- Email: [email protected]
Placing Functionality Where You Want: The Allure of Sequence Control
(2014). Mechanistic insights into the interfacedirected transformation of thiols into disulfides and molecular hydrogen by visiblelight irradiation of quantum dots. Angew. Chem. Int. Ed. Engl. 53, 2085–2089. 5. Liu, H., Xu, C., Li, D., and Jiang, H.-L. (2018). Photocatalytic hydrogen production coupled with selective benzylamine oxidation over MOF composites. Angew. Chem. Int. Ed. Engl. 57, 5379– 5383. 6. Zheng, Y.-W., Chen, B., Ye, P., Feng, K., Wang, W., Meng, Q.-Y., Wu, L.-Z., and Tung, C.-H. (2016). Photocatalytic hydrogen-
evolution cross-couplings: benzene C-H amination and hydroxylation. J. Am. Chem. Soc. 138, 10080–10083. 7. Guo, Q., Liang, F., Li, X.-B., Gao, Y.-J., Huang, Wang, Y., Xia, S.-G., Gao, X.-Y., Gan, Q.-C., Lin, Z.-S., et al. (2019). Efficient and selective CO2 reduction integrated with organic synthesis by solar energy. Chem 5, this issue, 2605–2616. 8. Ghuman, K.K., Hoch, L.B., Szymanski, P., Loh, J.Y.Y., Kherani, N.P., El-Sayed, M.A., Ozin, G.A., and Singh, C.V. (2016). Photoexcited surface frustrated lewis pairs for
heterogeneous photocatalytic CO2 reduction. J. Am. Chem. Soc. 138, 1206–1214. 9. Nakajima, M., Fava, E., Loescher, S., Jiang, Z., and Rueping, M. (2015). Photoredoxcatalyzed reductive coupling of aldehydes, ketones, and imines with visible light. Angew. Chem. Int. Ed. Engl. 54, 8828–8832. 10. Zhong, J.-J., To, W.-P., Liu, Y., Lu, W., and Che, C.-M. (2019). Efficient acceptorless photo-dehydrogenation of alcohols and N-heterocycles with binuclear platinum(ii) diphosphite complexes. Chem. Sci. (Camb.) 10, 4883–4889.
Preview
Placing Functionality Where You Want: The Allure of Sequence Control Zhishuai Geng,1 Jongbok Lee,1 and Craig J. Hawker1,* In this issue of Chem, Xia and coworkers employ user-friendly ring-opening metathesis polymerization (ROMP) and cyclopropene monomers (CPEs) to achieve multiple single additions of CPEs along a polymer backbone. This simple yet powerful strategy greatly expands the scope of sequence-controlled materials and allows key questions to be addressed. The synthesis of sequence-controlled and sequence-defined macromolecules is an emerging challenge in polymer science. Driven by the desire to have a degree of structural control that is traditionally found only with proteins and other biological systems, the promise of sequence-controlled macromolecules has drawn considerable attention.1 Coupled with the structural control over the position of multiple repeat units along a polymer chain is the potential for accessing unique properties and applications, again typically only found in biomaterials. As a result, the development of procedures for preparing sequence-controlled and sequence-defined macromolecules from readily available monomers would enable new directions in fields ranging from polymer physics to mate-
rials science and nanotechnology.2 During the last decade, significant effort has focused attention on key issues such as the importance of precise sequence control versus sequence dispersity, scalability of user-friendly procedures, and the overarching question for this emerging field—what benefits and new properties emerge from sequence control in synthetic systems.3 To illustrate recent synthetic advances toward scalable, sequence-defined materials, several approaches involving termination with a specific, non-propagating monomer and then transformation of this chain end back to an active, propagating unit have been examined. For example, allyl alcohol was used as a chain-end capping agent during
2510 Chem 5, 2508–2519, October 10, 2019 ª 2019 Elsevier Inc.
atom-transfer radical polymerization (ATRP), followed by oxidation and esterification to ‘‘reactivate’’ the chain end.4 In a similar fashion, an additioncleavage-regeneration cycle can be realized through dynamic bonds by connecting a radical-generating site with an alkene chain end as described by Sawamoto and coworkers.5 While successful for controlling a limited number of monomer insertions, multiple purification steps are necessary, decreasing the applicability of these strategies for high-molecular-weight polymers and true single-monomer insertions. Increased sequence regulation with near-single-monomer precision can be attained using specific comonomer pairs that copolymerize in an alternating manner. In these systems, cross-propagation is favored over homo-propagation with electron-rich monomers (e.g., styrene or indene) and electron-poor monomers (e.g., maleimide) copolymerizing to give an AB-repeating sequence. By exploiting living polymerizations and multiple monomer additions, Lutz and coworkers have shown that controlled
1Materials
Research Laboratory, University of California, Santa Barbara, Santa Barbara, CA 93106, USA *Correspondence: [email protected] https://doi.org/10.1016/j.chempr.2019.09.007
Figure 1. Schematic Illustration of Precise Placement of Individual CPE Units at Pre-determined Locations along a Multiblock Copolymer Backbone Post-polymerization modifications were demonstrated from functionalized CPE units.
introduction of functional units along a polymer chain6 can be achieved by the controlled radical polymerization of styrene with stoichiometric amounts of maleimide comonomers being added at specific times. The alternating nature of the copolymerization then leads to control over the position of the electron-poor monomer units in the polymer backbone. The widespread availability of vinyl monomers and synthetic ease achieved with controlled radical processes illustrate the potential for scalable synthesis; however, precision is limited, as non-ideal reactivity ratios inevitably lead to chain-chain deviations in length, composition, and monomer sequence. In an effort to further drive the field to precise sequence control, the Xia group has examined cylcopropenes
(CPEs) as a privileged class of sequence-controlled monomers.7–9 While highly strained, CPE-based monomers are synthetically accessible, are stable at ambient conditions, and have a strong thermodynamic driving force for ring-opening metathesis polymerization (ROMP). Additionally, CPEs can be readily modified to introduce various functional groups either directly or through post-modification. In preliminary studies, Xia and coworkers observed that symmetrical, disubstituted CPEs undergo only a single monomer insertion in the presence of Grubbs III catalyst (G3) rather than homopolymerization.7 The resulting sterically hindered Ru complex prevents addition of a second CPE unit. However, in a seminal demonstration, reactivity was retained with other ROMP monomers, leading to true alternation. This exciting discovery has been
further expanded to the selective chainend functionalization via addition of a single CPE unit.9 In this issue of Chem, Xia and coworkers have significantly expanded this structural control to precisely locate functional CPE units at desired positions along a living polymer chain (Figure 1).10 The rapid and userfriendly nature of ROMP allows individual CPE units to be specifically placed at pre-determined locations along the backbone of a range of polynorbornene polymers. This strategy is facilitated by the development of procedures for the quantitative re-initiation of the Ru complex after reaction with functional CPE units. By addition of a labile ligand (3-bromopyridine) and/or lowering the reaction temperature, this straightforward method could be applied to the single addition of
Chem 5, 2508–2519, October 10, 2019 2511
functional CPE monomers containing an ATRP initiator, Boc-protected amine, or NHS ester, affording controlled molecular weight and narrow dispersity materials without intermediate purification. The exclusive insertion of single CPE units at multiple positions along the backbone was realized by adjusting the stoichiometric amount of norbornene and through multiple additions of CPE and norbornene repeat units during the ROMP process. Precise placement of chromophores (perylene and pyrene functionalized CPEs) at arbitrary pre-determined locations along the polymer chain also allowed Xia and coworkers to investigate the effect of sequence control on fluorescence resonance energy transfer (FRET). The high degree of structural control in these systems clearly illustrated that energy transfer was highly distance and sequence dependent. Moreover, post-polymerization modification of these functional side chains was successfully demonstrated, leading to polynorbornenes with singly incorporated functionalized CPEs that could be used as a macroinitiator or macromonomer. This rigorous control over branching points enabled the precise tailoring of complex architectures, such as star polymers, by ‘‘grafting
2512 Chem 5, 2508–2519, October 10, 2019
from,’’ ‘‘chain linking,’’ and ‘‘grafting through’’ strategies. Of perhaps greatest impact to the field of sequence-control polymers is the demonstration that multiple single additions of CPEs at different positions along a polynorbornene multiblock copolymer backbone could be achieved during a one-pot ROMP process. This simple yet powerful strategy greatly expands the scope of sequence-controlled materials with various architectures and functional building blocks now obtainable in multi-gram quantities. It is anticipated that the versatility of this approach will facilitate the discovery of unique properties and applications based on sequence-controlled macromolecules, addressing key questions in the field and permitting the next generation of polymer materials to be imagined.
ACKNOWLEDGMENTS The research reported here was primarily supported by the National Science Foundation (NSF) Materials Research and Engineering Center at UC Santa Barbara, DMR-1720256 (IRG-3). 1. Xu, J., Fu, C., Shanmugam, S., Hawker, C.J., Moad, G., and Boyer, C. (2017). Synthesis of discrete oligomers by
sequential PET-RAFT single-unit monomer insertion. Angew. Chem. Int. Ed. Engl. 56, 8376–8383. 2. Lutz, J.-F., Ouchi, M., Liu, D.R., and Sawamoto, M. (2013). Sequence-controlled polymers. Science 341, 1238149. 3. Gody, G., Zetterlund, P.B., Perrier, S., and Harrisson, S. (2016). The limits of precision monomer placement in chain growth polymerization. Nat. Commun. 7, 10514. 4. Tong, X., Guo, B.H., and Huang, Y. (2011). Toward the synthesis of sequence-controlled vinyl copolymers. Chem. Commun. (Camb.) 47, 1455–1457. 5. Hibi, Y., Ouchi, M., and Sawamoto, M. (2016). A strategy for sequence control in vinyl polymers via iterative controlled radical cyclization. Nat. Commun. 7, 11064. 6. Pfeifer, S., and Lutz, J.-F. (2007). A facile procedure for controlling monomer sequence distribution in radical chain polymerizations. J. Am. Chem. Soc. 129, 9542–9543. 7. Elling, B.R., and Xia, Y. (2015). Living alternating ring-opening metathesis polymerization based on single monomer additions. J. Am. Chem. Soc. 137, 9922– 9926. 8. Elling, B.R., Su, J.K., and Xia, Y. (2016). Ring-opening metathesis polymerization of 1,2-disubstituted cyclopropenes. Chem. Commun. (Camb.) 52, 9097–9100. 9. Elling, B.R., and Xia, Y. (2018). Efficient and facile end group control of living ringopening metathesis polymers via single addition of functional cyclopropenes. ACS Macro Lett. 7, 656–661. 10. Elling, B.R., Su, J.K., Feist, J.D., and Xia, Y. (2019). Precise placement of single monomer units in living ring-opening metathesis polymerization. Chem 5, this issue, 2691– 2701.
evolution cross-couplings: benzene C-H amination and hydroxylation. J. Am. Chem. Soc. 138, 10080–10083. 7. Guo, Q., Liang, F., Li, X.-B., Gao, Y.-J., Huang, Wang, Y., Xia, S.-G., Gao, X.-Y., Gan, Q.-C., Lin, Z.-S., et al. (2019). Efficient and selective CO2 reduction integrated with organic synthesis by solar energy. Chem 5, this issue, 2605–2616. 8. Ghuman, K.K., Hoch, L.B., Szymanski, P., Loh, J.Y.Y., Kherani, N.P., El-Sayed, M.A., Ozin, G.A., and Singh, C.V. (2016). Photoexcited surface frustrated lewis pairs for
heterogeneous photocatalytic CO2 reduction. J. Am. Chem. Soc. 138, 1206–1214. 9. Nakajima, M., Fava, E., Loescher, S., Jiang, Z., and Rueping, M. (2015). Photoredoxcatalyzed reductive coupling of aldehydes, ketones, and imines with visible light. Angew. Chem. Int. Ed. Engl. 54, 8828–8832. 10. Zhong, J.-J., To, W.-P., Liu, Y., Lu, W., and Che, C.-M. (2019). Efficient acceptorless photo-dehydrogenation of alcohols and N-heterocycles with binuclear platinum(ii) diphosphite complexes. Chem. Sci. (Camb.) 10, 4883–4889.
Preview
Placing Functionality Where You Want: The Allure of Sequence Control Zhishuai Geng,1 Jongbok Lee,1 and Craig J. Hawker1,* In this issue of Chem, Xia and coworkers employ user-friendly ring-opening metathesis polymerization (ROMP) and cyclopropene monomers (CPEs) to achieve multiple single additions of CPEs along a polymer backbone. This simple yet powerful strategy greatly expands the scope of sequence-controlled materials and allows key questions to be addressed. The synthesis of sequence-controlled and sequence-defined macromolecules is an emerging challenge in polymer science. Driven by the desire to have a degree of structural control that is traditionally found only with proteins and other biological systems, the promise of sequence-controlled macromolecules has drawn considerable attention.1 Coupled with the structural control over the position of multiple repeat units along a polymer chain is the potential for accessing unique properties and applications, again typically only found in biomaterials. As a result, the development of procedures for preparing sequence-controlled and sequence-defined macromolecules from readily available monomers would enable new directions in fields ranging from polymer physics to mate-
rials science and nanotechnology.2 During the last decade, significant effort has focused attention on key issues such as the importance of precise sequence control versus sequence dispersity, scalability of user-friendly procedures, and the overarching question for this emerging field—what benefits and new properties emerge from sequence control in synthetic systems.3 To illustrate recent synthetic advances toward scalable, sequence-defined materials, several approaches involving termination with a specific, non-propagating monomer and then transformation of this chain end back to an active, propagating unit have been examined. For example, allyl alcohol was used as a chain-end capping agent during
2510 Chem 5, 2508–2519, October 10, 2019 ª 2019 Elsevier Inc.
atom-transfer radical polymerization (ATRP), followed by oxidation and esterification to ‘‘reactivate’’ the chain end.4 In a similar fashion, an additioncleavage-regeneration cycle can be realized through dynamic bonds by connecting a radical-generating site with an alkene chain end as described by Sawamoto and coworkers.5 While successful for controlling a limited number of monomer insertions, multiple purification steps are necessary, decreasing the applicability of these strategies for high-molecular-weight polymers and true single-monomer insertions. Increased sequence regulation with near-single-monomer precision can be attained using specific comonomer pairs that copolymerize in an alternating manner. In these systems, cross-propagation is favored over homo-propagation with electron-rich monomers (e.g., styrene or indene) and electron-poor monomers (e.g., maleimide) copolymerizing to give an AB-repeating sequence. By exploiting living polymerizations and multiple monomer additions, Lutz and coworkers have shown that controlled
1Materials
Research Laboratory, University of California, Santa Barbara, Santa Barbara, CA 93106, USA *Correspondence: [email protected] https://doi.org/10.1016/j.chempr.2019.09.007
Figure 1. Schematic Illustration of Precise Placement of Individual CPE Units at Pre-determined Locations along a Multiblock Copolymer Backbone Post-polymerization modifications were demonstrated from functionalized CPE units.
introduction of functional units along a polymer chain6 can be achieved by the controlled radical polymerization of styrene with stoichiometric amounts of maleimide comonomers being added at specific times. The alternating nature of the copolymerization then leads to control over the position of the electron-poor monomer units in the polymer backbone. The widespread availability of vinyl monomers and synthetic ease achieved with controlled radical processes illustrate the potential for scalable synthesis; however, precision is limited, as non-ideal reactivity ratios inevitably lead to chain-chain deviations in length, composition, and monomer sequence. In an effort to further drive the field to precise sequence control, the Xia group has examined cylcopropenes
(CPEs) as a privileged class of sequence-controlled monomers.7–9 While highly strained, CPE-based monomers are synthetically accessible, are stable at ambient conditions, and have a strong thermodynamic driving force for ring-opening metathesis polymerization (ROMP). Additionally, CPEs can be readily modified to introduce various functional groups either directly or through post-modification. In preliminary studies, Xia and coworkers observed that symmetrical, disubstituted CPEs undergo only a single monomer insertion in the presence of Grubbs III catalyst (G3) rather than homopolymerization.7 The resulting sterically hindered Ru complex prevents addition of a second CPE unit. However, in a seminal demonstration, reactivity was retained with other ROMP monomers, leading to true alternation. This exciting discovery has been
further expanded to the selective chainend functionalization via addition of a single CPE unit.9 In this issue of Chem, Xia and coworkers have significantly expanded this structural control to precisely locate functional CPE units at desired positions along a living polymer chain (Figure 1).10 The rapid and userfriendly nature of ROMP allows individual CPE units to be specifically placed at pre-determined locations along the backbone of a range of polynorbornene polymers. This strategy is facilitated by the development of procedures for the quantitative re-initiation of the Ru complex after reaction with functional CPE units. By addition of a labile ligand (3-bromopyridine) and/or lowering the reaction temperature, this straightforward method could be applied to the single addition of
Chem 5, 2508–2519, October 10, 2019 2511
functional CPE monomers containing an ATRP initiator, Boc-protected amine, or NHS ester, affording controlled molecular weight and narrow dispersity materials without intermediate purification. The exclusive insertion of single CPE units at multiple positions along the backbone was realized by adjusting the stoichiometric amount of norbornene and through multiple additions of CPE and norbornene repeat units during the ROMP process. Precise placement of chromophores (perylene and pyrene functionalized CPEs) at arbitrary pre-determined locations along the polymer chain also allowed Xia and coworkers to investigate the effect of sequence control on fluorescence resonance energy transfer (FRET). The high degree of structural control in these systems clearly illustrated that energy transfer was highly distance and sequence dependent. Moreover, post-polymerization modification of these functional side chains was successfully demonstrated, leading to polynorbornenes with singly incorporated functionalized CPEs that could be used as a macroinitiator or macromonomer. This rigorous control over branching points enabled the precise tailoring of complex architectures, such as star polymers, by ‘‘grafting
2512 Chem 5, 2508–2519, October 10, 2019
from,’’ ‘‘chain linking,’’ and ‘‘grafting through’’ strategies. Of perhaps greatest impact to the field of sequence-control polymers is the demonstration that multiple single additions of CPEs at different positions along a polynorbornene multiblock copolymer backbone could be achieved during a one-pot ROMP process. This simple yet powerful strategy greatly expands the scope of sequence-controlled materials with various architectures and functional building blocks now obtainable in multi-gram quantities. It is anticipated that the versatility of this approach will facilitate the discovery of unique properties and applications based on sequence-controlled macromolecules, addressing key questions in the field and permitting the next generation of polymer materials to be imagined.
ACKNOWLEDGMENTS The research reported here was primarily supported by the National Science Foundation (NSF) Materials Research and Engineering Center at UC Santa Barbara, DMR-1720256 (IRG-3). 1. Xu, J., Fu, C., Shanmugam, S., Hawker, C.J., Moad, G., and Boyer, C. (2017). Synthesis of discrete oligomers by
sequential PET-RAFT single-unit monomer insertion. Angew. Chem. Int. Ed. Engl. 56, 8376–8383. 2. Lutz, J.-F., Ouchi, M., Liu, D.R., and Sawamoto, M. (2013). Sequence-controlled polymers. Science 341, 1238149. 3. Gody, G., Zetterlund, P.B., Perrier, S., and Harrisson, S. (2016). The limits of precision monomer placement in chain growth polymerization. Nat. Commun. 7, 10514. 4. Tong, X., Guo, B.H., and Huang, Y. (2011). Toward the synthesis of sequence-controlled vinyl copolymers. Chem. Commun. (Camb.) 47, 1455–1457. 5. Hibi, Y., Ouchi, M., and Sawamoto, M. (2016). A strategy for sequence control in vinyl polymers via iterative controlled radical cyclization. Nat. Commun. 7, 11064. 6. Pfeifer, S., and Lutz, J.-F. (2007). A facile procedure for controlling monomer sequence distribution in radical chain polymerizations. J. Am. Chem. Soc. 129, 9542–9543. 7. Elling, B.R., and Xia, Y. (2015). Living alternating ring-opening metathesis polymerization based on single monomer additions. J. Am. Chem. Soc. 137, 9922– 9926. 8. Elling, B.R., Su, J.K., and Xia, Y. (2016). Ring-opening metathesis polymerization of 1,2-disubstituted cyclopropenes. Chem. Commun. (Camb.) 52, 9097–9100. 9. Elling, B.R., and Xia, Y. (2018). Efficient and facile end group control of living ringopening metathesis polymers via single addition of functional cyclopropenes. ACS Macro Lett. 7, 656–661. 10. Elling, B.R., Su, J.K., Feist, J.D., and Xia, Y. (2019). Precise placement of single monomer units in living ring-opening metathesis polymerization. Chem 5, this issue, 2691– 2701.