Organocatalytic carbon dioxide fixation to epoxides by perfluorinated 1,3,5-triols catalysts

Abstract

In order to improve epoxides conversion to carbonates by fixation of CO₂ a new type of perfluorinated triol catalysts was developed. These simple acyclic scaffolds of enhanced acidity are efficient for catalysis through selective H-bonding activation of the epoxide. In combination with TBAI as co-catalyst, this useful transformation is performed under only 1 atmosphere of CO₂ and between 30 to 80 °C. Both the 1,3,5-triol motif and the perfluorinated side chains are crucial in order to observe this epoxide opening under such mild conditions. In addition, the stereochemistry of the starting epoxide can efficiently be conserved during the carbonate formation.

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Designing catalysts with improved activity and/or selectivity is at the heart of modern chemical research. For this purpose, chemists must identify new scaffolds possessing optimized functions and geometry for maximized efficiency in useful catalytic transformations.

The massive amount of CO₂ generated in the last decades have pushed chemists to take advantage of this chemical as an inexpensive and abundant raw material. In this context, CO₂ can be used in a circular economy platform either as an energy source through its transformation to fuels such as methanol, or as a source of bulk chemical commodities.¹ Among these, cyclic carbonates of great industrial utility can be generated by a fascinating epoxide opening with CO₂ (Scheme 1a). These carbonates can be used as alternative solvents or for the production of plastics, pharmaceuticals and other fine chemicals.² Given this industrial interest, development of new tools enabling the optimum reuse of CO₂ for the preparation of these higher value chemicals is vital.

Scheme 1 Organocatalytic epoxide opening with CO₂ and proposed catalysts.

In order to activate CO₂ towards its appropriate fixation on epoxides, tremendous efforts have been achieved to improve reaction efficiency and decrease costs and hazards.³ Progress in that direction notably imply introduction of inexpensive organocatalysts of improved catalytic activity and avoiding unnecessary toxic metals.⁴ However, despite the design of better catalysts, the challenge is to introduce alternative catalytic scaffolds enabling CO₂ fixation under exquisitely mild conditions. Most notably, simple catalytic structures enabling CO₂ activation and fixation at temperatures below 100 °C and atmospheric pressure are highly desirable for greener industrial processes and still constitutes a challenge.⁵ Given the lack of activity of numerous organocatalysts, a number of systems combining Hydrogen Bond Donor catalysts (HBD) and a quaternary ammonium salt co-catalyst have been developed. The nucleophilic counter anion of the salt acts as a temporary relay, opening the HBD-activated epoxide and serving as leaving group upon ring closure after CO₂ fixation.

For such purpose, various HBD catalysts based on different active functions such as carboxylic acids,⁶ ureas and thioureas,⁷ squaramides,⁸ phenols,⁹ silanols¹⁰ or alcohols¹¹ have been described in the last years. Among alcohol HBD, the group of Tassaing extensively studied the structure–activity relationship leading to improved catalytic efficiency (Scheme 1a). They discovered that heavily fluorinated distal 1,5-diols provided the best catalytic activity, even though high CO₂ pressure (>10 bars) was required to ensure optimum conversion.¹² In depth mechanistic studies indicated that the acidic fluorinated alcohols and the central aromatic proton were involved in the H-bond activation of epoxides. However, DFT calculations clearly indicated that the central aromatic scaffold was not optimum as observed through longer hydrogen bond between the aromatic proton and the Lewis basic oxygen atom.

In addition, in-depth analysis of alcohols acidity by the group of Kass indicated that a H-bonding cooperative effect in 1,3-polyols was responsible for enhanced acidity from a pK_a of 29.0 in the case of methanol to 19.7 for pentane-1,3,5-triol (Scheme 1b).¹³ Furthermore, insertion of CF₃ groups also considerably lowered the molecule acidity.¹⁴ Given these observations, we hypothesized that a perfluorinated 1,3,5-triol motif we recently discovered¹⁵ would provide the requisite H-bonding scaffold geometry for the critical epoxide opening and CO₂ activation. In addition, given the known anion coordination properties of such triol scaffolds, further stabilization of anionic intermediates could also facilitate the catalytic cycle (Scheme 1c).

In order to assess the feasibility of the epoxide opening under mild conditions, we tested the catalytic activity of different 1,3,5-triols using styrene oxide 1a and 1 atmosphere of CO₂ (Table 1). Under neat conditions, all three perfluorinated triols cat1–3 tested catalyzed the reaction at only 30 °C (entries 1–3). Increasing perfluorinated chains length slightly improved the conversion from 21% to 42% after only 6 hours. This result confirms the importance of the alcohol network acidity over the catalytic activity. Triol catalysts do not suffer from any deactivation and full conversion can be obtained after only 16 hours, highlighting their robustness and excellent activity under mild conditions (entry 4). In the absence of HBD catalyst, TBAI itself scarcely promotes the epoxide opening under those conditions (entry 5). Moreover, the HBD cat3 alone is also poorly efficient providing trace amount of carbonate (entry 6).

Table 1 Structure–activity relationship of different 1,3,5-triols

Entry	Catalyst	Temperature	Time	Conversion^a
Unless otherwise stated, this reaction was carried with 5 mol% of triol, 5 mol% of TBAI under an atmospheric pressure (balloon) of CO2.a Reaction conversions were obtained by ^1H NMR by determining the ratios between 1a and 2a.b In the absence of TBAI.
1	cat1	30 °C	6 h	21%
2	cat2	30 °C	6 h	36%
3	cat3	30 °C	6 h	42%
4	cat2	30 °C	16 h	>99%
5	None	30 °C	6 h	<5%
6^b	cat3	30 °C	6h	<5%
7	cat1	80 °C	6 h	75%
8	cat2	80 °C	6 h	80%
9	cat3	80 °C	6 h	85%
10	cat2	80 °C	12 h	>99%
11	cat4	80 °C	6 h	10%
12	cat5	30 °C	6 h	<5%

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In order to improve kinetics, the reaction was then performed at 80 °C. After 6 hours, good levels of conversion were obtained with cat1–3 (75–85% conversion, entries 7–9), while full conversion was attained after 12 hours (entry 10). To understand the role of the perfluorinated chain, bis-fluorohydrin triol cat4 was also tested under the same conditions.¹⁶ Even though this catalyst possessing the same central triol motif had shown good activity as HBD in Friedel–Crafts reactions, here, it provided only 10% conversion after 6 hours. Finally, non-fluorinated triol cat5 did not provide efficient epoxide activation providing only trace amount of 2a (entry 12). These results clearly demonstrate the importance of the enhanced acidity of the triol core for optimum catalytic activity.

With optimal conditions in hand, we then scrutinized the efficiency of the transformation on variously substituted epoxides (Table 2). The remarkable reactivity observed using 5 mol% of organocatalyst cat2 was further confirmed independently of the epoxide structure. In order to ascertain the impact of epoxide nature over reactivity, conversions were determined at different reaction times. Going from styrene oxide 1a to propylene oxide 1b slightly reduced reaction kinetic and full conversion were obtained after 24 h (entries 1–4). Adjacent alcohols and ethers functions were also well tolerated providing carbonates 2c–d with full conversion after 24 hours (entries 5–8). Epichlorohydrin 1e was more reactive providing 82% conversion after only 4 hours and full conversion after 12 hours (entries 9 and 10). Finally, even 1,2-disubstituted epoxides such as 1f, usually recalcitrant to opening could be converted to the corresponding carbonate with full conversion and 89% yield after 48 hours (entry 12). The tolerance of our system towards increased steric hindrance further demonstrates the efficiency of cat2 as HBD.

Table 2 Scope of the cat2-catalyzed epoxide opening

Entry	Substrate	Time	Conversion^a	Yield^b
This reaction was carried with 5 mol% of cat2, 5 mol% of TBAI under an atmospheric pressure (balloon) of CO2.a Reaction conversions were obtained by ^1H NMR.b Isolated yield. nd = not determined.c Obtained as the cis-diastereomer.
1	2a	6 h	80%	nd
2	2a	12 h	>99%	78%
3	2b	4 h	35%	nd
4	2b	24 h	99%	84%
5	2c	4 h	35%	nd
6	2c	24 h	99%	89%
7	2d	4 h	50%	nd
8	2d	24 h	99%	92%
9	2e	4 h	82%	nd
10	2e	12 h	99%	79%
11	2f	4 h	14%	nd
12	2f	48 h	99%	89%^c

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In order to get more insight on the mechanism, several control reactions were then performed (Scheme 2). Using the enantiopure epoxide (R)-1a, the stereochemical information was conserved on both starting epoxide and carbonate, indicating that the epoxide opening must occur preferentially on the primary carbon atom [(a) and (b)]. At full conversion (12 h), the enantioenriched carbonate 2a was obtained in 95% ee (a). On the other hand, starting from a racemic epoxide 1a, the enantiopure cat2* operated without enantioselectivity (c). Finally, at partial or full conversion, no resolution pathways could be observed providing either remaining epoxide or carbonate as racemates [(c) and (d)].

Scheme 2 Stereochemical outcome of the epoxide opening.

According to these experiments, the observed higher reactivity of cat2 and from previous mechanistic studies using alcohols as HBD catalysts,^7b,11,12 the reaction occurs through the synergistic role of TBAI and the 1,3,5-triol hydrogen bonding network (Scheme 3). According to the catalytic mechanism previously calculated for diols, the epoxide can be activated through simultaneous strong H-bonding interactions.¹⁷ Regioselective nucleophilic ring opening by the iodine leads to the triol-stabilized alcoholate B. Given the known anion-binding properties of cat2,¹⁵ the triol motif should stabilize the formed anion B. Subsequent addition to CO₂ provides iodo-carboxylate C, prone to cyclize forming the carbonate by iodine substitution and catalyst liberation. The improved reactivity of cat2 as compared to previous catalysts is due to the cooperativity of the acyclic triol network enhanced by the presence of the two perfluorinated chains.

Scheme 3 Proposed mechanism for the epoxide opening.

To conclude, we have demonstrated that perfluorinated triol scaffolds of appropriate geometry could be excellent catalysts for the conversion of epoxides to carbonates. In combination with TBAI as synergistic co-catalyst, under moderate temperature (30 to 80 °C) and of utmost importance using only 1 atmosphere of CO₂, full conversion to the corresponding carbonates could be observed.

In addition to the improvements it represents for this crucial reaction, this study opens the door to other related use of perfluorinated triols as organocatalysts or to a recyclable version thanks to the fluorous tag present on the catalyst structure.

Author contributions

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

Conflicts of interest

A patent on the preparation and properties of perfluorinated 1,3,5-triols has been submitted by Céline Sperandio, Jean Rodriguez and Adrien Quintard. Patent declaration. EP19 305862.5. Submitted 27 June 2019.

Acknowledgements

The Centre National de la Recherche Scientifique (CNRS) and the Aix-Marseille Université are warmly acknowledged for financial support. All technical staff from Aix-Marseille Spectropole are acknowledged for their support.

Notes and references

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17. Alternatively, a cooperative intramolecular H-bonding in the triol can increase the acidity of the catalyst favoring the epoxide activation by a single catalyst (see ref. 14).

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/d0ob00402b

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