Bidirectional Suzuki Catalyst Transfer Polymerization of Poly(p‑phenylene)

Abstract

Suzuki catalyst transfer polymerization (SCTP) has emerged as an effective method for accessing length-controlled π-conjugated poly­(p-phenylene). Regio-controlled functional group sequencing along the backbone and the chain ends of synthetic polymers remains a challenge for the successful integration of organic semiconductors in sensors and electronic devices. Here, we report a bidirectional SCTP system based on dinuclear palladium­(II) initiators. Functional groups transferred during the initiation and termination steps unlock independently addressable synthetic handles at the polymer core and respective chain ends. These functional groups open opportunities for late-stage regio-controlled and chemoselective derivatizations. Control over key polymer parameters, including molecular weight (M _n), dispersity (Đ = M _w/M _n), degree of polymerization (DP), termination efficiency, and functional group interconversion, is corroborated by size exclusion chromatography (SEC) and NMR spectroscopy. The modular design of SCTP initiators, in combination with commercially available terminating groups, represents a highly flexible toolbox for late-stage polymer conjugation, e.g., chemoselective anchoring groups for integration with functional electronics or bioorthogonal conjugation for molecular sensing.

Introduction

Transition metal-catalyzed polycondensation reactions are ubiquitous in carbon–carbon bond formation. Over decades, these reactions have served as robust workhorses that have been adapted and optimized to develop a myriad of π-conjugated molecular systems with well-defined structures. − Among these, poly­(p-phenylene) has been synthesized almost exclusively through step-growth polymerization mechanisms that suffer from unpredictable molecular weight distributions resulting in large polymer dispersities. Prompted by this challenge, recent efforts have embraced Suzuki catalyst transfer polymerization (SCTP, Scheme , top) as an efficient technique for exercising control over critical polymer structure parameters, − e.g., number-average molecular weight (M _n) and dispersity (Đ = M _w/M _n; M _w is the weight-average molecular weight) of poly­(p-phenylene) systems used as precursors in graphene nanoribbon (GNR) synthesis. − Effectively employing discrete Pd­(II) complexes as SCTP initiators, these formative works have contributed important tools for growing π-conjugated polymers with distinct topologies that combine solution synthesis and advanced electronic circuit fabrication. Despite this progress, achieving regio-controlled functional group sequencing has persisted as a grand challenge hindering the transformation of conjugated poly­(p-phenylene) into electronically compatible nanomaterials. Seamless integration of poly­(p-phenylene) into functional materials not only demands intentional control over polymer lengths but requires dependable strategies to discretely pattern their conjugated backbones with independently addressable functional handles. − Harnessing the uncompromising control over these key parameters is requisite to overcoming fundamental chemical, biological, physical, and engineering challenges that hold the key to multiplexed on-chip sensing technologies.

1. Suzuki Catalyst Transfer Polymerization.

We herein demonstrate a succinct yet highly modular length-controlled polymerization that builds on bidirectional, isoregic CTP mechanisms and gives facile access to telechelic polymers. − Our strategy is based on an asymmetric o-terphenylene monomer (M) that features a pair of orthogonal cross-coupling functional groups  an arylboronate ester (BPin) and an arylhalide (Br) group  on either side of a central phenyl ring defining the axis of polymerization (Scheme , bottom). One-dimensional (1D) polymer chains form under the action of a discrete preformed bidirectional SCTP initiator (I). Throughout the propagation stage the active catalyst-ligand systems remain coordinated to the π-system of the polymer chain-ends as they migrate to the terminal C–Br groups. Intramolecular oxidative addition primes the catalysts for subsequent intermolecular transmetalation with the arylboronate groups of the approaching monomers. Irreversible condensation reactions with monofunctional terminators (T), followed by chemoselective postpolymerization functionalization, offer an elegant pathway to diverse, regio-controlled polymer derivatives. Both the SCTP initiators, as well as the terminating groups, can be readily adapted to template a wide variety of unique derivatizations. The ability to leverage chemoselective and site-specific poly­(p-phenylene) functionalization through judicious catalyst design could broaden the scope of bioconjugation reactions: e.g., anchoring groups, required for directed self-assembly between metal contacts − can be placed at either end of the polymer chain, or bioorthogonal functional handles can be selectively installed on the core of the polymers through subsequent conjugation reactions with complementary biorecognition domains. − This modular SCTP system serves as a proof-of-concept platform for scalable carbon-based nanomaterials that venture to narrow the gap between the single molecule scale and traditional macroscopic electrical circuit elements.

Results and Discussion

Design and Synthesis of Bidirectional SCTP Catalyst

Our strategy to access bidirectional SCTP catalysts is derived from an aryl-halide Pd­(II)-complex recently reported as a competent initiator in the living polymerization of o-terphenylenes. The synthesis of the Pd-complexes 1a and 1b used as SCTP initiators throughout this study is depicted in Figure . Regioselective Suzuki–Miyaura cross coupling of 1,4-dibromo-2,5-diiodobenzene (3) with 4-formylphenylboronic acid gives the p-terphenyl 4a. Protection of the terminal aldehydes in 4a as dioxolanes (4b) not only introduces pendant solubilizing groups (C₈H₁₇) at the core of the initiator that greatly simplify isolation and purification but masks a versatile handle for chemoselective and regio-controlled functionalization at the polymer stage highlighted below. Irrespective of the substitution, both dibromo-p-terphenyls 4a,b undergo oxidative addition with bis­[(trimethylsilyl)­methyl]­(1,5-cyclooctadiene)­palladium­(II) in the presence of RuPhos to afford the Pd­(RuPhos) aryl dibromide catalysts 1a and 1b, respectively. Single crystals suitable for X-ray diffraction were obtained by slow diffusion of pentane into a saturated solution of 1a in CHCl₃. In the crystal, 1a adopts quasi-C _i symmetric conformation. The Pd-atoms are coordinated in a square planar geometry to the central ring of the p-terphenyl, the bromine, and the P atom lone-pair of the RuPhos ligand. The fourth coordination site is occupied by an interaction with the ipso 1’ C atom of the RuPhos ligand (Pd–C_ipso = 2.455 Å). Here, the Pd–C_ipso interactions stabilize the oxidative addition complex prior to transmetalation. ,

1.

Synthesis of bidirectional SCTP initiators 1a,b. Single X-ray crystal structure of 1a is shown. Thermal ellipsoids are drawn at the 50% probability level. Color coding: C (gray), O (red), P (purple), Br (orange), and Pd (teal). Hydrogen atoms are omitted for clarity.

Bidirectional Suzuki Catalyst Transfer Polymerization

Solubilized o-terphenylene monomer 2 (R² = C₁₂H₂₅) polymerizes readily under the action of either of the bidirectional initiators 1a,b, in the presence of an aqueous base (K₃PO₄) and RuPhos (0.24 equiv) in tetrahydrofuran (THF) at 24 °C, to give the characteristic p-phenylene backbone (Scheme ). Termination of the intermediate propagating chain ends with an excess of phenyl boronic acid 5 or 6 yields the corresponding polymers, poly-2a, poly-2b, and poly-2c, featuring methyl ester or aldehyde functional groups at either end of the chain.

2. Controlled Bidirectional Suzuki Catalyst Transfer Polymerization.

Size exclusion chromatography (SEC) calibrated to polystyrene (PS) standards reveals monomodal distributions of poly-2 resulting from bidirectional SCTP across a wide range of [M]₀/[I]₀ loadings (Figure A). The number-average molecular weights (M _n), Đ, degrees of polymerization (DP), average polymer lengths (l̅), termination efficiencies, and isolated polymer yields are summarized in Table . SEC of polymer samples initiated by 1a show a linear correlation between M _n and initial loading [M]₀/[I]₀ ranging from M _n = 14.1 kDa to 24.5 kDa (Figure B). SEC reveals negligible changes to polymer dispersities (1.46 ≤ Đ ≤ 1.68) as [M]₀/[I]₀ increases from 20 to 100. Samples of poly-2 initiated with 1a taken at different time points from an SCTP reaction mixture ([M]₀/[I]₀ = 25) show a linear correlation between monomer conversion and M _n indicative of a living chain-growth mechanism (Figure S1). MALDI-TOF mass spectrometry of poly-2c shows a characteristic family of peaks separated by the monomer repeat unit (Figure C). The mass of the detected molecular ions [M]⁺ = [poly-2c]⁺ corresponds to bidirectional polymers functionalized on either end by benzaldehyde groups and spans from 9 < DP < 25 for [M]₀/[I]₀ = 20. The fragmentation observed under the forceful conditions required to ionize poly-2c gives rise to a second family of peaks corresponding to [M]⁺ = [poly-2c – (C₆H₄CHO)₂ – (CHO)₂]⁺ marked by an asterisk in Figure C. The fragmentation pattern and structural assignments were further corroborated using Kendrick Mass Defect (KMD) analysis (Figure S2). ¹H NMR analyses of poly-2a,b samples provides clear evidence for the formation of telechelic polymers. The characteristic resonances corresponding to the aldehyde (δ = 9.98, 2H) in poly-2a or the dioxolane (δ = 4.19–4.04 ppm, 4H and 3.73–3.49 ppm, 2H) groups in poly-2b introduced by the core of the respective initiators, 1a and 1b, appear as slightly broadened signatures in Figure D. When integrated against the benzylic methylene groups associated with the o-terphenylene monomer 2 (δ = 2.44 ppm), these core resonances provide an independent estimate for the average DP. Figure S3 shows a linear correlation between [M]₀/[I]₀ loading, and DP expected for a living chain-growth mechanism. Termination efficiencies of SCTP reactions can be extrapolated by integration of the characteristic resonances corresponding to the esters arising from termination with 5 (δ = 3.84 ppm, 6H), or the aldehydes introduced by termination with 6 (δ = 9.88 ppm, 2H). Careful integration against resonances attributed to the functional groups on the respective SCTP initiators suggests termination efficiencies exceeding 90% for [M]₀/[I]₀ loadings ranging from 20 to 40. Deprotection of the dioxolanes at the core of poly-2b to the respective aldehydes gives rise to poly-2c. ¹H NMR spectra show a broad resonance (δ = 9.98 ppm, 2H) next to the sharp singlet (δ = 9.88 ppm, 2H) associated with the terminal aldehyde groups (Figure D). Both resonances reliably integrate to a 1:1 ratio across wide [M]₀/[I]₀ loadings, further supporting the reliable termination of the bidirectional SCTP at both chain ends.

2.

Controlled bidirectional Suzuki catalyst transfer polymerization. (A) SEC traces of poly-2c obtained from various [M]₀/[I]₀ loadings. (B) Linear correlation between M _n and [M]₀/[I]₀. Đ remains stable for different [M]₀/[I]₀ loadings. (C) MALDI of poly-2c ([M]₀/[I]₀ = 20) showing a primary family of polymers separated by the mass of the monomer unit. The main family of molecular ion peaks correspond to the mass of the polymer [M]⁺ = [poly-2c]⁺. A second family of peaks highlighted by asterisks corresponds to a fragmentation pattern [[M]⁺ = [poly-2c – (C₆H₄CHO)₂ – (CHO)₂]⁺. (D) ¹H NMR spectra showing the regio-controlled site-specific functionalization of poly-2a–f (spectra are offset by I/I _max = 0.4; dashed lines indicate the transformation of aldehydes to imines).

1. Summary of SEC Data, Estimated Length, Termination Efficiency and Isolated Yield of Polymers as a Function of [M]₀/[I]₀ Loading.

entry	polymer	[M]0/[I]0	Mn (kDa)	Đ	DP	length (nm)	termination (%)	yield (%)
1	poly-2a	20	10.5	1.51	25	10.8	95	76
2	poly-2a	40	14.6	1.45	40	17.2	99	98
3	poly-2b	20	12.1	1.46	24	10.3	95	61
4	poly-2b	40	14.6	1.63	41	17.6	95	92
5	poly-2c	20	14.1	1.56	24	10.3	98	72
6	poly-2c	40	16.5	1.49	44	18.9	97	67
7	poly-2c	60	18.8	1.57	64	27.5	98	65
8	poly-2c	80	20.7	1.68	80	34.4	97	81
9	poly-2c	100	24.5	1.68	103	44.3	95	70

^aCalibrated to PS standards.

^bDetermined by SEC.

^cDetermined by ¹H NMR.

^dAverage length based on DP.

^eIsolated yield.

Regio-Controlled Functionalization of SCT Polymers

We next sought to explore the regio-controlled site-specific functionalization of poly-2a–c. Scheme shows poly-2a,b undergo reversible condensation with N ¹,N ¹-dimethylbenzene-1,4-diamine (DMPPDA) to give the Schiff-bases at either the core of the p-terphenyl initiator (poly-2d) or the terminating end-groups (poly-2e), respectively. The control imparted by our chemoselective platform is supported by ¹H NMR analysis. Figure D shows how a broad resonance assigned to the H atom of the internal aldehyde group in poly-2a is upfield shifted (Δδ = 1.50 ppm, 2H) in the imine group of the corresponding Schiff-bases in poly-2d. A similar shift (Δδ = 1.49 ppm, 2H) is observed for the interconversion of the terminal aldehyde groups in poly-2b to their respective imines in poly-2e. MALDI-TOF mass spectrometry of poly-2e shows a characteristic family of peaks separated by the monomer repeat unit (Figure S4). The mass of the detected molecular ions [M]⁺ = [poly-2e + Na] corresponds to bidirectional polymers functionalized on either end by the imine group and spans from 6 < DP < 20 for [M]₀/[I]₀ = 20. Analogous transformations with tetra-aldehyde poly-2c give rise to the tetra-imine functionalized polymer poly-2f. The success of the postpolymerization functionalization in poly-2a–c can be estimated by integration of the diagnostic peak associated with the Schiff-bases, the N,N-dimethylamine groups, against internal standards, e.g., the methyl ester, dioxolane, or coalesced benzylic methylene protons in the solubilizing dodecyl chains that remain unperturbed by this transformation. Postpolymerization functionalization yields generally exceed 90% for [M]₀/[I]₀ loadings assayed from 20 to 40 without any notable degradation of the polymer structure. Table S1 shows that M _n and Đ for poly-2d–f are consistent with SEC data determined for their respective poly-2a–c precursors.

3. Regioselective Functionalization of Poly-2a–c .

The regio-controlled late-stage functionalization of SCT polymers poly-2a–c is not restricted to reversible carbonyl-amine condensation reactions. The introduction of terminal alkyne groups, ubiquitously exploited in biorthogonal azide–alkyne [3 + 2] cycloaddition reactions, offer opportunities to selectively interface synthetic polymers with biomolecules. Scheme shows a Seyferth-Gilbert homologation of unprotected aldehydes at the polymer core and chain ends that site-selectively introduces primary alkyne groups. Reaction of poly-2a,b with Bestmann-Ohira reagent maps pairs of terminal alkynes onto the initiator core (poly- 2g) or the terminating end groups (poly- 2h), respectively. Figure S5 shows the emergence of a broadened ¹H NMR resonance at δ = 3.08 ppm (2H) associated with the terminal alkynes linked to the p-terphenylene core (poly- 2g). A sharper resonance (δ = 2.99 ppm, 2H) in poly- 2h supports the introduction of terminal alkynes at the polymer chain ends. Analogously, conversion of poly-2c gives rise to the tetra-alkyne functionalized polymer poly-2i. Homologation conversions generally exceed 90% for [M]₀/[I]₀ = 40 without any notable degradation of the polymer structure. Table S1 shows that M _n and Đ for poly-2g–i are consistent with SEC data determined for their respective poly-2a–c precursors. Integration of the alkyne signals against internal standards reveals similar conversion rates (>90%), as observed for the Schiff-base condensations, and further validates bidirectional SCTP as a highly modular toolbox for regio-controlled, chemoselective late-stage polymer-functionalization.

Conclusions

We herein demonstrate the design and performance of bidirectional SCTP catalysts based on dinuclear palladium­(II) complexes that give rise to telechelic poly­(p-phenylene). SEC and NMR spectroscopy independently corroborate the exquisite control over key polymer parameters, including molecular weight, dispersity, degree of polymerization, and termination efficiency. The resulting polymers feature independently addressable chemical handles lining the core and both chain ends transferred during the initiating and terminating steps. Efficient regio-controlled and chemoselective postpolymerization homologation of these aldehyde groups opens a path for the functional integration of metal selective anchoring groups at either end of a π-conjugated molecular wire or offers access to site-selective terminal alkynes as functional handles in bioorthogonal conjugation.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.macromol.5c00851.

• Evolution of M _n as a function of monomer 2 conversion; Kendrick polymer analysis of poly-2c ([M]₀/[I]₀ = 20); linear correlation between DP determined by ¹H NMR analysis and [M]₀/[I]₀; MALDI of poly-2e ([M]₀/[I]₀ = 20); ¹H and ¹³C­{¹H} NMR spectra; single X–ray crystal structure of 1a (Figures S1–S37); synthesis of compounds (Schemes S1–S6); summary of SEC data, estimated length, percent conversions, and isolated yields of poly-2d–i; crystal data and structure refinement for 1a (Tables S1–S7); experimental details; materials and methods (PDF)

CCDC 2323736 contains the supplementary crystallographic data for 1a. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

The authors declare no competing financial interest.