Aim of the department : protect the health of crops while respecting the environment, from the plant to the landscape.

✓ Explore a wide variety of questions, focusing on understanding the biology of deleterious and beneficial interactions between plants and associated organisms (pests, microbiota, pollinators, symbionts).

Contribute to the development of rational, efficient and durable protection against plant diseases

Ornamentals and plane tree

Virus

Bacteria Fungi

Fruits and vegetables produced in the Mediterranean basin

Plant Pathology Research Unit

General scientific objective :

Oilseed rape

Plant health research department

1.Etiology-diagnostics :

to identify emerging threats to crops

4.Plant protection :

to deploy this knowledge to conceive novel, environment-friendly and durable means for protecting plant health

3.Epidemiology of diseases :

to identify the main drivers of prevalence, diversity and spatial structure of plant pathogens

2.Ecology of pathogens :

to expand knowledge on the ecology and life history of plant pathogens

••

  equipment (mycology, bacteriology, virology laboratories) Technical skills from gene to landscape MISTRAL (MIcrobiology of agroeco-Systems : TRAnslational research from pathogen Life histories) Microbial biocontrol: an essential lever for reducing dependence on chemical pesticides against plant diseases [31 registered products in France, https://ephy.anses.fr/] Context • System in constant evolution : ✓Increasing complexity of farming practices ✓Global changes ➔ A situation that promotes variability in their efficacy and hinders their adoption • Diverse and often poorly understood modes of action [Köhl et al, 2018; Legein et al. 2020] • Protection tools based on natural regulations: more complex positioning than chemical pesticides. Success of protection depends on biotic and abiotic variables activation of the mode(s) of action ? Models to predict the activation of mechanisms of action according to main external environmental factors 1. Gain better understanding of complex interactions taking place at plant level Turc et al, 2023. CABI. Research interest: improve the field efficacy of biocontrol PIA-ADEME SCLEROZA, HORIZON-EU ADOPT-IPM, SPE-IMMIC Develop models to predict population fluctuations according to main external environmental factors Pathogen 2. Take into account the durability of protection efficacy 1. Demonstrated diversity in the susceptibily to biocontrol agents in populations of several plant pathogens 2. Demonstrated adaptation potential of certain pathogens to the action of biocontrol agents Risk for biocontrol protection to be overcome by plant pathogens ? Probability of resistance outbreak according to the mode(s) of action of the biocontrol agent and the targeted pathogen ? • Link between lack of consistency in field efficacy of biocontrol and the diversity in susceptibility within populations of the pathogen ? ANR CERES, CASDAR GARLIC, PIA-ADEME SCLEROZA, SPE-IMMIC Research interest: improve the field efficacy of biocontrol

Nitrogen fertilization

Plant pathogens Biocontrol agent

Plant resistance

• Efficacy of biocontrol modulated by other protection methods ?

• Genes (QTL) implicated in plant response to biocontrol agents ?

• Mechanisms implicated in plant defense induction (transcriptomic and metabolomic analyses)

• Is it possible to rely on indigenous plant microbiota ?


Miguel Palenzuela

Kamolchanok Sarisuta

Marta Navarro

Narumi Kumamoto

Nalinthip Chanthaset

Julien Monot

Hiroharu Ajiro

Blanca Martín-Vaca

Didier Bourissou

‡ Kamolchanok Sarisuta

Hiroaru Ajiro

5-Methylene-1,3-dioxane-2-one: A First-Choice Comonomer for Trimethylene Carbonate

come

Introduction

Aliphatic polycarbonates (APCs) are among the most investigated synthetic polymers for biomedical applications. i,ii,iii,iv,v Like polyesters, APCs possess the additional advantage of being in some cases accessible from natural and/or renewable sources. As a consequence, APCs are receiving growing attention as biodegradable and biocompatible materials not only for biomedical applications such as drug delivery or tissue engineering, but also for other applications (packaging, adhesives …). vi,vii,viii APCs are degraded in vivo mainly by enzymes, leading to a surface erosion that is rather slow. In marked contrast, aliphatic polyesters are degraded both enzymatically and hydrolytically via bulk erosion. ix,x Both families of polymers are thus complementary. An attractive advantage of APC over polyesters is that upon degradation, there is no release of acidic residues that may be hazardous to loaded drugs or living cells and tissues. ix,x APCs are typically prepared according to two different polymerization routes: (i) copolymerization of epoxides and CO2, xi,xii and (ii) ring-opening polymerization (ROP) of cyclic carbonates (CC), mainly six membered-ring cyclic carbonates, 6CCs. Although having the advantage of using CO2 as feedstock, the former strategy is a synthetic challenge as the used catalytic systems may suffer from low functional compatibility, and in many cases formation of the corresponding five membered-ring cyclic carbonate (5CC) is in competition with polymerization. Working at high CO2 pressure is often required for selective polymerization to take place. Nevertheless, important progresses have been achieved over the last decade in this regard, as well as in the utilization of bio-resourced epoxides. xi,xii The alternative strategy, ROP of 6CCs, has also received great attention not only with trimethylene carbonate (TMC), but also with a variety of substituted / functionalized 6CCs. xiii,xiv,xv,xvi Controlled ROP of these 6CCs under mild conditions has strongly benefited from the major progress done in organocatalytic ROP. A variety of organocatalysts are now available to promote the controlled polymerization of lactones and cyclic carbonates. In parallel, progress in the synthesis of substituted 6CCs, in particular regarding the cyclization step, has paved the way to a wide array of 6CCs featuring functional groups. i-v These functional groups enable to modulate mechanical properties, cell-tissue adhesion, hydrophilic-hydrophobic balance, degradation profile, etc. However, when the required functional group is protic, chemical compatibility issues appear either by quenching the organocatalyst or acting as initiator. This functional incompatibility imposes the utilization of protecting groups, which adds protection/deprotection steps to the synthetic process (Figure 1). To tackle this problem, post-polymerization modification by addition reactions (click) has emerged as a more atom-and step-economic approach. xvii In particular, pending vinyl groups have been introduced so that functionalization can be carried out after polymerization, typically by thiol-ene reaction, without resorting to protecting groups. xviii,xix,xx,xxi,xxii As for the microstructure of the functionalized APCs, the distribution of the functional groups along the copolymer chains is generally gradient-type. Indeed, substituted 6CCs and TMC usually display different reactivities in organocatalytic ROP and the balance between the two comonomers depends on the organocatalyst. Substituted 6CCs are more reactive than TMC when organocatalysts such as 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) or the association 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)/1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexyl-2-thiourea (TU) are used to promote the copolymerization. xxiii,xxiv On the contrary, they are less reactive when Brönsted acids such as methane sulfonic acid (MSA) are used. xxv As a consequence, simultaneous copolymerization leads to the formation of gradient copolymers, with a higher concentration of functional groups on one side of the polymer chain. The achievement of random copolymerization of functionalized 6CCs with TMC is therefore a challenge so that APCs featuring adjustable amounts of functional groups regularly distributed along the polymer chains can be prepared.

Aiming at developing a way to prepare functionalized polycarbonates of tuned structure (functional compatibility with the organocatalyst and random copolymerization with TMC), we became interested in 5-methylene-1,3-dioxane-2-one (exTMC), a 6CC featuring the reactive methylene group embedded in the ring skeleton as an exocyclic C=CH2 moiety. Besides opening the way for post-polymerization functionalization, it differs from the other comonomers in the presence of an sp 2 -hybridized carbon within the ring, which may induce a different polymerization profile. The ROP of exTMC was briefly investigated in the 1990's by T. Endo et al using strong Lewis or Brönsted acids as polymerization promotors, xxvi,xxvii but the polymerization exhibited low control and to the best of our knowledge, there has been no other report on exTMC (co)polymerization since then.

We report here that exTMC is in fact a comonomer of choice to access random copolymers with TMC when MSA is used as organocatalyst. Indeed, using MSA as catalyst and a protic initiator, exTMC and TMC show very close reactivity ratios in copolymerization reactions, leading to copolymers with high randomness (R ≈ 1) and well-controlled structures. Subsequent thiol-ene reaction on the exocyclic C=C group with thioglycolic acid or thioglycerol gives access to APCs with adjustable amounts of COOH or OH functional groups uniformly distributed along the polymer chains without requiring protection/deprotection steps.

Discussion

Monomer preparation and characterization. The most direct method to prepare exTMC reported so far consists in reacting 2-methylidene-1,3-propanediol 1 (derived from renewable glycerol xxviii,xxix ) with triphosgene in the presence of triethyl amine (24%-80% yield). xxix,xxx,xxxi However, seeking for a more sustainable procedure avoiding the use of phosgene derivatives, we decided to test the CO2-based methodology recently introduced by A. Buchard et al. xxxii,xxxiii,xxxiv,xxxv Gratifyingly, reacting 1 with tosyl chloride (TsCl) and tetramethylpiperidine (TMP) in a CO2-saturated solution of acetonitrile (1 atm) yielded exTMC of high purity (polymer-grade) in 55% isolated yield (up to about 300 mmol scale) (Figure 2a). In order to better understand the behavior of exTMC in ROP, crystals suitable for X-ray diffraction were grown and the solid-state structure of exTMC was compared with that of TMC and representative substituted 6CCs (see Figure S2). xxxvi The diffraction study revealed the typical envelope conformation of 6CCs (Figure 2b). The bending of the envelope (angle between the O1-C1-O3-O2 and C2-C3-C4-C5 mean planes, 137.8°) is very close to that of TMC (135.6°) and falls in the typical range of those observed in substituted 6CCs (126-141°). The other structural data are relatively close to those of TMC and substituted 6CCs. The main differences result from the presence of a Csp2 in the ring (C3), in particular, the endocyclic C2-C3-C4 angle. The typical values for this angle in 6CCs are in the range 105.5-107.4°, deviating only slightly from the expected 109° of a Csp3. For exTMC, the observed value (111°) shows larger deviation from the expected 120° for a Csp2. Since this constrain could affect the behavior of exTMC in ROP by impacting the ring strain, the ring-opening of exTMC by ethanol was studied by DFT calculations and the associated ΔrH (enthalpy of the ring-opening reaction) was compared to that of TMC. As model reactions, we considered the ring-opening of the H-bonded adducts between the monomer and ethanol, and referred to the most stable conformations of the ensuing products (Figure S3). xxxvi The obtained ΔrH values for the two monomers are very close (-2.3 / -3.5 kcal/mol), indicating that the presence of the C=CH2 moiety in exTMC does not induce noticeable ring strain, as to compare with TMC. Organocatalyzed Homopolymerization of exTMC. The feasibility of exTMC ROP with efficient incorporation of a protic initiator was then explored using different types of organocatalysts: TBD, DBU, TU/DBU, diphenylphosphoric acid (DPP), and MSA. Dimethoxybenzyl alcohol (DMBA) was used as the protic initiator at a monomer / initiator ratio = 30/1 and with a monomer concentration of 0.5-1 M in chloroform (Table 1).

Table 1. ROP of exTMC with different organocatalysts and DMBA as intitiator a a Reaction conditions: 0.5-1 mol/L in CDCl3 at 30 °C. b In THF with calibration over PS standards, non-corrected values. c T = 60 °C.

In all cases, the ROP occurred to give the corresponding polymer with incorporation of the initiator as the carbonate chain end (detected by 1 H NMR). However, important differences in reaction rate and control were observed. As could be expected, the polymerization is very fast with TBD at rt (30 °C) (less than 30 minutes with DMBA/TBD = 1/0.3). Using DBU alone as catalyst (DMBA/DBU = 1/0.3), the polymerization is rather slow (41 % conversion after 20h, and 80 % after 90h) but associating it to TU speeds up the reaction significantly (85% conversion within only 1h for DMBA/TU/DBU = 1/1/1). Concerning Brönsted acids, DPP is the less active of all the catalysts. Heating at 60 °C (DMBA/DPP = 1/1) was necessary to reach 92% conversion after 70h. In marked contrast, MSA (DMBA/MSA = 1/0.4) led to full conversion in 5h at 30 °C. Although this is a longer time that using TBD or TU/DBU as catalyst, NMR spectrocopy, SEC and MALDI-TOF MS analyses suggest a better control of the polymer structure (see below). SEC analysis on the polymer samples revealed Mn in the range 2800 and 3500 g/mol, depending on the organocatalyst. Notably, samples obtained with TBD or DBU as catalysts led to samples with broader dispersity (Đ 1.23 and 1.22, respectively) than those prepared with DPP or MSA (Đ 1.07 and 1.16, respectively). MSA thus appears to be a good compromise between activity and selectivity towards transfer reactions.

Homopolymer analysis: Figure 3a shows the 1 H NMR spectrum for the P(exTMC) obtained with MSA as catalyst (DP30).

The signals corresponding to the repeating OCH2 (b') and =CH2 (c') groups are observed at  4.72 and 5.45 ppm, respectively. The C=CH2 moiety is thus not affected by the polymerization process and is incorporated as is in the polymer chains (this is further confirmed by the presence of the Csp2 signals at  137.3 and 118.6 ppm in the 13 C{ 1 H} spectrum, Figure S4). The 1 H NMR spectrum shows in addition signals corresponding to the carbonate and the hydroxy chain-ends. A doublet ( 4.21 ppm, 2H, b) and a triplet ( 1.90 ppm, 1H, a) are attributed to the CH2OH chain end, whereas signals e, f, g, and h correspond to the dimethoxybenzyl carbonate chain end. The presence of these signals confirms the incorporation of the protic initiator as the carbonate chain-end. However, the integration value of the signal b corresponding to the CH2OH chain-end is higher than expected (3.2 instead of 2.0, integrals calibrated based on signal e), suggesting the presence of a second population. MALDI-TOF MS analysis (Figure 3b) shows a main population corresponding to the targeted polymer chains that contain the initiator (BDMA . nC5H6O3 + Na + ), resulting from the typical Activated-Monomer (AM) mechanism reported for ROP of cyclic monomers with MSA as catalyst. A second minor population is also observed, corresponding to telechelic polymer chains formally initiated by the 2-methylenepropanediol (H2C=C(CH2OH)2 . nC5H6O3 + Na + ). This is in fact consistent with the occurrence of some Activated-Chain-End (ACE) mechanism in competition with the desired AM, but in a minor extent (in line with the deviation of the integration value noticed by 1 H NMR for the CH2OH chain-end). Competition between these two propagating mechanisms is reminiscent of the situation we previously reported for TMC (Figure S5). S1). xxxvi As in the case of the exTMC homopolymerization, the far faster reaction occurs with TBD as catalyst (full conversion in less than 1h) and the slowest one with DPP. TU/DBU and MSA are in between, leading to full conversion in less than 5h. NMR monitoring of the copolymerization reactions was very informative concerning monomer conversions, with two different situations. The 1 H NMR spectra showed that with TBD and TU/DBU (Figure S6a for TBD), xxxvi exTMC is consumed more rapidly than TMC (TBD: 86% conversion after 20 min vs 50% for TMC; TU/DBU: 94 vs 63% after 2.5h). This behavior is in line with what has been previously reported for 4-substituted 6CCs with the same catalysts, xxiii as well as in enzymatic conditions. xxiv In marked contrast, with DPP and MSA, the conversions of the two monomers track each other (DPP: 94% and 91%, respectively, after 18h; MSA: 55% exTMC and 57% for TMC after 2.5 h, Figure S6b), xxxvi suggesting close reactivity of the two monomers. Another diagnostic data is the fact that at the end of the polymerization, the copolymer prepared with TBD as catalyst shows only TMC-hydroxyl chain-ends (Figure S6b, signal g'), xxxvi whereas the one prepared with MSA also shows some exTMChydroxyl chain-ends (Figure S7b, signal a', and discussion below). SEC analysis shows unimodal traces in all cases, but dispersity are narrower for the sample obtained with DPP (despite the higher reaction temperature, 60 °C vs rt) and MSA (Đ 1.12-1.15).

As ROCOP with MSA as organocatalyst (1.3 mol%) leads to a more random incorporation of two comonomers within the polymer chains than TBD or TU/DBU, while maintaining good control of the polymerization, the study was followed with this organocatalyst. In addition, MSA is easy to remove and is reported to be ecofriendly. xxxix In order to get higher molar masses and minimize the impact of the ACE mechanism, the diol 1,4-benzenedimethanol (BDM) was chosen to further explore the copolymerization of exTMC and TMC. ROCOP with an exTMC/TMC monomer ratio of 10/90 and increasing DP (from 15 to 120) was first explored at 1.3% catalyst loading (relative to the monomer) in 1 mol/L chloroform solutions (Table 2, entries 1-5). The exTMC content was then increased to 30-50% for a DP of 60 (Table 2, entries 6 and 7), leading to results close to those 10% content in exTMC. The ratio of functionalization can thus be easily adjusted. Conversions >96% were observed in 2-7h and the copolymers were isolated in 85-95% yields by precipitation in cold methanol after catalyst quenching with diethylisopropyl amine (DIEA). Figure 4a shows the 1 H NMR spectrum of a copolymer with DP = 60 and a TMC/exTMC monomer ratio of 50/50 (P7, Table 2, entry 7). Efficient incorporation of the difunctional initiator BDM in the core of the polymer chains is confirmed by the presence of the signals f and g, corresponding to the methylene and aromatic groups of the initiator, at  5.16 and 7.40 ppm respectively. As already observed for the copolymerization test with DMBA, two different CH2OH chain-ends are observed (b' at  3.75 ppm and d' at  4.19 ppm) corresponding to the TMC and exTMC CH2OH terminal units, respectively. Signal d' overlaps with signal b, associated with the CH2O moieties of the TMC units, which impedes accurate integration. The relative integrals of signals b, d (corresponding to the CH2O moieties of TMC and exTMC units, respectively), f and g (associated with the initiator) agree nicely with the initial monomer ratio (50/50) and monomer feed (DP60). Signals b and d are split due to the presence of homo-and heterodiades (TMC-TMC, exTMC-exTMC and TMC-exTMC sequences). The signals are very close in intensity, which denotes a high randomness of the copolymer, but accurate integration to determine the average sequence lengths (LexTMC and LTMC) was not possible due to overlapping. It was however possible using 13 C{ 1 H} NMR spectroscopy (Figure 4b), in which integration of the corresponding signals to the homo-and heterosequences was possible (after assignment of the signals by 2D NMR analysis and comparison with the respective homopolymers). The relative integrations of the signals CH2O and C=O signals give L values close to 2 for both exTMC and TMC (LexTMC = 1+IexTMC/(IexTMC+ITCM), LTMC = 1+IexTMC/(ITMC+ITCM)), which corresponds to an almost perfect randomness (R = 1/LexTMC + 1/LTMC ≈1). xli This nearly perfect randomness of the TMC/exTMC copolymer is in line with the 1 H NMR monitoring of the monomer conversions. The semi-logarithmic plot of the copolymerization reaction with a 50/50 monomer ratio and DP = 60 shows almost overlapped conversion curves for the two monomers (Figure 5a, see Figure S8 for the plot of the monomer conversions). The curves show an upward deviation from linearity (quasi zero-order in monomer rather than classical first-order) as already reported for the ROP of lactones and 6CCs with acid catalysts such as MSA or DPP, xlii,xliii,xliv,xlv and in line with the higher basicity of the carbonate moieties in the cyclic monomer compared to those of the polymer chains (due to their different conformation). xlvi In order to confirm the close reactivity of the two monomers in copolymerization, 1 H NMR monitoring was also carried out for copolymerizations with exTMC/TMC monomer ratios of 10/90 and 90/10 and DP = 60, and the relative reactivity ratios were determined for TMC and exTMC applying the Beckingham-Sanoja-Lynd (BSL) method (Figure 5b). xlvii,xlviii Whatever the monomer ratio, reactivity ratios of 0.93-0.95 and 1.04-1.07 were obtained for exTMC and TMC (see Figure S9), xxxvi respectively, confirming the very close reactivity of the two monomers and supporting the high randomness of the obtained copolymers. Figure 6 shows the linear increase of Mn with DP, up to 10800 g/mol for DP 120 (applying the correction factor reported for PTMC), xl and narrow dispersity (Đ < 1.12), supporting the possibility of adjusting the Mn of the copolymer by the monomer/initiator ratio. In order to minimize the competing ACE mechanism, two variations of the polymerization conditions were explored: (i) bulk polymerization and (ii) multi-feed of the monomers, so that the activated-monomer / monomer ratio is decreased (it is a known way to decrease the impact of the ACE mechanism). xxxvii,xxxviii Bulk polymerization (Table 2, entry 8) led to similar results than in solution. As for the multi-feed test (Table 2, entry 9), a polymerization was set up in reaction conditions similar to those of DP = 30 (Table 2, entry 2), and 3 subsequent additions of 30 equivalents each of a 10/90 mixture of comonomers (3 times at 3h time intervals, to reach DP = 120 ultimately). SEC analysis shows for the multi-feed experience an Mn of 12100 g/mol (entry 9), which is higher than the 10800 g/mol obtained for the one-feed DP = 120 (entry 5 in Table 2), while maintaining narrow dispersity. This increase of the Mn when working in multi-feed conditions is consistent with a lower impact of the competitive ACE propagation mechanism.

It is interesting to note that while performing the copolymerization reaction in bulk conditions, the formation of a eutectic melt was observed when the content in exTMC was higher than 30%. The mixture of monomers was thereupon melt at room temperature (the two monomers are white solids with Tm,TMC = 48 °C and Tm,exTMC = 53.7 °C). DSC analysis of a series of TMC/exTMC mixtures of different composition, from 90/10 to 10/90 (see Figure S11 for the stacking of the thermograms obtained at 2 °C/min), were carried out and revealed a melting point of ~14 °C for the eutectic (Figure 7) with a composition between 50/50 and 60/40 (see Figure S12 for the estimation of the eutectic composition by plotting the relative melting enthalpy of the eutectic as a function of the content in exTMC). xxxvi The formation of eutectic melts is not common in ROCOP. It was reported previously when mixing TMC with L-lactide xlix and with a 6CC deriving from desoxy-D-ribose. l Copolymerizations of exTMC and TMC were performed in bulk with propane-1,3-diol and dihydroxylated hydrogenated polybutadiene as initiators and monomer to initiator (OH group) ratios of 120 (Table 2, entries 12-14). The reactions proceeded efficiently and with good control (Ð < 1.15).

Conclusions

To conclude, we have demonstrated in this study that exTMC, a sustainable 6CC derived from glycerol and CO2, is a comonomer of choice to target random copolymerization with TMC under mild conditions. Using MSA as organocatalyst, exTMC and TMC copolymerize in a controlled manner and with relative reactivity ratios close to 1. Copolymers of well-defined structures (Mn, composition, dispersity) and high randomness can thereby be easily prepared. The methylene groups distributed along the polymer chains were then transformed by thiol-ene click reaction with thioglycolic acid or thioglycerol to give access to APCs with adjustable amounts of COOH or OH functional groups uniformly distributed along the polymer chains. Polycarbonates with highly regular distribution of functional groups along the polymer chains can be prepared in a controlled and efficient manner thanks to this approach (only 3 steps from 1, a biobased diol, and CO2), without using any protecting group. This achievement will give us the opportunity to investigate the impact of the amount and distribution (gradient vs random) of functional groups on the copolymer (APCs) properties.

Moreover, this work unveils the impact of embedding a Csp2 into a cyclic carbonate on its behavior towards Brönsted acidcatalyzed ROP. In future, we seek to take advantage of this approach to further diversify APCs by introducing substituents on the exocyclic C=C moiety.

his help on the DSC study of the TMC/exTMC eutectic. Thanks are also due to Sonia Mallet-Ladeira (ICT) for the XRD analysis of exTMC.

Figure 1 .

 1 Figure 1. Different strategies for the preparation of functionalized aliphatic polycarbonates (FG = functional group, PFG = protected functional group, ROCOP = ring-opening copolymerization).

Figure 2 .

 2 Figure 2. a) Preparation of exTMC according to two different routes. b) Molecular structure of exTMC (H-atoms, except the one at the exocyclic C=CH2 moiety, are omitted for clarity).

Figure 3 .

 3 Figure 3. 1 H NMR spectrum (CDCl3, 300 MHz) (a) and MALDI-Tof-MS analysis (b) of a PexTMC (DP = 30) prepared with MSA as catalyst

Figure 4 .

 4 Figure 4. 1 H (top) and 13 C (down) NMR spectra (CDCl3, 300 MHz) of a P(TMC-ran-exTMC) copolymer with DP = 60 and a TMC/exTMC monomer ratio of 50/50.

Figure 5 .

 5 Figure 5. (a) Semilogarithmic plots of the two monomer conversions vs reaction time, and (b) Fit of the determined reactivity ratios at different TMC/exTMC ratios (fexTMC: molar fraction of exTMC in the feed).

Figure 6 .

 6 Figure 6. Mn SEC vs. monomer/initiator ratio plot for P(TMC-ran-exTMC) copolymers with a TMC/exTMC ratio of 90/10, (red dotted line: experimental values; blue dashed line: theoretical values).

Figure 7 .

 7 Figure 7. Melting points of TMC, exTMC and their eutectic for different TMC/exTMC mixtures experimentally determined by DSC.

Figure 8 .

 8 Figure 8. a) Stacking of the 1 H NMR spectra (CDCl3, 300 MHz) of a TMC/exTMC copolymer (30% exTMC) before (bottom) and after (top) post-polymerization functionalization by thiol-ene reaction with thioglycerol. b) Overlapping of SEC traces of the corresponding copolymers.

xxxii

  McGuire, T. M.; Lopez-Vidal, E. M.; Gregory, G. L.; Buchard, A. Synthesis of 5-to 8-membered cyclic carbonates from diols and CO2: A one-step, atmospheric pressure and ambient temperature procedure. J. CO2Utiliz. 2018, 27, 283-288. xxxiii McGuire, T. M.; Pérale, C.; Castaing, R.; Kociok-Köhn, G.; Buchard, A. Divergent Catalytic Strategies for the Cis/Trans Stereoselective Ring-Opening Polymerization of a Dual Cyclic Carbonate/Olefin Monomer. J. Am. Chem. Soc. 2019, 141, 13301-13305. xxxiv For monomers deriving from CO2 and dienes/olefins, see: Tang, S.; Nozaki, K. Advances in the Synthesis of Copolymers from Carbon Dioxide, Dienes, and Olefins. Acc. Chem. Res. 2022, 55, 1524-1532. xxxv For exovinylene cyclic carbonates deriving from CO2 and propargylic alcohols, see: Ngassam Tounzoua, C.; Grignard, B.; Detrembleur, C. Exovinylene Cyclic Carbonates: Multifaceted CO2-Based Building Blocks for Modern Chemistry and Polymer Science. Angew. Chem. Int. Ed. 2022, 61, e202116066. xxxvi See Supporting Information.xxxvii Delcroix, D.; Martin-Vaca, B.; Bourissou, D.; Navarro, C. Ring-Opening Polymerization of Trimethylene Carbonate Catalyzed by Methanesulfonic Acid: Activated Monomer versus Active Chain End Mechanisms. Macromolecules 2010, 43, 8828-8835. xxxviii See also: Penczek, S.; Pretula, J. Activated Monomer Mechanism (AMM) in Cationic Ring-Opening Polymerization. The Origin of the AMM and Further Development in Polymerization of Cyclic Esters. ACS Macro Lett. 2021, 10, 1377-1397. xxxix Palden, T.; Onghena, B.; Regadío, M.; Binnemans, K. Methanesulfonic acid: a sustainable acidic solvent for recovering metals from the jarosite residue of the zinc industry. Green Chem. 2019, 21, 5394-5404. xl Palard, I.; Schappacher, M.; Belloncle, B.; Soum, A.; Guillaume, S. M. Unprecedented Polymerization of Trimethylene Carbonate Initiated by a Samarium Borohydride Complex: Mechanistic Insights and Copolymerization with ε-Caprolactone. Chem. Eur. J. 2007, 13, 1511-1521. xli Zhang, W.; Han, L.; Liu, Z.; Li, Y.; Shang, J.; Leng, X.; Li, Y.; Wei, Z. Ring opening copolymerization of -valerolactone with 2-methyl-1,3-dioxane-4-one towards poly(3-hydroxypropionate-co-5-hydroxyvalerate) copolyesters. Polym. Chem. 2022, 13, 2132-2142. xlii Batiste, D. C.; Meyersohn, M. S.; Watts, A.; Hillmyer, M. A. Efficient Polymerization of Methyl--Caprolactone Mixtures To Access Sustainable Aliphatic Polyesters. Macromolecules 2020, 53, 1795-1808. xliii Schneiderman, D. K.; Hillmyer, M. A. Aliphatic Polyester Block Polymer Design. Macromolecules 2016, 49, 2419-2428.

  xxxvi,xxxvii,xxxviii

	Run Catalyst	[exTMC]/	Time	Conv	Mn,theo Mn,SEC b Đ
			[I]/[Cat]	(h)	(%)
	1	TBD	30/1/0.3	0.5	> 96 3591	3550	1.23
	2	DBU	30/1/0.3	90	80	3591	2800	1.35
	3	TU/DBU 30/1/1/1	1.5	85	3591	3100	1.22
	4	DPP c	30/1/1	70	93	3591	2890	1.16
	5	MSA	30/1/0.4	5	96	3591	3000	1.07

Table 2 . TMC/exTMC copolymerization catalyzed by MSA: variation of DP and composition.

 2

	Entry Ref	M/I	mol%	time
	Code		exTMC	(h)

FexTMC b Mn,theo Mn,SEC c Mn,SEC d Đ c

	1	P1	15	10	2	0.092	1900	2700	1550 1.08
	2	P2	30	10	4	0.094	3400	4400	2500 1.08
	3	P3	60	10	6	0.093	6500	6410	4700 1.07
	4	P4	90	10	7	0.096	9600	10300 9100 1.08
	5	P4 120	10	7	0.092	12700	12300 10800 1.09
	6	P6	60	30	7	0.306	6500	7600	5500 1.12
	7	P7	60	50	8	0.502	6600	7200	5300 1.08
	8 d	P8 120	10	7	0.097	12700	11400 10000 1.21
	9 e	P9 120	10	8	0.092	12700	13700 12100 1.10
	10 d	P10 60	50	5	0.493	6600	7900	5800 1.09
	11	P11 120	30	7	0.299	12800	12400 10900 1.13
	12 d,f P12 120	30	3	0.289	12800	12700 11200 1.15
	13 d,f P13 120	10	3	0.093	12700	10600 9300 1.14
	14 d,g P14 120	30	5	0.287	15800	13400 11800 1.15

a Reaction conditions: 1.3 % in catalyst, 1 mol/L in CDCl3 at 30 °C; Monomer conversion > 95% (determined by 1 H NMR) for all the reactions. b Molar fraction of exTMC in the polymer determined by 1 H NMR.

c

In THF with calibration over PS standards, non-corrected values. d Values corrected using the correction factor reported for PTMC. xl d In bulk, 60 °C. e Multi-feed experiment 4×30 equiv. f With propane-1,3-diol as initiator. g With telechelic dihydroxylated hydrogenated polybutadiene (PBD H) as macroinitiator, MnPBD H = 5 600 g/mol, Đ = 1.10.

xv

  Fukushima, K. Chapter 7: ROP of Cyclic Carbonates. In Organic Catalysis for Polymerisation, The Royal Society of Chemistry: 2019, 274-327. Martin-Vaca, B.; Bourissou, D. Chapter 2: Ring-opening Polymerization Promoted by Brönsted Acid Catalysts. In Organic Catalysis for Polymerisation, The Royal Society of Chemistry: 2019, 37-86. Chen, X.; Michinobu, T. Postpolymerization Modification: A Powerful Tool for the Synthesis and Function Tuning of Stimuli-Responsive Polymers. Macromol. Chem. Phys. 2022, 223, 2100370. Durand, P. L.; Brège, A.; Chollet, G.; Grau, E.; Cramail, H. Simple and Efficient Approach toward Photosensitive Biobased Aliphatic Polycarbonate Materials. ACS Macro. Lett. 2018, 7, 250-254. Thomas, A. W.; Kuroishi, P. K.; Perez-Madrigal, M. M.; Whittaker, A. K.; Dove, A. P. Synthesis of aliphatic polycarbonates with a tunable thermal response. Polym. Chem. 2017, 8, 5082-5090. Stevens, D. M.; Tempelaar, S.; Dove, A. P.; Harth, E. Nanosponge Formation from Organocatalytically Synthesized Poly(carbonate) Copolymers. ACS Macro Lett. 2012, 1, 915-918. Tempelaar, S.; Mespouille, L.; Dubois, P.; Dove, A. P. Organocatalytic Synthesis and Post-polymerization Functionalization of Allyl-Functional Poly(carbonate)s. Macromolecules 2011, 44, 2084-2091. Similar results have been reported under enzymatic conditions. See: Al-Azemi, T. F.; Harmon, J. P.; Bisht, K. S. Enzyme-Coady, D. J.; Horn, H. W.; Jones, G. O.; Sardon, H.; Engler, A. C.; Waymouth, R. M.; Rice, J. E.; Yang, Y. Y.; Hedrick, J. L. Polymerizing Base Sensitive Cyclic Carbonates Using Acid Catalysis. ACS Macro Lett. 2013, 2, 306-312. Takata, T.; Igarashi, M.; Endo, T. Synthesis and cationic ring-opening polymerization of a cyclic carbonate, 5methylene-1,3-dioxan-2-one. J. Polym. Sci. A Polym. Chem. 1991, 29, 781-784. Painter, R. M.; Pearson, D. M.; Waymouth, R. M. Selective Catalytic Oxidation of Glycerol to Dihydroxyacetone. Shintani, R.; Moriya, K.; Hayashi, T. Guiding the nitrogen nucleophile to the middle: palladium-catalyzed decarboxylative cyclopropanation of 2-alkylidenetrimethylene carbonates with isocyanates. Chem. Commun. 2011, 47, Olsén, P.; Morvan, J.; Sawadjoon, S.; Shatskiy, A.; Johnston, E. V.; Åkermark, B. Cyclic allylic carbonates as a renewable platform for protecting chemistry in water. Green Chem. 2018, 20, 3186-3190. Zhang, S. S.; Zheng, Y. C.; Zhang, Z. W.; Chen, S. Y.; Xie, H.; Shu, B.; Song, J. L.; Liu, Y. Z.; Zeng, Y. F.; Zhang, L. Access to Branched Allylarenes via Rhodium(III)-Catalyzed C-H Allylation of (Hetero)arenes with 2-Methylidenetrimethylene Carbonate. Org. Lett. 2021, 23, 5719-5723.

	xviii Tan, L. Y.; Chanthaset, N.; Nanto, S.; Soba, R.; Nagasawa, M.; Ohno, H.; Ajiro, H. Synthesis and Preparation of Cross-
	linked Films with Ester-Free Poly(trimethylene carbonate) Bearing Aromatic Urea Moiety. Macromolecules 2021, 54,
	5518-5525.
	xxiii Pratt, R. C.; Nederberg, F.; Waymouth, R. M.; Hedrick, J. L. Tagging alcohols with cyclic carbonate: a versatile
	equivalent of (meth)acrylate for ring-opening polymerization. Chem. Commun. 2008, 114-116.
	Catalyzed Ring-Opening Copolymerization of 5-Methyl-5-benzyloxycarbonyl-1,3-dioxan-2-one (MBC) with Trimethylene
	Carbonate (TMC): Synthesis and Characterization. Biomacromolecules 2000, 1, 493-500.
	xxvii Sanda, F.; Fueki, T.; Endo, T. Cationic Ring-Opening Polymerization of an Exomethylene Group Carrying Cyclic
	Carbonate. Pseudo-Living Polymerization of 5-Methylene-1,3-dioxan-2-one by the Assistance of the Exomethylene
	Group. Macromolecules 1999, 32, 4220-4224.
	Angew. Chem. Int. Ed. 2010, 49, 9456-9459.
	3057-3059.

xvi xvii xix xx xxi xxii xxiv xxv xxvi xxviii xxix xxx xxxi

Acknowledgments

This work was supported financially by the Centre National de la Recherche Scientifique, the Université de Toulouse, NAIST institute and JSPS, Fostering Joint International Research B (JP19KK0277), The Mazda Foundation (21KK-134), CASIO SCIENCE PROMOTION FOUNDATION (39-30). M. P. acknowledges Universidad de Alcalá (Alcalá de Henares, Spain) for doctoral internship funding. K. S. acknowledges NAIST institute for Ph.D. funding. M. N. acknowledges Universidad Rey Juan Carlos (Madrid, Spain) for doctoral internship funding. Prof. Laurent Maron and Dr. Iker del Rosal (LPCNO) are kindly thanked for DFT calculations on TMC and exTMC ring-opening. Stéphane Gineste (technopolym platform of the ICT) is acknowledged for

All these results show that, thanks to the controlled character of the MSA-catalyzed copolymerization and reactivity ratios values close to 1, it is possible to prepare P(TMC-ran-exTMC) copolymers with almost perfect randomness and well-defined structures. Accordingly, copolymers with a defined content of methylidene groups distributed along the polymer chain in a highly uniform manner can be readily obtained. To illustrate the feasibility of post-polymerization functionalization, we turned to the thiol-ene reaction. xvii Reactions were carried out with two different thiols bearing non-protected protic functional groups (hydroxyl and carboxylic), namely thioglycerol and thioglycolic acid. Click addition reactions were carried out on two copolymers with DP120 and different monomer compositions (P12 and P13 with 30 and 10 % contents in exTMC, respectively) under radical conditions, using DMPA (2,2-dimethoxy-2-phenyl acetophenone) as initiator (2 wt%) and irradiation at  365 nm (Table 3). After few hours of reaction at room temperature, 1 H NMR monitoring showed almost complete disappearance of the signals at  4.70 and 5.40 ppm, corresponding to the O-CH2-C(=CH2)CH2-O sequences of the exTMC units (Figure 8a for and S13), xxxvi and the appearance of new broad multiplet signals:

(i) at  2.80, 3.50-3.60 and 3.65-3.90 ppm corresponding to the CH2 and CH groups deriving from thioglycerol (e, f and g), (ii) at  2.35 and 2.70-2.80 ppm for the new CH and CH2 groups resulting from the thio-ene addition to the C=CH2 moiety (c and d). Relative integration of signals d-g compared to signal b (non-substituted CH2 groups on the polymer backbone from TMC) shows a content in thioglycerol moiety of ~30 %. All these data are consistent with clean chemo-and regio-selective addition of the functionalized thiol to the C=CH2 moieties, without noticeable cross-linking. Moreover, SEC analysis further confirms that the thiol-ene reaction occurs without affecting the integrity of the polymer chains or causing reticulation, since Mn and Ð values are in the same range than the starting copolymers ( 3).


Carbyne anions get to work

Didier Bourissou

Laboratoire Hétérochimie Fondamentale et Appliquée, Université Paul Sabatier/ CNRS UMR 5069, 118 Route de Narbonne, 31062 Toulouse Cedex 09, France. email : didier.bourissou@univ-tlse3.fr twitter : @dbouriss, @LBPB_Lab Abstract:

The isolation of a rare example of a highly reactive low-valent carbon compound -a carbyne anion complex -enables the discovery of low-valent carbon transfer reactions.

Carbon reactive species are key intermediates in several C-C and C-X bond forming reactions -the basic transformations chemists use to build complex molecules with control of structure and functionality. Over the years, a variety of highly reactive carbon species have been isolated, or at least characterized, enabling progress in synthesis. While trivalent and divalent compounds are now well-known and quite common (Fig. 1a), related monovalent species remain extremely scant. The high degree of unsaturation further enhances the reactivity of anionic, cationic and radical centres, making them attractive species but also challenging compounds to synthesize and stabilize. In 2018, carbyne equivalents 1 (monovalent carbon species with three non-bonded electrons) were generated and their dual radical-carbene reactivity exploited to forge three covalent bonds. Now, writing in Nature Synthesis, Liu and co-workers report a new type of highly reactive carbon compounds -namely, carbyne anions -isolated as copper complexes, and their use in low-valent carbon transfer reactions. 2 Coordination of low-valent carbon species to metals, and in particular transition metals, is wellestablished for carbenes and carbynes. The stability, and hence ability to isolate such carbene and carbyne complexes resulted in their widespread use in organic and polymer synthesis -for example, as key reagents in alkene and alkyne metathesis reactions. According to bonding analysis by experimental and computational studies, the copper species prepared by Liu and co-workers are best described as anionic carbyne complexes, rather than metalla carbenes. Reactivity studies show that the complexes engage in unprecedented lowvalent carbon transfer reactions.

Design is crucial in the preparation of highly reactive compounds. In the present case, Liu and co-workers leveraged the unique ability of the -donating phosphino group to stabilize low-valent highly reactive species in their singlet state; that is, with all non-bonding electrons paired in the same orbital(s). The -donating phosphino group was first used by Bertrand and co-workers in 1988 to isolate the phosphino-silyl-carbene 3 ( i Pr2N)2P-C-SiMe3 and subsequently nitrenes 4 and phosphinidenes 5 (which are isoelectronic to carbynes).

In the method of Liu and co-workers, the carbyne anion is introduced in the coordination sphere of an electropositive metal, to bring stability while imparting C -•••M + ionic-type bonding so as to favour carbyne anion reactivity. Particularly judicious was the idea to replace gold, shown in a previous study 6 to form a metallacarbene species R2P-C-AuL, by copper (see compound 2 in Fig. 1), its lighter electropositive congener. The target complexes were obtained in three steps from the phosphino-silyl-diazo compound 1 (Fig. 1b): A first desilylation step, followed by coordination to (with two different ancillary N-heterocyclic carbene ligands) and a final step involving dinitrogen release under UV irradiation.

Using this route, the target complexes 2 were isolated in 90% yield as crystalline yellow solids. X-ray diffraction analysis showed substantial -donation from P to C, as testified by the short P=C bond length (1.541(3) Å)) and the trigonal planar environment around the P atom. The P-C-M bond angle is substantially wider in 2 than in the corresponding Au complex (164.5(2)° compared with 144.7(2)°), indicating more carbyne complex and metalla carbene structure, respectively. The electronic structure and bonding situation of the Cu and Au complexes were thoroughly analysed computationally and systematically compared. All data indicate a more ionic C•••M bonding with Cu compared with Au.

Having prepared compounds 2, Liu and co-workers investigated the possibility to achieve carbyne anion transfer reactions. Treatment with chlorotrimethylsilane resulted in the electrophilic silylation of the lowvalent carbon atom, with conversion of the carbyne anion complex 2 to a neutral phosphino-silyl-carbene 3a. Using trifluoromethanesulfonate triphenyl germane as an electrophile, the first phosphino-germylcarbene 3b was then prepared and structurally characterized. Upon treatment with methyl trifluoromethanesulfonate, MeOTf, the vinyl phosphine 4 was obtained, most likely as the result of the rearrangement by 1,2-H shift of the first-generated phosphino-methyl-carbene 7 . Finally, the carbyne anion complex 2 was found to add two equivalents of trimethylsilyl cyanide Me3Si-CN to give the ketenimine 5. It is remarkable that overall, three bonds are formed at the carbyne centre in the two latter reactions (C-H and C=CH2 for 4, C-SiMe3 and C=CNSiMe3 for 5). This work represents a real "tour de force". Free carbyne anions are extremely elusive species, with to date only few reports of their isolation and analysis in the gas phase, using collision-induced dissociation techniques. Anionic carbyne complexes are not unprecedented 8 , but none of the reported compounds showed carbyne anion reactivity as shown here. Moreover, this method enables the synthesis and isolation of a compound behaving as a carbyne anion under normal laboratory conditions, that is, on a preparative scale (up to ~ 100 mg corresponding to ~ 0.1 mmol), in the condensed phase and in the absence of oxygen and moisture.

Of course, the isolation of complexes 2 raises questions and the reported carbyne transfer reactions remain proof-of-concept transformations. More generally, it is not yet known whether complexes 2 are unique examples or the first members of a broader family. It may also be valuable to investigate if the substituent at the C atom can be modified to a functional group other than a phosphino group. In addition, it will be interesting to probe if transition metals other than Cu can be used to host and stabilize the carbyne anion. As for reactivity, the synthetically most significant transformation resulting from this work is the electrophilic functionalization of the carbyne centre to yield carbenes. In the future, the combination of anionic and carbyne features is expected to open the possibility of unprecedented transformations, from addition and insertion reactions, to small molecule and strong bond activations. It is certainly a goal to develop further carbyne anion transfer reactions and to exploit these highly reactive compounds to build complex frameworks that are inaccessible or challenging to achieve by other means.

Fig. 1 .

 1 Fig.1. Overview of the synthesis, structure and reactivity of highly reactive carbon compounds. a, The bonding arrangements of stable and highly reactive carbon compounds. A small rectangular box denotes a vacant orbital. b, Preparation and C-functionalization of the carbyne anion complex 2. Ar is either dipp or dippentp. dipp, 2,6-di-iso-propylphenyl; dipentp, 2,6-di-(3-pentanyl)phenyl; Me, methyl; Tf, trifluoromethanesulfonyl ; t Bu, tert-butyl.