Reactive cross-talk between adjacent tension-trapped transition states

Article abstract of DOI:10.1021/ja107645c

Tension along a polymer chain traps neighboring s-trans/s-trans-1,3- diradicals from the mechanically induced ring opening of gem- difluorocyclopropanes (gDFCs). The diradicals correspond to the transition states of the force-free thermal isomerization reactions of gDFCs, and the tension trapping allows a new disproportionation reaction between two simultaneously trapped diradicals to take place.

Full text of DOI:10.1021/ja107645c

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Reactive Cross-Talk between Adjacent Tension-Trapped
Transition States
Jeremy M. Lenhardt,† James W. Ogle,† Mitchell T. Ong,‡ Robert Choe,† Todd J. Martinez,*,‡ and
Stephen L. Craig*,†
†Department of Chemistry, Duke University, Durham, North Carolina 27708, United States
‡Department of Chemistry, Stanford University, Stanford, California 94305, United States
S Supporting Information
b
ABSTRACT: Tension along a polymer chain traps neigh-
boring s-trans/s-trans-1,3-diradicals from the mechanically
induced ring opening of gem-difluorocyclopropanes
(gDFCs). The diradicals correspond to the transition states
of the force-free thermal isomerization reactions of gDFCs,
and the tension trapping allows a new disproportionation
reaction between two simultaneously trapped diradicals to
take place.
e recently reported that the tension along a polymer main
chain can be used to trap species that are at or very near the
W
transition state of a chemical reaction,1 namely, the s-trans/
s-trans-1,3-diradicals that form during the isomerization of 2,3-
disubstituted gem-difluorocyclopropanes2,3 (gDFCs) on polybu-
tadiene (PB) scaffolds. The underlying reactivity is shown in
Figure 1. The thermal activation of a trans-gDFC proceeds in a
formally disrotatory process to the s-cis/s-trans diradical transi-
tion state, which undergoes ring closure by the same mechanism
to regenerate the trans-gDFC (Figure 1a). An analogous process
occurs for cis-gDFCs, but the transition-state structure is the
s-trans/s-trans diradical (Figure 1b). Applying a large mechanical
force through sonochemical shear fundamentally changes the
potential energy surface, causing the ring opening to proceed in a
conrotatory fashion to the s-trans/s-trans diradical, which, despite
being the transition state of a thermal reaction,2,3 is a global
minimum on the force-coupled potential energy surface. Once
the transient shear event ends, the diradical closes in the normal,
force-free disrotatory manner to the cis isomer. Here we report
that large numbers of these diradicals can be trapped simulta-
neously and in proximity to each other, enabling a new fragmen-
tation reaction between two diradicals to take place.
Figure 1. Thermally, both (a) trans- and (b) cis-gDFCs preferentially
open and close through a disrotatory process via a 1,3-diradical transi-
tion state. (c) Application of a large mechanical force leads to the
formation and trapping of the s-trans/s-trans-1,3-diradical “transition
state”, which closes to the cis-gDFC once the force is removed.
was determined from multiangle light scattering (MALS) gel-
permeation chromatography (GPC). Critical for the work re-
ported here is that both isomerization and scission of the polymer
were observed; for convenience, we define φ1 to be the fraction of
trans-gDFCs that isomerize during the first scission cycle.
Normalizing the extent of isomerization in terms of the scission
cycle is a robust and convenient mechanism to account for
variations in the magnitude of the forces generated as a result of,
for example, polymer molecular weight, gDFC content, and
fluctuations in sonication power.6 We note that the variation in
absolute polymer scission rates was much too small to account
for the differences reported here (see the SI).
In the random gDFC copolymers, higher gDFC content gave
lower levels of isomerization (Figure 2). For example, φ1 = 0.41
and 0.19 for copolymers of 97 kDa/3.8% gDFC and 88 kDa/59%
gDFC, respectively. The inverse dependence of isomerization
rate on copolymer loading was observed for polymers with
gDFC loadings of up to 95%, spanning φ1 from 0.07 to 0.41
(Figure 2c).
In our previous study, well over 100 trans-gDFC isomerization
reactions were typically observed to occur by the time the
polymer Mn was cut in half [i.e., in one scission cycle; see the
Supporting Information (SI)] in a competing mechanochemical
process.1 Unexpectedly, however, the extent of isomerization
depends on the gDFC content of the copolymer (Figure 2),
which was prepared by difluorocarbene addition to cis/trans-PB
using known methods.4,5 The mechanical activation of gDFCs
was induced by pulsed ultrasound (11.3 W cm-2) in an ice water
bath (6-9 °C) under an inert N2 atmosphere and monitored by
19F NMR spectroscopy, and the molecular weight degradation
The decrease in isomerization efficiency with increasing gDFC
incorporation suggested participatory effects of neighboring ring-
Received: August 24, 2010
Published: February 22, 2011
r
2011 American Chemical Society
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Figure 3. (a) Proposed mechanism for the force-induced fractionation
of neighboring 1,3-diradicals; P denotes the polymer chain. (b) Extent of
trans-to-cis isomerization efficiency at one scission cycle (φ1) as a
function of P*.
in the extension event, as proposed in Figure 3a, is proportional
to the absolute number of adjacent gDFCs in the mechanically
active zone of the polymer, the size of which is in turn propor-
tional to the degree of polymerization (DP). Importantly, the
isomerization efficiencies correlate almost perfectly with P* =
Figure 2. (a, b) Ring-opening metathesis polymerization yields (a)
polymer 1 (33.3% gDFC) and (b) polymer 2 (66.7% gDFC). (c)
Fraction of trans-gDFC converted to cis-gDFC as a function of difluor-
ocarbene addition to PB. Points are experimental values taken from 19
F
PFF DP (Figure 3b) as opposed to PFF alone (Figure S94 in the
NMR integrations and have an estimated uncertainty of (3%. Lines are
linear fits constrained through the origin and are used to extrapolate the
% isomerization to one scission cycle.
3
SI). These analyses included polymers of varying molecular
weights, gDFC content, and controlled gDFC microstructure
(including polymer 2 in Figure 2b) beyond those for which data
is shown in Figure 2c (Table S1 in the SI). Additional experi-
opened 1,3-diradicals along the polymer backbone. This was
confirmed by ring-opening metathesis polymerization (ROMP)
of a mono-gDFC-cyclododecatriene to yield a 66 kDa copolymer
with 33.3% trans-gDFC content and no adjacent gDFCs
(Figure 2a, polymer 1). Sonication of 1 led to the highest
normalized extent of isomerization, over twice that of an
equivalently functionalized random copolymer (319 kDa, 32%
gDFC-PB).
mental support for the mechanism was provided by 1H and 19
F
NMR spectroscopy of the reaction products generated by the
sonication of 95% gDFC-PB. The chemical shifts and coupling
patterns of new resonances in the 1H and 19F NMR spectra agree
with those of model compounds with terminal 3,3-difluoroalk-
enes, and the relative intensities of the new peaks are consistent
with the 3,3-difluoroalkenes being the dominant product of chain
scission (Figures S81-S93).
An alternative explanation is that a weak bond is created
simply by generating one diradical next to an intact cyclopro-
pane. To address this possibility, a 36% gDFC-PB was reacted
with dichlorocarbene to yield a mixed gDFC-gDCC-PB poly-
mer with 36% gDFC and 26% gDCC content. The 36% gDFC
polymer had the same φ1 value (0.20) with or without the added
gDCCs. Much stronger support was provided by ab initio steered
molecular dynamics (AISMD) calculations under simulated
force.1,11 The AISMD simulations confirmed that once one
gDFC opens to the diradical, the ring opening of an adjacent
gDFC precedes bond scission between the open diradical and
closed gDFC (Figure 4). A total of 20 trajectories were run on
gDFC dimers (cis,trans) under simulated forces of 3 nN. The
mixed cis,trans dimers were chosen to confirm that both isomers
open prior to bond scission and that the subsequent reactivity is
independent of the initial stereochemistry because both isomers
generate the same diradical.1
A likely explanation is that as the polymer is stretched under
tension, the peak force along the polymer backbone increases
and more and more gDFCs are pulled into the diradicals that
correspond to force-free transition states. Both the peak force
and activated zone continue to grow until the polymer snaps,
halting subsequent gDFC activation. This picture of multiple
transformations occurring in a single extension event is consis-
tent with our earlier observations on the related mechanical
activation of gem-dichlorocyclopropanes (gDCCs) under similar
conditions.7 The influence of neighboring gDFCs would then be
explained by the mechanism shown in Figure 3a. Activation of
adjacent gDFCs leads to a tetraradical that disproportionates at a
lower force than the rest of the polymer backbone, halting the
mechanical activation prematurely.
Bernoullian statistical analysis8 supports this picture. The
probabilities of adjacent gDFCs [PFF = (% gDFC)2] were
calculated assuming a random distribution of gDFCs. The
probability of generating and breaking a weak bond at any point
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For example, from the Bell-Evans theory, k(F) = rF/fβ, where rF
is the loading rate and fβ describes the characteristic force
dependence of the rate constant [the inverse slope of a plot of
ln k(F) vs F].10 Use of the fβ value for Si-C bond scission, which
has been previously reported to be ∼102 pN,9 suggests that the
force should continue to build until the rate of bond scission is
>108 s-1. (It should be noted that we provide this analysis for
rough “order of magnitude” purposes of discussion only. We
recognize that many questions exist regarding the specific
dynamics of loading and reaction. Nonetheless, we regard this
estimate as a likely lower limit for the case at hand.)
In the simulations, two out of 20 dimers broke in 1 ps at 3 nN,
meaning that the rate constant of the chain scission reaction at 3
nN approaches 1012 s-1. On the basis of the discussion above, the
typical peak force for chain scission is therefore likely less than 3
nN, but not dramatically so. Because ring opening is much faster
than chain scission at both zero force (thermal isomerization of
the gDFCs was observed without chain scission1) and 3 nN,
however, we infer that the same relative reactivity observed in the
simulations applies to the experimental conditions. The AISMD
simulations are therefore consistent with a mechanism in which
adjacent diradicals are formed prior to bond scission, which
subsequently occurs at the site proposed in Figure 3a.
In conclusion, tension trapping allows the reactivity between
two diradicals that closely resemble the transition states of force-
free reactions to occur. This mode of reactivity represents a new
method by which to engineer covalent mechanochemistry in
polymers and polymeric materials. In addition, the use of
mechanical force to characterize the chemistry of species whose
existence is otherwise fleeting expands its application as a tool for
physical organic chemistry, as applied previously in strained
macrocycles12 and in the sonochemically directed anti-Wood-
ward-Hoffmann ring-openings of benzocyclobutene13 and the
gem-difluorocyclopropanes discussed here.1 With the increasing
interest in the synthesis of new mechanophores and the char-
acterization of their behavior in severe stress fields,14-18 we
anticipate that numerous challenges to conventional notions of
reactivity will continue to appear.
Figure 4. (a) Representative time points taken from an AISMD
simulation of a gDFC dimer under a simulated force of 3 nN. The
dominant process is ring opening of the gDFCs into their respective 1,3-
diradicals, which occurred in all 20 simulated trajectories, as shown in the
snapshots at 100 and 200 ps of simulation time. In two out of 20
trajectories, including the one shown here, a secondary bond scission
process occurred, giving alkene-terminated products. (b) Bond lengths
associated with gDFC ring opening and bond scission as functions of
time for the MD simulation corresponding to (a).
’ ASSOCIATED CONTENT
S
Supporting Information. Details of syntheses, character-
b
ization data, NMR spectra, and details of molecular dynamics
simulations. This material is available free of charge via the
Internet at http://pubs.acs.org.
In all 20 trajectories, the primary process was ring opening;
both gDFCs rapidly and irreversibly formed the associated
diradicals before any bond scission reaction was observed. In
18 of the trajectories, the adjacent diradicals remained intact for
the 1 ps duration of the simulation. In two of the 20 trajectories,
however, the adjacent diradicals disproportionated via the me-
chanism shown in Figure 3a. The simulated force of 3 nN was
probably an overestimate of the peak force in the sonication
experiments, as suggested by the following analysis. Similar
sonication conditions lead to covalent bond scission in PB and
other covalent polymers,7 a process that requires several nano-
newtons of force9 to build on the approximately microsecond
time scale of bubble collapse. Dividing the change in the force by
the time scale of collapse gives a lower limit (full extension and
chain scission may not require the full time of the bubble
collapse) of ∼1010 pN s-1 for the effective loading rate of force
during extension. The force builds until the rate of force-
accelerated chain scission is comparable to the loading rate.
’ AUTHOR INFORMATION
Corresponding Author
todd.martinez@stanford.edu; stephen.craig@duke.edu
’ ACKNOWLEDGMENT
This material is based upon work supported by the U.S. Army
Research Laboratory and the U.S. Army Research Office under
Grant W911NF-07-1-0409. J.M.L. was supported by the ACS
Division of Organic Chemistry Schering-Plough Fellowship.
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