Periodic Reporting for period 1 - Selective HDO (Selective sustainable hydrodeoxygenation of bioaromatics)
Reporting period: 2022-05-01 to 2024-04-30
Summary of the context and overall objectives of the project
The development of effective processes to transform non-edible biomass into base chemicals and fuels is one of the key societal challenges to achieve a low-carbon economy. Lignocellulose is an ideal renewable carbon source given its abundance on Earth. State-of-the-art lignin-first processes enable the abstract and depolymerization of lignin, delivering polyoxygenated aromatic compounds (guaiacols and syringols) with up to near-to-theoretical yields considering the percentage of the β-O-4 linkages present, and carbohydrate pulp residue which is amenable to biobased sugars. These compounds could potentially serve for the future production of bio-based aromatic and aliphatic platform chemicals. However, on one hand, accessing lower oxygen content arenes required for the chemical industry, which are traditionally obtained through oxidation of petroleum-based arenes, requires selective hydrodeoxygenation (HDO) of these bio-based polyoxygenated aromatics. Although hydrodemethoxylation can be achieved, selective hydrodehydroxylation of the OH groups while leaving the OMe group intact with high yields is only possible after converting the hydroxy into better leaving groups (–OR). However, all the known examples used traditional activating reactants (e.g. isocyanates, sulfonyl, carbamoyl or acyl chlorides, dimethoxymethylsilane), which are non-renewable, expensive, and problematic based on Environmental, Health, and Safety (EHS) criteria. Importantly, more challenging syringols, featuring 2 ortho MeO, have not yet been tackled. Selective removal of one hydroxy group in Ar-(OH)n is also unprecedented. On the other hand, current biorefineries of sugars have focused more on the energy sector by producing biofuels such as ethanol, GVL, etc, scarifying the unique enantio-enriched stereocenters, which are challenging to build artificially, gifted by nature. Selective deoxygenation of polyols with retention of stereochemistry is thus of significant importance for the further valorization of biomass. Conventional methods that meet this purpose rely on selectively transforming the hydroxy into radical precursors with unbenign activating reagents such as O-thiocarbonyl chlorides. Herein this project aims at strategies combining green activation (low cost and benign reagent) with cheap base metal catalysis featuring improved green metrics to transform biobased platform compounds selectively into functional chemicals.
Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far
1) Carbonate leaving group (LG) was introduced on phenolics under mild reaction conditions using methyl phenyl carbonate with DBU as catalyst, followed by selective hydrodeoxygenation of aryl methyl carbonates employing a heterogeneous Ni/SiO2 catalyst with HBpin in DMC solvent. The method was successfully applied to synthesize phenyl, guaiacyl and syringyl methyl carbonates, showing a broad functional group tolerance including alkyl, alkene, ether, ester, and amide delivering the hydrodeoxygenated products in moderate to high yield. Importantly, OMe groups, known as leaving groups in nickel-catalyzed hydrodemethoxylation reactions, remained intact. Furthermore, 4-propylcatechol carbonate, obtained via O-demethylation of 4-propylguaiacol and subsequent transesterification of 4-propylcatechol with DMC, was also applicable delivering a mixture of 4-propylphenol and 3-propylphenol in high yield under standard reaction conditions. Moreover, hydrodeoxygenation of 4-propylcatechol carbonate using hydrogen gas instead of HBpin was also possible by replacing DMC with propylene carbonate as a solvent. Finally, lignin oil rich in 4-propylguaiacol or 4-propylcatechol obtained via RCF of pine sawdust can also be used as feedstock, showing the robustness of the catalytic system and compatibility of our method with complex renewable mixtures.
2) A method for selective hydrodeoxygenation of arylalknanol carbonates, obtained from the reaction of arylalkanol with dimethylcarbonate using a base catalyst, was developed employing air-stable Ni(cod)(dq) in combination with NHC-ligand and HBpin reductant in ether solvent 4-MTHP. The method was successfully applied to arylalkanol methyl carbonates featuring a phenyl group positioned up to 8 methylene groups away from the carbonate leaving group. In the case of diols-derived carbonates, selective removal of the carbonate-leaving group closest to the phenyl was predominant, though overreduction to the fully deoxygenated product proved difficult. The method is also applied to enantio-enriched compounds possessing multiple stereogenic C(sp3)-O units, providing mono-deoxygenation products selectively with retention of the stereochemistry. Preliminary results with a heterogeneous catalyst showed great promise, though deoxygenation was difficult in the case of substrates where the carbonate leaving group is placed 4 or more methylene groups away from the phenyl group.
2) A method for selective hydrodeoxygenation of arylalknanol carbonates, obtained from the reaction of arylalkanol with dimethylcarbonate using a base catalyst, was developed employing air-stable Ni(cod)(dq) in combination with NHC-ligand and HBpin reductant in ether solvent 4-MTHP. The method was successfully applied to arylalkanol methyl carbonates featuring a phenyl group positioned up to 8 methylene groups away from the carbonate leaving group. In the case of diols-derived carbonates, selective removal of the carbonate-leaving group closest to the phenyl was predominant, though overreduction to the fully deoxygenated product proved difficult. The method is also applied to enantio-enriched compounds possessing multiple stereogenic C(sp3)-O units, providing mono-deoxygenation products selectively with retention of the stereochemistry. Preliminary results with a heterogeneous catalyst showed great promise, though deoxygenation was difficult in the case of substrates where the carbonate leaving group is placed 4 or more methylene groups away from the phenyl group.
Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)
Acetate is a leaving group with the potential for increased sustainability of the selective hydrodeoxygenation of biorenewable phenolics due to the low cost for installment and benign character, however, C(aryl)–O activation of aryl acetate is a long-standing challenge because of the chemoselectivity of Ar–OAc versus ArO–Ac bond cleavage. In previous work from ORSY at the University of Antwerp, steric bulky N-heterocyclic carbene ligand SIPr was discovered to promote the reactivity of nickel-catalyzed hydrodeacetoxylation using HBpin as the reductant in biorenewable solvent DMC. Ligand, solvent, and by-products, formed when NHC-salt deprotonation is involved, proved crucial to achieving high chemoselectivity for ArH over ArOH in the Ar−OAc reduction. The developed method proved broadly applicable to aromatic acetates including lignin-derivable guaiacols and syringols. Moreover, lignin oils rich in phenolic monomers are known to contain impurities such as dimers and oligomers that are difficult to separate. Hydrodeoxygenation of phenolic monomers in lignin oil can avoid the necessity of highly purified bio-derived phenolics, however, the reactivity is not guaranteed due to the impurities. A catalyst compatible with the impurities contained in lignin oil is thus of interest for a more efficient protocol. The method herein was proved to be compatible with reductive catalytic fractionation (RCF) lignin oil obtained from pine wood rich in 4-propylguaiacol, delivering fragrance component 1-methoxy-3-propylbenzene with a yield of 77% based on the 4-propylguaiacol content, showcasing a new example of producing value-added drop-in chemicals from sawdust.
In this project, alkyl carbonates (-OCO2R) have been severed as the leaving group for Ar-O cleavage which showed advantages over acetate (Ar-OAc) in terms of reactivity and chemoselectivity over undesire ArO-R cleavage due to its less electrophilic carbonyl C=O bond compared to the later. However, the installation of -OCO2R requires phosgene-based reagents such as chloroformates and dicarbonates, which does not meet the increasing expectation of a greener economy. In this regard, renewable and phosgene-free methyl phenyl carbonate (MPC) served as reagents for the installation of -OCO2Me leaving groups into phenolics including bio-based guaiacols and syringols, and dimethyl carbonate (DMC) installed cyclic carbonate for phenolics such as catechols, and pyrogallols. Heterogeneous Ni-catalyzed hydrodeoxygenation of aryl methyl carbonates (Ar-OC(O)OMe) with HBpin in a green carbonate solvent selectively delivers the corresponding deoxygenated arenes (Ar-H), leaving -OMe groups intact without arene hydrogenation. Additionally, aromatic cyclic carbonates, are also applicable and deliver the corresponding phenols. Moreover, lignin oils rich in phenolic monomers are known to contain impurities such as dimers and oligomers that are difficult to separate. Hydrodeoxygenation of phenolic monomers in lignin oil can avoid the necessity of highly purified bio-derived phenolics, however, the reactivity is not guaranteed due to the impurities. A catalyst compatible with the impurities contained in lignin oil is thus of interest for a more efficient protocol. The method herein was proved to be compatible with reductive catalytic fractionation (RCF) lignin oil obtained from pine wood rich in 4-propylguaiacol or 4-propylcatechol, delivering fragrance component 1-methoxy-3-propylbenzene or 3-propylphenol with satisfactory yields, showcasing new examples of producing value-added drop-in chemicals from sawdust.
On the other hand, methyl carbonate (-OCO2Me) is also known as a leaving group the transformation of π-conjugated C(sp3)-O bonds such as C(benzylic)-O, C(allylic)-O, etc. However, the methods for cleavage of non-π-conjugated C(sp3)-OCO2Me is not reported yet, to the best of our knowledge. In this project, -OCO2Me was easily installed onto arylalkanols with DMC using a base catalyst and served as the leaving group for C(sp3)-O cleavage. The cleavage of C(sp3)-OCO2Me is achieved by employing air-stable Ni(cod)(dq) in combination with NHC-ligand and HBpin reductant. The method was successfully applied to arylalkanol methyl carbonates featuring a phenyl group positioned up to 8 methylene groups away from the carbonate leaving group. Based on detailed experimental and DFT studies, the mechanism was proposed to proceed through initial nickel-catalyzed benzylic C-H activation followed by a metal migration toward the carbonate leaving group and a final β-oxygen elimination breaking the target C-O bond. In the case of diols-derived carbonates, selective removal of the carbonate-leaving group closest to the phenyl was predominant, though overreduction to the fully deoxygenated product proved difficult. The method is also applied to enantio-enriched compounds possessing multiple stereogenic C(sp3)-O units, providing mono-deoxygenation products selectively with retention of the stereochemistry, which showcases a new potential method for valorization of sugars.
In this project, alkyl carbonates (-OCO2R) have been severed as the leaving group for Ar-O cleavage which showed advantages over acetate (Ar-OAc) in terms of reactivity and chemoselectivity over undesire ArO-R cleavage due to its less electrophilic carbonyl C=O bond compared to the later. However, the installation of -OCO2R requires phosgene-based reagents such as chloroformates and dicarbonates, which does not meet the increasing expectation of a greener economy. In this regard, renewable and phosgene-free methyl phenyl carbonate (MPC) served as reagents for the installation of -OCO2Me leaving groups into phenolics including bio-based guaiacols and syringols, and dimethyl carbonate (DMC) installed cyclic carbonate for phenolics such as catechols, and pyrogallols. Heterogeneous Ni-catalyzed hydrodeoxygenation of aryl methyl carbonates (Ar-OC(O)OMe) with HBpin in a green carbonate solvent selectively delivers the corresponding deoxygenated arenes (Ar-H), leaving -OMe groups intact without arene hydrogenation. Additionally, aromatic cyclic carbonates, are also applicable and deliver the corresponding phenols. Moreover, lignin oils rich in phenolic monomers are known to contain impurities such as dimers and oligomers that are difficult to separate. Hydrodeoxygenation of phenolic monomers in lignin oil can avoid the necessity of highly purified bio-derived phenolics, however, the reactivity is not guaranteed due to the impurities. A catalyst compatible with the impurities contained in lignin oil is thus of interest for a more efficient protocol. The method herein was proved to be compatible with reductive catalytic fractionation (RCF) lignin oil obtained from pine wood rich in 4-propylguaiacol or 4-propylcatechol, delivering fragrance component 1-methoxy-3-propylbenzene or 3-propylphenol with satisfactory yields, showcasing new examples of producing value-added drop-in chemicals from sawdust.
On the other hand, methyl carbonate (-OCO2Me) is also known as a leaving group the transformation of π-conjugated C(sp3)-O bonds such as C(benzylic)-O, C(allylic)-O, etc. However, the methods for cleavage of non-π-conjugated C(sp3)-OCO2Me is not reported yet, to the best of our knowledge. In this project, -OCO2Me was easily installed onto arylalkanols with DMC using a base catalyst and served as the leaving group for C(sp3)-O cleavage. The cleavage of C(sp3)-OCO2Me is achieved by employing air-stable Ni(cod)(dq) in combination with NHC-ligand and HBpin reductant. The method was successfully applied to arylalkanol methyl carbonates featuring a phenyl group positioned up to 8 methylene groups away from the carbonate leaving group. Based on detailed experimental and DFT studies, the mechanism was proposed to proceed through initial nickel-catalyzed benzylic C-H activation followed by a metal migration toward the carbonate leaving group and a final β-oxygen elimination breaking the target C-O bond. In the case of diols-derived carbonates, selective removal of the carbonate-leaving group closest to the phenyl was predominant, though overreduction to the fully deoxygenated product proved difficult. The method is also applied to enantio-enriched compounds possessing multiple stereogenic C(sp3)-O units, providing mono-deoxygenation products selectively with retention of the stereochemistry, which showcases a new potential method for valorization of sugars.