Published in "Nature Chemistry 11(5): 488–494, 2019" which should be cited to refer to this work. Catalytic living ring-opening metathesis polymerization with Grubbs’ second- and third-generation catalysts Mohammad Yasir1,2, Peng Liu1,2, Iris K. Tennie1 and Andreas F. M. Kilbinger 1* In a conventional living ring-opening metathesis polymerization (ROMP), an equal number of ruthenium complexes to the num- ber of polymer chains synthesized are required. This can lead to high loadings of ruthenium complexes when aiming for shorter polymers. Here, a reversible chain-transfer agent was used to produce living ROMP polymers from norbornene derivatives using catalytic amounts of Grubbs’ ruthenium complexes. The polymers obtained by this method showed all of the character- istics of a living polymerization (that is, good molecular weight control, narrow molecular weight dispersities and the ability to form block copolymers). Monomers carrying functional moieties such as ferrocene, coumarin or a triisopropylsilyl-protected primary alcohol could also be catalytically polymerized in a living fashion. The method presented follows a degenerative chain- transfer process and is more economical and environmentally friendly compared with previous living ROMP procedures as it utilizes only catalytic amounts of costly and toxic ruthenium complexes. ing-opening metathesis polymerization (ROMP) is a polym- ruthenium contamination can make the synthesis of short polymer erization driven by the relief of the ring strain of cyclic olefins chains via a conventional living ROMP unattractive. R 1 to form polymers . Monomers such as norbornene derivatives Catalytic methods for the preparation of shorter ROMP can be polymerized in a living fashion due to the slow rates of irre- polymers have been reported. However, these methods rely versible chain-transfer events and termination reactions2 compared on irreversible chain-transfer agents (CTAs). The polymeriza- with the relatively fast propagation rates. Typical metathesis initia- tions are therefore non-living, showing broad molecular weight tors for ROMP are based on ruthenium3 or molybdenum4,5. The dispersities, meaning that the transfer agents cannot be used high tolerance of ruthenium complexes towards many polar func- to prepare block copolymers36,37. One way of achieving con- tional groups, water and oxygen has made them popular choices trol over molecular weights and molecular weight dispersities in organic as well as polymer chemistry6. The first and third gen- in polymerizations is degenerative chain transfer. Here, a CTA erations of Grubbs’ metathesis catalysts (G1 and G3, respectively; is used to reversibly terminate the chain growth of polymers. Fig. 1) are most commonly used for polymer synthesis due to This concept has been successfully employed in controlled radi- their high initiation-to-propagation-rate ratio7,8. Thus, ROMP has cal polymerizations (via the reversible addition–fragmentation emerged as one of the most popular polymerization techniques due chain-transfer (RAFT) process)38, degenerative chain growth of to its high functional group tolerance and the possibility of obtain- polyolefins39–41, ring-opening polymerizations of cyclic esters42 ing narrow dispersity polymers under mild reaction conditions and and cationic RAFT polymerization43. short reaction times. Recently, our group has reported a method based on a degenera- Functional ROMP polymers carrying ferrocenes9, chromo- tive reversible chain-transfer mechanism44 that used only catalytic phores10, fluorophores11 or reactive functional groups12–14 attached amounts of ruthenium complex (G3) for living ROMP. However, http://doc.rero.ch to the monomer units have been synthesized. ROMP polymers find we were not able to reproduce the data shown in that report and applications as electroactive15, mechanoresponsive16,17 or water- therefore retracted the article45. Nonetheless, the degenerative soluble polymers18. Recently, tandem ring-opening/ring-closing chain-transfer mechanism reported in the retracted paper could polymerizations of cycloalkenes attached to other cycloalkenes19 or be reproduced and confirmed, but the CTA (CTA1; Fig. 1) gives a terminal alkyne20–22 have been reported. Over the past decade, a much broader molecular weight dispersities and poorer molecular variety of methods for the preparation of mono and bis-end-func- weight control than was reported in the retracted paper. Here, we tional (telechelic) ROMP polymers have been developed23–27. ROMP report two different CTAs (CTA2 and CTA3; Fig. 1) that follow the polymers have also been prepared for biological/medicinal applica- originally proposed mechanism, and give kinetic evidence as to why tions28–30, electronics31–33, battery separators34, anion exchange mem- these work better than CTA1. branes35 and many others. Therefore, we report here a catalytic living ROMP with a revers- In a conventional living ROMP, the ruthenium carbene com- ible CTA (CTA2 or CTA3) that exploits a degenerative reversible plex represents the propagating species located at the end of every chain-transfer polymerization mechanism requiring only catalytic polymer chain. For this reason, equimolar amounts of ruthenium amounts of the ruthenium-based Grubbs’ second- (G2; Fig. 1) complex with respect to the polymer chains are required. This leads and third-generation (G3) metathesis catalysts, yielding poly- to rather high ruthenium complex loadings if short polymer chains mers with good molecular weight control and narrow molecular are aimed for. The associated increased costs and high levels of weight dispersities. 1Department of Chemistry, University of Fribourg, Fribourg, Switzerland. 2These authors contributed equally: Mohammad Yasir, Peng Liu. *e-mail: [email protected] 1 N N N N (Cy)3P Cl Cl Cl O Ru Ru N Ru Ph Ph Cl Ph Cl Cl R P(Cy)3 P(Cy)3 Br N Br G1 G2 G3 CTA0 CTA1 CTA2 R = phenyl (Ph) CTA3 R = cyclohexyl (Cy) O O X O O Si O O O O O N R2 N N Fe N O O 1 R O O O O 1 2 M1 R = H, R = CH3, X = CH2 M4 M5 M6 1 2 M2 R = CH2CH3, R = CH3, X = O 1 2 M3 R = H, R = (CH2)5CH3, X = CH2 Fig. 1 | Structure of the metathesis catalysts, CTAs and monomers investigated in this study. The metathesis catalysts include Grubbs’ first- (G1), second- (G2) and third-generation (G3) ruthenium carbene complexes. The CTAs include (E)-(2-cyclohexylvinyl) benzene (CTA0), (E)-(2-(cyclohex-2-en-1-yl)vinyl)benzene (CTA1), (E)-7-styryl-2,4a,5,6,7,7a-hexahydrocyclopenta[b]pyran (CTA2) and (E)-7-(2-cyclohexylvinyl)- 2,4a,5,6,7,7a-hexahydrocyclopenta[b]pyran (CTA3). The monomers include exo-N-methyl-norbornenecarboximide (M1), exo-4-ethyl-N-methyl-7- oxanorbornenecarboximide (M2), exo-N-hexyl-norbornenecarboximide (M3), exo-N-triisopropylsilyloxyethyl-norbornenecarboximide (M4), exo-N-ferrocenylcarbonyloxy-ethyl-norbornenecarboximide (M5) and exo-N-coumarin-3-carbonyloxy-ethyl-norbornenecarboximide (M6). M1 G3 Results and discussion solutions (20 equiv. and 1 equiv. in CD2Cl2; see Supplementary Our group recently published a report on functional metathesis Information) and added 10 equiv. of either CTA1 or CTA2. We then catalysts showing that a structural analogue of CTA2 reacted with followed the reactions with 1H NMR spectroscopy over time. CTA2 a propagating ruthenium carbene to transfer a cyclohexenyl end reacts rapidly with POLY-G3 (see Fig. 2a). The POLY-G3 ruthe- group onto the polymer chain ends while regenerating the ruthe- nium carbene signal (18.5 ppm) is completely shifted to a new signal nium benzylidene complex46. This prompted us to exploit CTA2 at 19.07 ppm (which corresponds to the G3-benzylidene complex) in catalytic living ROMP. We believed that CTA2, similar to its within 10 min. structural analogue, could be easily prepared from a functional In contrast, the identical reaction of CTA1 with POLY-G3 gener- norbornene derivative in a tandem ring-opening/ring-closing ated the G3-benzylidene 1H NMR signal only very slowly (Fig. 2b; reaction sequence. 47% conversion after 170 min). In separate 1H NMR experiments We observed that CTA2 reacted rapidly with G3-initiated (see the Supplementary Information), we estimated the kinetic propagating ROMP polymers to give end-functional polymers car- rate constants for the reaction of POLY-G3 with CTA1 (k = 0.001) rying the bicyclic fragment of CTA2 at the chain end. The exo- and CTA2 (k = 0.36). These data clearly confirm that CTA2 reacts cyclic double bond of CTA2 is sterically hindered, similar to the at least 300 times faster with the propagating polymer chain than main chain double bonds of poly(norbornene) derivatives. Due CTA1. We propose that this vast difference in rate constant could to the branching in both allylic positions, these double bonds do be due to an entropically favoured ring closure in CTA2, due to its not readily undergo secondary metathesis reactions. We therefore bicyclic conformational restriction. concluded that CTA2 reacted first with the propagating ruthenium Most likely, the POLY-G3 ruthenium carbene complex and CTA2 http://doc.rero.ch carbene via its endocyclic double bond in a ring-opening/ring- the endocyclic double bond of do not undergo a regioselec- closing sequence. tive ring-opening metathesis reaction and therefore give rise to two To prove the unreactive nature of the exocyclic double bond of ring-opened ruthenium alkylidene species (Fig. 3, centre). One CTA2, we synthesized the model compound CTA0 whose exocy- pathway (Fig. 3, centre top) yields a ring-opened carbene inter- clic double bond resembles that of CTA1 and CTA2 but lacks the mediate that cannot undergo a productive ring-closing metathesis endocyclic double bond. When CTA0 (10 equiv.) was added to a reaction (Fig. 3, centre top, red arrow) as this would form a highly G3-initiated exo-N-methyl-norbornenecarboximide (M1) solu- strained norbornene. This carbene intermediate will therefore tion (POLY-G3, prepared by adding 20 equiv. M1 to a solution of react back to the starting material and eventually undergo a G3 in CD2Cl2; see Supplementary Information), no reaction different ring-opening metathesis reaction yielding another inter- could be observed by 1H NMR spectroscopy after 10 min at room mediate carbene (Fig.