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org/JACS Article

Understanding and Enhancing Stereoselective Polymerization Using

a Data Science Approach
Caleb T. Kozuszek, Cole C. Sorensen, and Frank A. Leibfarth*
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ABSTRACT: Controlling the tacticity of synthetic polymers

results in the transformation of simple chemical building blocks
into valuable materials with emergent physical properties.
Mechanistic insight into stereoselective polymerizations enables
hypothesis-driven improvements to catalysts and gives access to
polymers with systematic differences in tacticity for structure−
property studies. Studying the mechanism of stereoselective
polymerization, especially of heteroatom-containing monomers
that polymerize through ionic intermediates, is hindered by the
challenges of using traditional physical−organic or computational
approaches. Here, we use a combination of experiments and
computationally derived molecular descriptors to identify quantitative relationships between catalyst structure and stereoselectivity
through a data science approach. Stereoselective polymerization of benzyl vinyl ether derivatives with a structurally diverse library of
imidodiphosphorimidate (IDPi) catalysts resulted in 40 experimental data points, which were correlated to computationally derived
molecular descriptors by using multivariate linear regression analysis. The regression model identified the dihedral angle of the 1,1’-
binaphthyl-2,2’-diol (BINOL) subunit of the IDPi to be strongly correlated to isotacticity, which led us to reconsider the long-
standing hypothesis for the conformation of the propagating polymer chain-end during cationic vinyl ether polymerization. We
anticipate that the specific insights of this study will inform the next generation of catalysts for stereoselective cationic polymerization
and that the data-driven approach to understand the mechanism for stereoselective polymerizations demonstrated herein will be an
invaluable tool in catalyst design and discovery for polymer chemistry broadly.

■ INTRODUCTION
Stereoselective cationic polymerization of vinyl ethers is a
generate the level of mechanistic understanding required to
engage in hypothesis-driven catalyst design.21 An analogy can
powerful strategy for the synthesis of semicrystalline thermo- be made to early work in coordination−insertion polymer-
plastics from a simple and readily available polar monomer ization, where the challenge of understanding the mechanism
feedstock. Contemporary approaches leverage asymmetric ion- of heterogeneous catalysts hindered the realization of materials
pairing (AIP) catalysis to bias the facial addition of monomer with high tacticity and advanced microstructures. The
to the prochiral oxocarbenium chain-end using a chiral discovery of homogeneous catalysts activated by methylalumi-
counteranion.1−3 Several groups have used AIP catalysis with noxane (MAO)22,23 enabled detailed mechanistic studies that
both chiral Lewis acid and Brønsted acid catalysts to synthesize led to poly(α-olefins) with tunable tacticity, microstructure,
isotactic poly(vinyl ether)s that are semicrystalline, polar and architecture, which are found in numerous commercial
thermoplastics with a desirable combination of adhesion and products.24
mechanical properties otherwise unavailable from their atactic An acute challenge in identifying catalyst structure−
equivalents (Figure 1A).4−19 stereoselectivity trends for cationic polymerization is the
Despite recent advancements in stereoselective cationic inability to use many traditional physical−organic approaches
polymerization, state-of-the-art catalysts struggle to achieve to probe reaction mechanisms.1 For example, the two-state
high selectivities (>90% meso diads (% m)) and have a limited model required to interpret kinetic isotope effect (KIE) and
substrate scope. These limitations are a direct result of the
rudimentary understanding of catalyst design principles that
engender high selectivity. This is partially due to the empirical Received: June 27, 2025
approach to catalyst/substrate optimization that remains the Revised: November 23, 2025
standard in the field of stereoselective polymerization.20 Accepted: November 25, 2025
Catalyst screening efforts undertaken during empirical
optimization can result in catalyst discovery, but they struggle
to identify discrete structure−stereoselectivity trends that
© XXXX The Authors. Published by
American Chemical Society [Link]
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function.37−39 In polymer chemistry as a whole, data-driven

approaches to understand polymerizations are nascent.40−45
The key example of a data-driven approach for polymerization
catalyst design uses Bayesian optimization to predict high-
performing catalysts for stereoselective ring-opening polymer-
ization of lactide based on data-mined literature values.46
Herein, we reveal unanticipated structural features of IDPi
catalysts that correlate with tacticity and revise the long-
standing hypothesis for the conformation of the propagating
polymer chain-end during cationic vinyl ether polymerization
using a data-driven approach. Stereoselective polymerization of
benzyl vinyl ether derivatives with a structurally diverse library
of IDPi catalysts resulted in 40 experimental data points, which
were correlated to computationally derived molecular
descriptors using MVLR (Figure 1B). The regression model
identified a structural attribute of the catalyst�the dihedral
angle of the 1,1’-binaphthyl-2,2’-diol (BINOL) scaffold�as
strongly correlated to stereoselectivity. This nonintuitive
insight gained from the application of MVLR inspired
additional analysis, the outcomes of which are: i) a hypothesis
for how IDPi catalysts engender stereoselectivity during vinyl
ether polymerization, ii) a revision of the prevailing hypothesis
for the proposed conformation of the propagating polymer
chain-end during cationic vinyl ether polymerization, and iii) a
library of isotactic, semicrystalline poly(benzyl vinyl ether)s
that combine the crystallinity of stereoregular polymers with
Figure 1. (A) Development of polar, isotactic poly(alkyl vinyl ether)s the degradability of heteroatom-rich materials.
has largely depended on the empirical optimization of Lewis acid or
Brønsted acid catalysts. (B) Data science gives mechanistic insight
into the stereoselective cationic polymerization of benzyl vinyl ethers. ■ RESULTS AND DISCUSSION
Our studies began by evaluating a library of IDPi catalysts for
the polymerization of benzyl vinyl ether to yield poly(benzyl
linear free energy relationship (LFER) experiments breaks vinyl ether) (PBnVE) (Figure 2). Polymerizations were
down in polymerization because each propagation represents a performed in toluene at −78 °C and demonstrated kinetics
bifurcation of the potential energy surface, leading to 2n (where commensurate with uncontrolled chain growth polymerization,
n = number of repeat units) possible diastereomeric transition where initiation is slower than propagation, chain transfer and
states.25−30 Additionally, the rapid rate of cationic polymer- early termination are prevalent, and molar mass is high even at
ization, even at low temperatures (−78 °C), presents a low conversions.47,48 Tacticity was measured by integration of
practical challenge by obfuscating reaction and intermediate the backbone methylene resonance in the 13C NMR (see
monitoring. The use of density functional theory (DFT) is a Supporting Information for details).49 As a benchmark for an
complementary method to gain insight into reaction atactic polymer, triflic acid (TfOH) was used as a catalyst and
mechanisms; however, the challenge of managing the produced PBnVE with an isotacticity of 68% m. For TfOH, we
speciation of relevant intermediates and the conformational attribute the small isoenrichment to chain-end (i.e., substrate)
flexibility of a polymer chain makes these computations control of selectivity.50 For IDPi catalysts, structural variations
expensive.1 included the aryl substituent at the 3,3′-position of BINOL and
Data-driven approaches for mechanistic analysis have the electron-withdrawing substituent on the sulfonimide. IDPi
successfully been applied in small molecule asymmetric substitutions were selected due to chemical similarity to
catalysis, where experimental data and computationally derived previously successful IDPi structures used in cationic polymer-
physical−organic descriptors can be correlated using ap- ization,6,7,19 proximity to highly successful IDPi structures used
proaches such as multivariate linear regression (MVLR) in small molecule catalysis,51−59 and broad structural diversity
analysis. The outcome is quantitative correlations that connect within the catalyst scope. Previously, the 3,5-bis-
molecular features of a catalyst or substrate to stereoselectivity (trifluoromethyl)phenyl group at the 3,3′-position of BINOL
and reveal mechanistic insights that are otherwise challenging has been shown to be privileged for stereoselective cationic
to identify through inspection.31−35 This workflow has proven polymerization.5−7,19 Accordingly, polymerization with cata-
especially useful to investigate high-energy, difficult-to-study lysts 1a−f resulted in PBnVEs with isotacticities >80% m, with
intermediates where small changes in relative transition state differences related to the sulfonimide substituent. Catalysts
energy are difficult to model, which was recently exemplified bearing perfluoroalkyl substituents (1b−e) at the sulfonimide
for enantioselective C−H insertion reactions of vinyl cations performed very similarly, with selectivities ranging from 88 to
mediated by imidodiphosphorimidate (IDPi) catalysts.36 90% m, while the perfluorophenyl substituent 1f demonstrated
Stereoselective polymerization presents an exciting use case the highest selectivity of 93% m. In all cases, the catalysts
for data-driven mechanistic studies and catalyst design. Small bearing other substitutions at the 3,3′-position of BINOL (i.e.,
changes in tacticity from 80 to 100% m have large impacts on catalysts 2−7) underperformed compared to catalysts with the
polymer properties; therefore, mechanistic understanding that 3,5-bis(trifluoromethyl)phenyl substituent. In particular, cata-
leads to improved catalysts has a direct impact on material lyst 4b performed worse than the analogous structure in 1b,
B [Link]
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Figure 2. Polymerization of benzyl vinyl ether with a library of IDPi catalysts. Conditions: 0.1 M BnVE in toluene (MePh), quenched with 5% TEA
in MeOH. Number-average molar mass (Mn) and dispersity (Đ) obtained by size exclusion chromatography (SEC) in THF and reported based on
a calibration with polystyrene standards; tacticity obtained by 13C NMR. Number-average molar mass (Mn) is reported in kg/mol.

indicating that the presence of CF3 groups on the aryl deficient aromatic ring. Benzyl vinyl ether with a para-methoxy
substituent alone is not sufficient to engender selectivity. The substituent showed no polymerization in the presence of the
fluorene-substituted BINOL-based catalysts 6b and 7c were IDPi catalyst, likely due to the nucleophilicity of the electron-
evaluated due to the privileged status of the fluorenyl rich aromatic ring.62 Notably, low number-average molar
substitution in IDPi catalysis for stereoselective transforma- masses (Mn) were achieved with the 1-naphthyl- and 2-
tions,58 but these catalysts provided polymers with lower naphthyl-derived monomers, likely due to polymer precip-
selectivity than PBnVE made with TfOH. itation (i.e., poor solubility) observed during the polymer-
Next, we sought to understand the effect of the monomer ization. Due to the incompatibility of poly(benzyl vinyl ether)s
structure on stereoselectivity for isotactic PBnVEs. A small with group IV Lewis acid catalysts, this substrate scope
series of substituted benzyl vinyl ether monomers were represents an expansion in stereoselective cationic polymer-
polymerized using catalyst 1c (Figure 3), which represents a ization that is inaccessible to previously reported titanium
high-performing catalyst with a broad substrate scope. catalysts.63
Electron-neutral and -withdrawing groups at the para position The evaluation of structurally diverse catalysts and
of the benzyl vinyl ether monomer led to highly isotactic monomers, found in Figures 2 and 3, respectively, resulted
polymers, and electron-withdrawing groups at the ortho in 40 polymerizations with selectivities ranging from 52 to 93%
position were also well tolerated. Notably, 2-nitrobenzyl vinyl m (see Supporting Information for details). Despite this rich
ether furnished polymers with moderate isotacticity and high data set, we were unable to identify discrete structure−
number-average molar mass (83% m, Mn = 35.0 kg/mol). This stereoselectivity relationships through inspection. We turned
monomer is of particular interest because 2-nitrobenzyl groups to more quantitative approaches to identify nonintuitive
are photolabile, which may permit the use of this monomer as structural or physical−organic attributes of the catalysts and/
a vinyl alcohol synthon in a postpolymerization modification or monomers that correlate with isoselectivity. Previously,
strategy.60,61 Tong and coworkers reported the Bayesian optimization of
Bulky groups at the para position, as well as extended π- catalyst structures for stereoselective ring-opening polymer-
conjugation, were tolerated in polymerization but showed ization of lactide with a data set of 56 literature-mined data
diminished stereoselectivity. A larger decrease in selectivity was points.46 Sigman, Moore, and coworkers generated a kernel
observed with the pentafluorobenzyl vinyl ether monomer, ridge regression model with a much larger data set to predict
potentially due to the inverted quadrupole of the electron- front rate in frontal ring-opening polymerization (FROMP)
C [Link]
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optimization and frequency calculations were performed at the

b3lyp(gd3)/6−31g(d,p)/cpcm(toluene) level, and single-
point energy calculations were performed at the wb97x-d/6−
311++g(d,p)/cpcm(toluene) level of theory. The lowest-
energy conformer for each molecule was used as the ground-
state geometry for parametrization. Measured tacticities (i.e.,
stereoselectivities) from 13C NMR integration were converted
to ΔΔG‡ in kcal/mol with the modified Eyring equation:
i %m zy
G‡ = RT lnjjj zz
k %r {
From the DFT data, 56 structural, electronic, and geometric
parameters were extracted and correlated to the 40
experimental selectivity values through a forward stepwise
regression method using code developed by the Sigman lab
(Figure S1).65 An 80:20 train:test split was used with a normal
distribution of points, and parameters that were collinear (i.e.,
correlated to one another with an R2 greater than 0.50) were
removed to prevent overfitting. MVLR models of three
variables or less were investigated to maintain a >10:1 ratio
of experimental data points to variables, thereby limiting the
possibility of overfitting. The “best” model was defined as the
equation with the greatest sum of both R2 and test-R2. For the
best model, leave-one-out (LOO) and k-fold (4-fold) analysis
provided values above 0.8, indicating a robust MVLR fitting.
The forward stepwise regression yielded multiple models with
good (>0.8) correlations and robust statistics. The best-
performing model yielded an R2 = 0.891, mean absolute error
(MAE) = 0.05 kcal/mol, and R2test = 0.904, as shown in Figure
4A. These statistical values would be considered on the upper
end of fit quality based on previous MVLR models.66−74
Notably, our attempt to generate a model to correlate the
molar mass and dispersity with the set of molecular descriptors
was unsuccessful.
To demonstrate the predictive capabilities of the model, a
catalyst not represented in the data set was selected and used
for the polymerization of 4-phenylbenzyl vinyl ether (Figure
Figure 3. Polymerization of benzyl vinyl ether derivatives and their
4B). The model predicted a ΔΔG‡ value of 0.355 kcal/mol,
resultant selectivity. Conditions: 0.1 M BnVE in MePh, quenched corresponding to a tacticity of 71% m. The experimentally
with 5% TEA in MeOH. aCatalyst 5b was used. bCatalyst 2b used. Mn measured tacticity was 69.8 ± 0.6% m (ΔΔG‡ = 0.325 kcal/
and Đ obtained by SEC in THF and reported based on a calibration mol). These values are within the MAE of 0.05 kcal/mol,
with polystyrene standards; tacticity obtained by 13C NMR. Mn is illustrating the model’s predictive capabilities for BINOL-based
reported in kg/mol. IDPi catalysts.
From the MVLR model, the variable that impacts selectivity
and used Shapley analysis to uncover the contribution of most significantly is the dihedral angle (DIH) about the 2,1−
different parameters to reaction output.40 We prioritized the 1’,2’ bond in the chiral BINOL scaffold of the catalyst,
use of an interpretable approach in order to uncover physically representing 67% of the variance in selectivity (φ in Figure
significant parameters that affect the reaction output. Addi- 4A). The other catalyst parameter relevant for selectivity was a
tionally, the approach needed to be applicable for small- to steric parameter (i.e., Bmin,Ar value, Sterimol)75 measured at the
medium-sized data sets, as opposed to more data-hungry aryl substituent at the 3,3′-position of the BINOL, representing
techniques.31,64 We hypothesized that we could then use the 21% of the variability. The polarizability (POL) of the
physically significant descriptors as a starting point to better monomer accounted for 12% of the remaining variance. The
understand the selectivity−determining parameters in cationic choice to model the entire IDPi catalyst was enabling for the
polymerization. discovery of the DIH parameter. Truncated structures
We next initiated a campaign to generate a set of ground- involving one BINOL, which were used in previous work,36
state molecular geometries of the catalysts and monomers would have excluded structural contributions from the 3D
through DFT. Based on these geometries, we intended to conformation of the IDPi catalyst, making it challenging to
obtain a set of molecular descriptors that would allow us to differentiate between IDPi catalysts with the same aryl
correlate structural features of the molecules with stereo- substitution (e.g., 1a−f or 2b−c).
selectivity. Structures of the monomers and IDPi catalysts were While DIH had the largest influence on stereoselectivity
subjected to conformer searching using molecular mechanics, according to the model, a physical explanation for this strong
followed by DFT geometry optimization of the resulting correlation was not immediately apparent. A careful study of
conformers (see Supporting Information for details). For DFT, the three-dimensional DFT ground-state structure revealed a
D [Link]
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site). This observation is opposite to what has been reported in

small molecule nucleophilic addition to oxocarbenium ions,
where catalysts with highly confined Brønsted acidic sites (i.e.,
IDPi 2b, 6b, 7c) result in high enantioselectivity with small,
unbiased substrates.59 In order to gain further insight into this
observation, we set out to computationally model the ion pair
between the deprotonated catalyst and the cationic chain-end.
A cationic 6-membered chelate structure for a trimer of benzyl
vinyl ether was modeled based on a theorized intermediate for
cationic polymerization of vinyl ethers proposed by Cram and
Kopecky in 1959,76 and it was compared to a linear
oxocarbenium ion (Figure 5B). We found that the 6-
membered chelate, as a formal oxonium, is 7.3 kcal/mol
lower in energy than the linear chain-end model. Another 6-
membered chelate, where stabilization occurs due to an n→π*
interaction of the penultimate ether with the chain-end
oxocarbenium (as opposed to a formal oxonium), is within 1
kcal/mol of the oxonium chain-end (Figure 5B). For either
case, the cyclic intermediate is considerably more stable than
the linear conformation, which led us to modify our hypothesis
regarding the identity of the propagating chain-end to the 6-
membered Cram chelate as a starting point to model the ion
pairs.
The ion pairs for IDPi 1f and IDPi 7c�the highest and
lowest selectivity catalysts, respectively�and the proposed
cationic chain-end are shown in Figure 5C as electrostatic
potential (ESP) maps. The anion of IDPi 1f is more accessible,
given the large spacing between aryl groups, which leads to a
short ion pair distance of 6.8 Å and high directionality in the
displayed ESP map. The anion of IDPi 7c is less accessible,
given the small spacing between aryl groups and the larger
sterics of the fluorene-derived aryl group, which does not allow
the cationic chain-end to associate as closely and pushes the
ion pair further apart to 7.3 Å. We hypothesize that the tighter
ion pair and increased directionality77 provided by the anion of
IDPi 1f lead to a more structured transition state that helps to
bias monomer facial addition, whereas the longer distance
between the anion of 7c and the chain-end, as well as lower
Figure 4. (A) Multivariate linear regression of the polymerization anionic directionality, leads to more conformational flexibility,
data set reveals a strong correlation between selectivity and catalyst potentially encouraging nonselective pathways. This hypoth-
geometry, catalyst sterics, and monomer polarizability. Parameter esis is consistent with the inclusion of Bmin,Ar for the 3,3′-
coefficients are normalized. (B) Model validation with a new catalyst substituent on the BINOL scaffold and POL of the monomer
structure supports the predictive capability of the model for catalysts in the selectivity model. These variables indicate that catalysts
outside of the data set (experimental data obtained in quadruplicate, with sterically larger substituents on the BINOL scaffold and
presented as an average with 95% confidence interval). larger monomers decrease the selectivity. We hypothesize that
this is due to the aryl substituent’s role in catalyst confinement
potential relationship between the DIH parameter of the near the Brønsted acidic site and greater monomer size
BINOL scaffold and the distance between the aryl groups that contributing to substrate exclusion. This also serves to explain
surrounded the Brønsted acidic site of IDPi (Figure 5A). the poor performance of catalyst 1a relative to catalysts 1b−f
Quantitative evaluation of this observation was completed as a result of the −CF2H sulfonimide substituent’s tendency to
through a univariate regression analysis of increasing DIH and decrease “cavity size” around the Brønsted acid, as reported in
increasing distance between the ipso carbon atoms of the aryl the literature.57
substituents (3,3′-position on BINOL), which led to a We sought to investigate the tacticity-induced properties of
reasonable correlation of R2 = 0.71 (Figure S4). This aryl isotactic PBnVE. Increasing isotacticity is known to correlate
group spacing is not as strongly correlated with selectivity as with increasing crystallinity for poly(vinyl ether)s,5,6,78 but our
the DIH parameter and therefore did not result in a revision of ability to synthesize systematically different tacticities of
the MVLR model, which may be due to DIH capturing PBnVE allowed a more complete study of the relationship
additional three-dimensional information related to the between tacticity and crystallinity (Figure 6A). Atactic PBnVE
Brønsted acidic site. with 68% m, synthesized using TfOH as a catalyst, was
Closer inspection of the correlation between the distance amorphous, as determined in the second heating cycle of the
between aryl groups and tacticity revealed that stereocontrol differential scanning calorimeter (DSC). Increasing the
was higher for catalysts with a larger distance between aryl isotacticity to 82% m provides a weakly crystalline polymer
groups (i.e., less confinement around the Brønsted acidic active with a cold crystallization peak on the heating curve of the
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Figure 5. (A) An indirect relationship between the catalyst dihedral angle and the size of the cavity around the Brønsted acid. (B) A proposed
chain-end conformation. (C) A mechanistic hypothesis for the role in selectivity for the macromolecular system.

DSC before a weak melt transition. The 86−93% m polymers displayed rapid early degradation and a significant change in
showed melt transitions with a higher enthalpy of melting and molecular weight distribution (Figures 6C and S11−S16),
no cold crystallization, indicative of faster crystallization similar to the atactic polymer (Figure S12). Notably, the
kinetics and longer chain segments without defects that can polymer showed a rapid increase in low and high molecular
crystallize. The presence of a melting temperature (Tm) above weight species, indicating that chain scission and chain
140 °C is similar to that of high-density polyethylene, which is coupling events were both occurring. The SEC distribution
attractive for a semicrystalline polymer. The 93% m sample had broadening was observed as a decrease in Mn over time and
a slightly lower melting temperature compared to that of the increase in Đ. In comparison, polymers stored away from light
89% m sample, which is not intuitive. We hypothesize that it showed minimal reduction in molar mass (Figures S13 and
could be due to the influence of a structural feature (e.g., S14), with polymer stored under vacuum displaying virtually
microstructure) not captured by the single tacticity measure-
no change (Figure S14). Degradation of polymers through H
ment. Despite this, the whole of these insights emphasizes the
atom transfer at alkyl vinyl ether pendant groups and
importance of precise control of tacticity because a 4% meso
subsequent β-scission has been reported by the Ouchi and
diad difference (82% m to 86% m) alters crystallization
kinetics, which has implications on material performance and Stache groups previously.79,80 We hypothesize that a similar
processing. mechanism is operative due to the low predicted bond
In addition to the thermal properties associated with dissociation energy of benzylic ether C−H bonds (82 kcal/mol
stereoregularity, isotactic PBnVE displays degradability asso- by ALFABET),81,82 combined with the necessity of light and
ciated with polar, heteroatom-containing polymers. PBnVE at atmospheric oxygen for the degradation (Figure S13).
high (91% m) tacticity was synthesized and subjected to Correlative evidence for benzylic C−H oxidative cleavage
degradation under mild conditions (Figure 6B). The polymer includes the broadening of molecular weight distribution upon
was stored in the solid state in standard glass vials and degradation (Figure S15) and detection of aldehyde by-
irradiated with cool white LEDs under a cooling fan (see the products by NMR (Figure S17). Reduction in tacticity was also
Supporting Information for details). The 91% m polymer observed (91% m starting, 75% m degraded), which may be the
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Figure 7. (A) A postpolymerization modification approach for

poly(benzyl vinyl ether-co-vinyl alcohol). (B) IR spectra of the
deprotected copolymer show alcohol functional groups. (C) SEC
indicates minimal change in molecular weight distribution before and
after irradiation.

indicated complete disappearance of the 2-nitrobenzyl pendant

group (Figures S20 and S21). FT-IR displays a clear O−H
stretch in a broad peak from 3200 to 3600 cm−1 after
Figure 6. (A) DSC thermograms demonstrate the correlation irradiation, indicating that alcohol moieties are present in the
between tacticity and crystallinity in poly(benzyl vinyl ether); the deprotected material (Figure 7B). SEC suggests that the
data shown is taken from the second heating cycle at a scan rate of 10 molecular weight distribution is largely unchanged after
°C min−1. (B) Degradation of PBnVE under white light irradiation in irradiation (Figure 7C). The deprotected material also
an ambient atmosphere at ambient temperature. (C) A longitudinal
displayed a melt transition similar to the original copolymer,
study that tracked Mn and dispersity of isotactic PBnVE films under
visible light exposure over weeks. with slower crystallization kinetics indicated by the appearance
of cold crystallization in the DSC (Figure S22). This may be
due to the random distribution of alcohol functional groups
result of selective degradation of isotactic sequences or preventing the crystallization of vinyl ether homopolymer
epimerization at the backbone methine (Figure S18). sequences or a potential reduction in isotacticity for poly(vinyl
To illustrate the opportunities afforded by the increased ether) homopolymer sequences (75% m, Figure S107). These
substrate scope in this method, we sought to further explore results point to tunable composition and properties being
the use of 2-nitrobenzyl vinyl ether as a vinyl alcohol synthon. achievable through this synthetic method.
We hypothesized that this monomer would enable the two-
step synthesis of an isotactic poly(vinyl ether-co-vinyl alcohol)
copolymer, which would combine the desirable polarity of
■ CONCLUSION
In conclusion, data science techniques have been used to
alcohol functional groups with the semicrystallinity of isotactic provide unique insight into the factors that affect selectivity in
poly(vinyl ether) segments (Figure 7A). Stereoselective stereoselective cationic polymerization. Over 40 experimental
polymerization using catalyst 1c with an initial monomer data points contributed to a robust MVLR model with three
stoichiometry of 80:20 benzyl vinyl ether:2-nitrobenzyl vinyl parameters that predicted selectivity. The model indicated that
ether resulted in a copolymer with 17% 2-nitrobenzyl repeat the dihedral angle of the BINOL catalyst scaffold, the sterics
units and a tacticity of 86% m. This copolymer was subjected (Bmin) of the BINOL aryl substituent, and the polarizability of
to irradiation with a broadband UV light source for 20 min the monomer contributed to the selectivity of the system.
(see Supporting Information for details), after which 1H NMR Based on analysis of MVLR parameters and computed
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structures of the IDPi/chain-end ion pair, we hypothesized

that lower confinement catalysts gave higher selectivity due to
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■ ASSOCIATED CONTENT
* Supporting Information
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■ AUTHOR INFORMATION
Corresponding Author
(9) Wu, Y.; Liu, X.; Zhang, C.; Zhang, X.; Lin, X. Bulk
Stereoselective Cationic Polymerization of Vinyl Ethers by the
Coordination of ZrCl 4 with Tunable Spirocyclic Phosphoric Acids.
Angew. Chem., Int. Ed. 2025, 64, No. e202422085.
Frank A. Leibfarth − Department of Chemistry, University of (10) Watanabe, H.; Yamamoto, T.; Kanazawa, A.; Aoshima, S.
North Carolina Chapel Hill, Chapel Hill, North Carolina Stereoselective Cationic Polymerization of Vinyl Ethers by Easily and
27599, United States; [Link]/0000-0001-7737-0331; Finely Tunable Titanium Complexes Prepared from Tartrate-Derived
Email: frankl@[Link] Diols: Isospecific Polymerization and Recognition of Chiral Side
Chains. Polym. Chem. 2020, 11 (20), 3398−3403.
Authors (11) Oishi, M.; Yamamoto, H. Polymerization of t -Butyl Vinyl
Caleb T. Kozuszek − Department of Chemistry, University of Ether Mediated by an Aluminum Lewis Acid−TrF System and Its
North Carolina Chapel Hill, Chapel Hill, North Carolina Complex Structure−Tacticity Correlation. Bull. Chem. Soc. Jpn. 2001,
27599, United States 74 (8), 1445−1454.
Cole C. Sorensen − Department of Chemistry, University of (12) Yang, Z.; Liao, Y.; Zhang, Z.; Chen, J.; Zhang, X.; Liao, S.
North Carolina Chapel Hill, Chapel Hill, North Carolina Asymmetric Ion-Pairing Photoredox Catalysis for Stereoselective
27599, United States; Department of Chemistry, Princeton Cationic Polymerization under Light Control. J. Am. Chem. Soc. 2024,
146 (10), 6449−6455.
University, Princeton, New Jersey 08544, United States; (13) Singha, S.; Pan, S.; Tallury, S. S.; Nguyen, G.; Tripathy, R.; De,
[Link]/0000-0002-0705-9406 P. Recent Developments on Cationic Polymerization of Vinyl Ethers.
Complete contact information is available at: ACS Polym. Au 2024, 4 (3), 189−207.
[Link] (14) Uchiyama, M.; Satoh, K.; Kamigaito, M. Cationic RAFT
Polymerization Using Ppm Concentrations of Organic Acid. Angew.
Chem., Int. Ed. 2015, 54 (6), 1924−1928.
Funding
(15) Ouchi, M.; Sueoka, M.; Kamigaito, M.; Sawamoto, M.
This work was supported by the National Institute of General Stereoregulation in Cationic Polymerization. III. High Isospecificity
Medical Sciences of the National Institute of Health under with the Bulky Phosphoric Acid [(RO)2PO2H]/SnCl4 Initiating
Award Number 1-R35-GM142666−01. The UNC Department Systems: Design of Counteranions via Initiators. J. Polym. Sci., Part A:
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instrumentation that enabled this study, with support from the (16) Uchiyama, M.; Watanabe, D.; Tanaka, Y.; Satoh, K.; Kamigaito,
National Science Foundation (CHE-1828183 and CHE- M. Asymmetric Cationic Polymerization of Benzofuran through a
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The authors declare no competing financial interest. (17) Aoshima, S.; Iwasa, S.; Kobayashi, E. Living Cationic
Polymerization of Benzyl Vinyl Ether and Its Block Copolymers
■ ACKNOWLEDGMENTS
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