylene polymers and an investigation of their
corresponding reactivities via alkyne metathesis are currently
being pursued.
ASSOCIATED CONTENT
■
S
* Supporting Information
Figure 4. Two constitutional isomers of OP-[3]mer.
Experimental procedures and NMR, GPC, and MALDI-MS
data. This material is available free of charge via the Internet at
http://pubs.acs.org.
The two polymers MM and OP contain constitutionally
isomeric monomer units, yet their product distributions after
metathesis are drastically different. This can be explained by
examining how the shape and geometry of the MM and OP
monomer units affect the macrocyclization energy landscape.
Both MM and OP monomer units have the same 60° angle
between alkynes (Figure 5), which expectedly favors formation
of the [3]mer. However, the two monomers have different
shapes because of the positions of the substituents on the
phenyl rings. Comparison of the pair of directionally reversed
monomers reveals the MM monomer to display a congruent
shape, whereas the OP monomer displays an incongruent
shape.
AUTHOR INFORMATION
■
Corresponding Author
jsmoore@illinois.edu
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Science Foundation
(Grant CHE-1010680). The authors thank Dr. Dustin Gross
for helpful discussions relating to this project.
REFERENCES
■
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