Short Hydroacylation-Based Synthesis of Four Aryl-3-hydroxypropanones, Predictable Biomass-Derived C9 Platform Molecules
Sorbonne Université, Faculté des Sciences et Ingénierie, CNRS, Institut Parisien de Chimie Moléculaire, IPCM, 4 place Jussieu, 75005 Paris, France
Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Spielmannstrasse 7, 38106 Braunschweig, Germany
Academic Editor: Robert Wojcieszak
Special Issue: Recent Advances on Catalysis for Biomass Conversion
Received: July 22, 2022 | Accepted: October 17, 2022 | Published: October 26, 2022
Catalysis Research 2022, Volume 2, Issue 4, doi:10.21926/cr.2204036
Recommended citation: Bassoli S, Schallmey A, Oble J, Poli G, Pradal A. Short Hydroacylation-Based Synthesis of Four Aryl-3-hydroxypropanones, Predictable Biomass-Derived C9 Platform Molecules. Catalysis Research 2022;2(4):13; doi:10.21926/cr.2204036.
© 2022 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.
As the earth’s petroleum resources are becoming scarcer and scarcer, the production of bulk chemicals from renewable resources is of utmost importance for the development of new sustainable industrial processes. The most abundant carbon-based raw material is lignocellulosic biomass, which is composed of the polysaccharides cellulose and hemicellulose, as well as the aromatic-rich polymer lignin. For these three lignocellulose components, the generation and subsequent exploitation of the corresponding monomers are of high industrial relevance [1,2,3]. The isolation of cellulose and the monomerization of the two carbohydrate-based polymers into the constituent monosaccharides (or their derivatives) has been well established. However, the separation of lignin from hemicellulose and its subsequent depolymerization are much more challenging tasks . This hurdle is mainly caused by the robust and irregular structure of lignin and the presence of different types of lignin with varying ratios of guaiacyl and syringyl units, as well as linkage types present depending on the biomass source . As a result, lignin isolation and its subsequent depolymerization are hot and rapidly evolving topics . In particular, the old protocols for lignocellulosic biomass separation focused primarily on cellulose production, giving rather degraded lignins as secondary products, and vanillin as the main final monomer, which is by far the most abundant product available on the industrial scale [7,8]. Newer lignin isolation and depolymerization approaches are milder, provide more native-like lignins, and generate less degraded monomers relative to simple vanillin . Although such second-generation monomeric structures have been presently obtained only on a small scale, they may soon become potential new platform molecules for bulk or fine chemistry targets. To quickly enable follow-up synthetic studies starting from potential lignin-derived platform molecules [10,11,12] in parallel to the improvement of the efficiency and scalability of respective lignin depolymerizations, protocols for the rapid synthesis of preconized monomers and analogs are needed.
Based on the current framework for biomass valorization through C–H activation protocols [13,14,15,16,17], lignin depolymerization products as a source of renewable carbon have attracted our attention. Furthermore, several research demonstrated that biocatalytic depolymerization of lignin allowed to obtain guaiacyl-3-hydroxypropanone (GHP) and syringyl-3-hydroxypropanone (SHP) as major degradation products [18,19]. These aryl-3-hydroxypropanones appear to be ideal starting platform molecules for the synthesis of more complex value-added targets. So far, however, biocatalytic depolymerization has allowed to access only small amounts of these molecules, and the reported chemical syntheses have been very inefficient. Therefore, studies currently are underway on how to upscale the above biocatalytic depolymerizations, and obtain GHP and SHP in higher quantities. In particular, these monomers are seen as precursors for high value-added scaffolds like indanones, coumarins, flavones, xanthanes or dihydrochalcones. Thus, in the prospect that more efficient large-scale depolymerization protocols will be available in the future, it is desirable to develop modern, rapid, and efficient chemical syntheses of these aryl 3-hydroxypropanones, to enable in advance their valorization studies. Other aryl-3-hydroxypropanones are also highly desirable since they can be very interesting model substrates for those studies.
We proposed here a new, short and efficient protocol for synthesis of anisyl-3-hydroxypropanone (AHP), GHP, SHP and veratryl-3-hydroxypropanone (VHP) based on alkene hydroacylation (Figure 1).
Figure 1 The lignin depolymerization monomers synthesized in this study
2. Materials and Methods
2.1 General Information
Reactions: All reactions were carried out under an argon atmosphere by standard syringe and septa techniques. Glassware was flame-dried under vacuum or taken directly from the oven at 100°C and cooled under vacuum before use. Purifications were performed by flash column chromatography using silica gel Merck Geduran® SI 60 (40-63 μm). Yields referred to chromatographically and spectroscopically pure compounds.
Reagents and solvents: Commercial reagents were purchased from Alfa Aesar, Acros Organics, Sigma Aldrich, TCI Chemicals, Fluorochem and ABCR suppliers. Commercial solvents were purchased at Carlo Erba or VWR. Dichloromethane was dried on a Mbraun purification system MB SPS-800. THF was dried and then distilled over Na/benzophenone. Anhydrous methanol was dried appropriately and kept under inert atmosphere.
TLC: Reactions were magnetically stirred and monitored by thin layer chromatography using Merck-Kieselgel 60F254 plates and analyzed with an ultra-violet lamp (λ = 254 nm) using potassium permanganate or p-anisaldehyde as a stain.
NMR: NMR spectra (1H and 13C) were recorded on a Bruker AM 300 MHz or a Bruker AVANCE 400 MHz spectrophotometer. NMR experiments were carried out at room temperature in CDCl3, acetone-d6 and CD3OD. Chemical shifts were given in parts per million (ppm) using the solvent’s residual non-deuterated signals as reference (δ 1H = 7.26 ppm; δ 13C = 77.16 ppm for CDCl3, δ 1H = 2.05 ppm; δ 13C = 29.84 ppm and 206.26 ppm for acetone-d6, δ 1H = 3.31 ppm; δ 13C = 49.00 ppm for CD3OD). The terms m, s, d, t and q correspond to multiplet, singulet, doublet, triplet and quartet, respectively. The term br. and app. were respectively used in the case of the peak being broad or apparent, and in the latter case the correct real multiplicity cannot be surely assigned. Coupling constants (J) were given in Hertz (Hz). For previously unknown compounds, a combination of 13C DEPT, JMOD and 2D experiments (COSY, HSQC, HMBC) were used to complete the assignment of 1H and 13C signals.
IR: IR spectra were recorded with a Tensor 27 (ATR Diamond) Bruker spectrophotometer. IR spectra were reported as characteristic bands (cm-1).
HRMS: High-resolution mass spectra (HRMS) were obtained using a mass spectrometer MicroTOF from Bruker with an electron spray source (ESI) and a TOF detector at Institut Parisien de Chimie Moléculaire (FR 2769).
Melting points: Melting points were measured in capillary tubes on a Stuart Scientific SMP3 apparatus and are uncorrected.
2.2 Synthesis of Aryl-3-silylpropanones 1a-1d
2.2.1 General Procedure
A round bottom flask was charged with tris(triphenylphosphine)rhodium (I) chloride (Wilkinson’s catalyst, 5 mol%), benzoic acid (10 mol%), 2-amino-3-methylpyridine (40 mol%) and aromatic aldehyde (1.0 equiv.). The flask was sealed with a septum and placed under vacuum before being backfilled with argon. The vacuum/argon cycles were repeated twice and a 1:2 v/v mixture of dry toluene and THF (C = 1.5 M) was introduced. Dimethylphenylvinylsilane (4.0 equiv.) was added to this solution and the flask was equipped with a reflux condenser. The mixture was heated at 160°C until complete conversion was reached as checked by TLC (overnight). The crude solution was directly purified by flash column chromatography on silica gel to give the desired aryl-3-silylpropanones 1a-1d.
2.2.2 Characterization of Aryl-3-silylpropanones 1a-1d
3-(dimethyl(phenyl)silyl)-1-(4-methoxyphenyl)propan-1-one (1a). Obtained using the general procedure from 0.61 mL (5.0 mmol, 1.0 equiv.) of p-anisaldehyde. Purification by flash column chromatography on silica gel (Cyclohexane/AcOEt 9:1) gave 3-(dimethyl(phenyl)silyl)-1-(4-methoxyphenyl)propan-1-one 1a (716 mg, 48% yield) as a yellow oil.
IR (Diamond-ATR, neat, cm-1): 3033, 2857, 1734, 1636, 1583, 1514, 1255, 1139.
1H NMR (CDCl3, 300 MHz): δ = 7.97-7.79 (m, 2H, H-3 and H-5), 7.64-7.50 (m, 2H, H-13 and H-17), 7.44-7.31 (m, 3H, H-14, H-15 and H-16), 6.91 (d, J = 8.9 Hz, 2H, H-2 and H-6), 3.86 (s, 3H, H-18), 2.95-2.83 (m, 2H, H-8), 1.24-1.11 (m, 2H, H-9), 0.35 (s, 6H, H-10 and H-11).
13C NMR (CDCl3, 75 MHz): δ = 199.7 (C-7), 163.4 (C-1), 138.6 (C-12), 133.7 (2C, C-13 and C-17), 130.4 (2C, C-3 and C-5), 129.9 (C-4), 129.2 (C-15), 128.0 (2C, C-14 and C-16), 113.8 (2C, C-2 and C-6), 55.5 (C-18), 32.8 (C-9), 10.3 (C-8), -3.0 (2C, C-10 and C-11).
HRMS (ESI): m/z [M+Na]+ calcd for C18H22O2SiNa: 321.1281; found: 321.1275.
3-(dimethyl(phenyl)silyl)-1-(4-hydroxy-3-methoxyphenyl)propan-1-one (1b). Obtained using the general procedure from 456 mg (3.0 mmol, 1.0 equiv.) of vanillin. Purification by flash column chromatography on silica gel (Cyclohexane/AcOEt 9:1) gave 3-(dimethyl(phenyl)silyl)-1-(4-hydroxy-3-methoxyphenyl)propan-1-one 1b (677 mg, 72% yield) as a brown oil.
IR (Diamond-ATR, neat, cm-1): 3387, 3069, 2955, 2896, 2837, 1671, 1590, 1514, 1480, 1426, 1269.
1H NMR (CDCl3, 300 MHz): δ = 7.64-7.62 (m, 2H, H-13 and H-17), 7.52 (d, J = 1.9 Hz, 1H, H-3), 7.46 (dd, J = 8.3, 2.0 Hz, 1H, H-5), 7.43-7.35 (m, 3H, H-14, H-15 and H-16), 6.93 (d, J = 8.3 Hz, 1H, H-6), 6.62 (br s, 1H, OH), 3.88 (s, 3H, H-18), 2.98-2.83 (m, 2H, H-8), 1.27-1.10 (m, 2H, H-9), 0.37 (s, 6H, H-10 and H-11).
13C NMR (CDCl3, 75 MHz): δ = 200.0 (C-7), 150.4 (C-4), 146.8 (C-2), 138.5 (C-12), 133.6 (2C, C-14 and C-16), 129.5 (C-1), 129.1 (C-15), 127.9 (2C, C-13 and C-17), 123.3 (C-5), 113.9 (C-6), 110.1 (C-3), 56.0 (C-18), 32.6 (C-8), 10.6 (C-9), -3.1 (2C, C-10 and C-11).
HRMS (ESI): m/z [M+Na]+ calcd for C18H22SiO3Na: 337.1230; found: 337.1241.
3-(dimethyl(phenyl)silyl)-1-(4-hydroxy-3,5-dimethoxyphenyl)propan-1-one (1c). Obtained using the general procedure from 981 mg (5.0 mmol, 1.0 equiv.) of syringaldehyde. Purification by flash column chromatography on silica gel (Cyclohexane/AcOEt 1:1) gave 3-(dimethyl(phenyl)silyl)-1-(4-hydroxy-3,5-dimethoxyphenyl)propan-1-one 1c (1.43 g, 83% yield) as a brown solid.
IR (Diamond-ATR, neat, cm-1): 3328, 2974, 2902, 1658, 1578, 1518, 1465, 1454, 1334, 1223, 1107.
1H NMR (CDCl3, 300 MHz): δ = 7.58-7.51 (m, 2H, H-13 and H-17), 7.41-7.33 (m, 3H, H-14, H-15 and H-16), 7.15 (s, 2H, H-3 and H-5), 3.88 (s, 6H, H-18 and H-19), 2.92-2.80 (m, 2H, H-8), 1.21-1.11 (m, 2H, H-9), 0.34 (s, 6H, H-10 and H-11).
13C NMR (CDCl3, 75 MHz): δ = 199.8 (C-7), 146.8 (2C, C-2 and C-6), 139.6 (C-1), 138.6 (C-12), 133.7 (2C, C-13 and C-17), 129.2 (C-15), 128.2 (C-4), 128.0 (2C, C-14 and C-16), 105.6 (2C, C-3 and C-5), 56.5 (2C, C-18 and C-19), 32.7 (C-8), 10.9 (C-9), -3.0 (2C, C-10 and C-11).
HRMS (ESI): m/z [M+Na]+ calcd for C19H24O4SiNa: 367.1336; found: 367.1351.
1-(3,4-dimethoxyphenyl)-3-(dimethyl(phenyl)silyl)propan-1-one (1d). Obtained using the general procedure from 830.9 mg (5.0 mmol, 1.0 equiv.) of veratraldehyde and 2.0 mL (11.0 mmol, 2.2 equiv.) of dimethylphenylvinylsilane. Purification by flash column chromatography on silica gel (Cyclohexane/AcOEt 8:2) afforded 1-(3,4-dimethoxyphenyl)-3-(dimethyl(phenyl)silyl)propan-1-one 1d (1.52 g, 92% yield) as a colorless-yellow solid.
IR (Diamond-ATR, neat, cm-1): 3071, 3004, 1678, 1597, 1586, 1513, 1418, 1263.
1H NMR (CDCl3, 300 MHz): δ = 7.57-7.52 (m, 2H, H-13 and H-17), 7.50-7.45 (m, 2H, H-5 and H-3), 7.40-7.34 (3, 3H, H-14, H-15 and H-16), 6.84 (d, J = 8.8 Hz, 1H, H-6), 3.92 (s, 3H, H-18), 3.90 (s, 3H, H-19), 2.95-2.83 (m, 2H, H-8), 1.22-1.13 (m, 2H, H-9), 0.34 (s, 6H, H-10 and H-11).
13C NMR (CDCl3, 75 MHz): δ = 198.3 (C-7), 152.5 (C-1), 148.4 (C-2), 137.9 (C-12), 132.9 (2C, C-13 and C-17), 129.2 (C-4), 128.4 (C-15), 127.3 (2C, C-14 and C-16), 121.8 (C-5), 109.7 (C-3), 109.5 (C-6), 55.1 (C-18), 55.0 (C-19), 31.8 (C-8), 9.7 (C-9), -3.7 (2C, C-10 and C-11).
HRMS (ESI): m/z [M+Na]+ calcd for C19H24O3SiNa: 351.1387; found: 351.1390.
2.3 Synthesis of Aryl-3-hydroxypropanones 2a-2d
2.3.1 General Procedure
A round bottom flask was charged with the aryl-3-silylpropanone 1a-1d (1.0 equiv.). The flask was sealed with a septum and placed under vacuum before being backfilled with argon. The vacuum/argon cycles were repeated twice and dry dichloromethane (C = 0.16 M) was introduced. The solution was cooled to 0°C (ice/water bath) and tetrafluoroboric acid diethylether complex (2.5 equiv.) was introduced. The mixture was stirred at 0°C for 1 h and the solvent was concentrated under reduced pressure. Potassium fluoride (2.1 equiv.) and potassium bicarbonate (5.7 equiv.) were added to the residue. The mixture was placed under vacuum and backfilled with argon. It was then suspended in a 1:1 v/v mixture of THF and methanol (C = 0.08 M) and stirred at 0°C for 15 min. An aliquot of the mixture was taken to evaluate the conversion of the intermediate into the alcohol by TLC. To this suspension was introduced hydrogen peroxide (15.0 equiv., 30 wt% aqueous solution) at 0°C and the mixture was stirred until complete conversion of the intermediate was observed by TLC. The mixture was then quenched with an aqueous saturated solution of sodium sulfite followed by an aqueous solution of 1 M hydrochloric acid. The organoaqueous mixture was then poured into a separatory funnel and the mixture was extracted three times with diethyl ether. The combined organic layers were dried over anhydrous MgSO4 and filtered. The filtrate was concentrated under reduced pressure. The residue was then purified by flash column chromatography to give the desired aryl-3-hydroxypropanones 2a-2d.
2.3.2 Characterization of Aryl-3-hydroxypropanones 2a-2d
3-hydroxy-1-(4-methoxyphenyl)propan-1-one (AHP, 2a). Obtained using the general procedure from 200 mg (0.67 mmol, 1.0 equiv.) of 3-(dimethyl(phenyl)silyl)-1-(4-methoxyphenyl)propan-1-one 1a. Purification by flash column chromatography on silica gel (Cyclohexane/AcOEt 7:3 to 1:1) gave 3-hydroxy-1-(4-methoxyphenyl)propan-1-one 2a (88.8 mg, 59% yield) as colorless crystals.
IR (Diamond-ATR, neat, cm-1): 3735, 2906, 2865, 2846, 1667, 1636, 1584, 1236, 1142.
1H NMR (CDCl3, 300 MHz): δ = 7.91 (d, J = 8.9 Hz, 2H, H-3 and H-5), 6.90 (d, J = 8.9 Hz, 2H, H-2 and H-6), 3.89 (t app., J = 6.6 Hz, 2H, H-9), 3.85 (s, 3H, H-10), 3.17 (t app., J = 6.6 Hz, 2H, H-8).
13C NMR (CDCl3, 75 MHz): δ = 197.0 (C-7), 163.6 (C-1), 130.5 (2C, C-3 and C-5), 130.3 (C-4), 113.8 (2C, C-2 and C-6), 66.7 (C-9), 55.6 (C-10), 38.5 (C-8).
HRMS (ESI): m/z [M+H]+ calcd for C10H13O3: 181.0859; found: 181.0855.
3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-1-one (GHP, 2b). Obtained using the general procedure from 200 mg (0.64 mmol, 1.0 equiv.) of 3-(dimethyl(phenyl)silyl)-1-(4-hydroxy-3-methoxyphenyl)propan-1-one 1b. Purification by flash column chromatography on silica gel (CH2Cl2/MeOH 99:1) afforded 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-1-one 2b (67 mg, 54% yield) as a colorless solid.
IR (Diamond-ATR, neat, cm-1): 3360, 3280, 3009, 2920, 1671, 1591, 1518, 1484, 1464, 1451, 1424.
1H NMR (acetone-d6, 300 MHz): δ = 8.47 (br. s, 1H, OH phenol), 7.59 (dd, J = 8.2, 2.0 Hz, 1H, H-5), 7.55 (d, J = 2.0 Hz, 1H, H-3), 6.91 (d, J = 8.2 Hz, H-6), 3.96-3.88 (m, 2H, H-9), 3.90 (s, 3H, H-10), 3.65 (t, J = 5.6 Hz, 1H, OH alcohol), 3.15 (t app., J = 6.1 Hz, 2H, H-8).
13C NMR (acetone-d6, 75 MHz): δ = 198.2 (C-7), 152.4 (C-1), 148.3 (C-2), 130.7 (C-4), 124.0 (C-5), 115.4 (C-6), 111.5 (C-3), 58.7 (C-9), 56.3 (C-10), 41.5 (C-8).
HRMS (ESI): m/z [M+H]+ calcd for C10H13O4: 197.0808; found: 197.0809.
3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)propan-1-one (SHP, 2c). Obtained using the general procedure from 775 mg (2.25 mmol, 1.0 equiv.) of 3-(dimethyl(phenyl)silyl)-1-(4-hydroxy-3,5-dimethoxyphenyl)propan-1-one 1c. A portion of the product was collected by filtration after crystallization during the extraction. Purification of the concentrated and dry organic layer by flash column chromatography on silica gel (CH2Cl2/MeOH 99:1) gave 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)propan-1-one 2c (379.7 mg in total, 75% yield) as a brown solid.
IR (Diamond-ATR, neat, cm-1): 3536, 3399, 2929, 1658, 1518, 1459, 1115.
1H NMR (CD3OD, 300 MHz): δ = 7.31 (s 2H, H-3 and H-5), 3.95 (t app., 2H, H-9), 3.90 (s, 6H, H-10 and H-11), 3.18 (t app., 2H, H-8).
13C NMR (CD3OD, 75 MHz): δ = 199.7 (C-7), 149.0 (2C, C-2 and C-6), 142.5 (C-1), 129.3 (C-4), 107.3 (2C, C-3 and C-5), 58.9 (C-9), 56.9 (2C, C-10 and C-11), 41.7 (C-8).
HRMS (ESI): m/z [M+Na]+ calcd for C11H14O5Na: 249.0733; found: 249.0735.
1-(3,4-dimethoxyphenyl)-3-hydroxypropan-1-one (VHP, 2d). Obtained using the general procedure from 1.50 g (4.57 mmol, 1.0 equiv.) of 1-(3,4-dimethoxyphenyl)-3-(dimethyl(phenyl)silyl)propan-1-one 1d. Purification by flash column chromatography on silica gel (Cyclohexane/AcOEt 1:1) gave 1-(3,4-dimethoxyphenyl)-3-hydroxypropan-1-one 2d (732.0 mg, 76% yield) as a colorless solid.
IR (Diamond-ATR, neat, cm-1): 3275, 3014, 2953, 2901, 1663, 1585, 1518, 1461, 1420, 1262, 1179, 1159.
1H NMR (CDCl3, 400 MHz): δ = 7.59 (dd, J = 8.4, 2.0 Hz, 1H, H-5), 7.53 (d, J = 2.0 Hz, 1H, H-3), 6.90 (d, J = 8.4 Hz, 1H, H-6), 4.02 (q, J = 5.6 Hz, 2H, H-9), 3.95 (s, 3H, H-11), 3.94 (s, 3H, H-10), 3.20 (t app., J = 5.3 Hz, 2H, H-8), 2.71 (t, J = 6.6 Hz, 1H, OH).
13C NMR (CDCl3, 100 MHz): δ = 199.3 (C-7), 153.8 (C-1), 149.3 (C-2), 130.2 (C-4), 123.1 (C-5), 110.2 (C-6), 110.1 (C-3), 58.5 (C-9), 56.3 (C-11), 56.2 (C-10), 40.0 (C-8).
HRMS (ESI): m/z [M+H]+ calcd for C11H15O4: 211.0965; found: 211.0973.
3. Results and Discussion
Figure 2 Reported aldolisation reactions for the synthesis of GHP.
Unfortunately, but not unexpectedly , following the reaction conditions described by Ohta et al. (i.e. by deprotonating acetovanillone in the α-position of the ketone and reacting the enolate formed with formaldehyde) , we obtained the adduct from the double condensation of formaldehyde, 3, with a low 13% yield together with a trace amount of the desired GHP 2b (Figure 3). Furthermore, we tested an analogous aldol reaction starting from O-benzoyl vanillin using potassium carbonate as the base and an aqueous solution of formaldehyde, according to the protocol reported by Rosini, D’Arrigo et al. The in situ generated benzoyl-GHP was then hydrolyzed in the same pot with an aqueous solution of sodium hydroxide. Unfortunately, this protocol proved to be unsuccessful in our hands since the yield of GHP was less than 5% together with compound 3 with 7% yield, and acetovanillone was produced from the hydrolysis of the unreacted starting material (80%) .
Figure 3 Steps of GHP synthesis by reported aldolisation protocols.
In light of these unsatisfactory results, we decided to develop an original, possibly scalable, and more efficient strategy to access different aryl-3-hydroxypropanones based on a modern C–H to C–C coupling [23,24,25,26]. Inspired by previous reports of chelation-assisted alkene hydroacylation [27,28,29,30] of phenolic aldehydes, we tried to prepare the carbon skeleton of the molecules. Therefore, we developed a two-step strategy to access the desired aryl-3-hydroxypropanones. The first step consists in a Rh-catalyzed hydroacylation of aldehydes to produce aryl-3-silylpropanones, followed by a Fleming-Tamao oxidation to convert the silyl group into alcohol.
Thus, according to the protocol of C.-H. Jun et al. [27,28], treating p-anisaldehyde, vanillin, syringaldehyde, or veratraldehyde with dimethylphenylvinylsilane (4.0 equiv.) in the presence of the catalytic system [RhCl(PPh3)3 (5 mol%)/benzoic acid (10 mol%)/2-amino-3-methylpyridine (40 mol%)] at 160°C in a mixture of toluene and THF, gave the corresponding aryl-3-silyl-propanones 1a-d in moderate to excellent (1a, 48%; 1b, 72%; 1c, 83%; and 1d, 92%) yields (Table 1, entries 1-4). Besides, in the case of veratraldehyde, the amount of dimethylphenylvinylsilane could be reduced to 2.2 equivalents.
The resulting adducts were then converted into the corresponding alcohols by the Fleming-Tamao oxidation protocol (Figure 3) [31,32,33,34]. The obtained aryl-3-silylpropanones 1a-1d were then treated with: 1) tetrafluoroboric acid diethylether complex in dry dichloromethane, followed by 2) potassium fluoride and potassium bicarbonate in a 1:1 v/v mixture of THF and methanol to activate the silane, and 3) 30 wt% aqueous hydrogen peroxide solution to oxidize the activated silane intermediate. Starting from silane 1a, we obtained AHP 2a in 59% yield (Table 1, entry 1). Submission of the remaining three aryl-3-silylpropanones to the same oxidation conditions gave the desired aryl-3-hydroxypropanones 2b, 2c and 2d in moderate to good yields of 54%, 75% and 59%, respectively (Table 1, entries 2-4). Furthermore, we noted that the phenolic substrates 1b and 1c were compatible with acidic as well as oxidative conditions and did not suffer aromatic ring oxidation or degradation. In all cases, this two-step procedure provided the corresponding aryl-3-hydroxypropanones with moderate to good yields. Especially in the particular case of the synthesis of GHP (2b), this strategy was more efficient than the aldolisation method.
In summary, we reported an operationally simple and scalable two-step protocol to prepare aryl-3-hydroxypropanones, which can be regarded as second-generation lignin degradation products. Both steps rely on reported robust conditions starting from naturally occurring aromatic aldehydes. The first step consisted in the Rh-catalyzed directed C-H activation of aldehydes with dimethylphenylvinylsilane to build the entire carbon skeleton of the desired aryl-3-hydroxypropanones. This demonstrated that metal-catalyzed C-H activation protocols could be particularly powerful for the preparation of specific target molecules. The second step dealed with the oxidation of the alkylsilane formed by a Fleming oxidation procedure. Taken together, these aryl 3-hydroxypropanones are expected to be ideal starting platform molecules for the synthesis of more complex value-added targets. Future work will be dedicated to exploiting these substrates for the synthesis of different molecular scaffolds such as indanones, coumarins and flavones.
We would like to thank Claire Troufflard and Régina Maruchenko for NMR analyses and Lucrèce Matheron and Gilles Clodic for HRMS analyses.
Preliminary experiments have been performed by AP. All the experimental work was carried out by SB. Mentoring and writing/correcting the article was performed by AS, JO, GP and AP.
The authors would like to acknowledge CNRS and Sorbonne Université for financial support. SB also thanks Università dell’Insubria for a fellowship.
The authors have declared that no competing interests exist.
The following additional materials are uploaded at the page of this paper.
1. Figure S1: 1H NMR spectrum (CDCl3, 300 MHz) for compound 1a.
2. Figure S2: 13C NMR spectrum (CDCl3, 75 MHz) for compound 1a.
3. Figure S3: IR spectrum (Diamond-ATR) for compound 1a.
4. Figure S4: HRMS (ESI) for compound 1a.
5. Figure S5: 1H NMR spectrum (CDCl3, 300 MHz) for compound 1b.
6. Figure S6: 13C NMR spectrum (CDCl3, 75 MHz) for compound 1b.
7. Figure S7: IR spectrum (Diamond-ATR) for compound 1b.
8. Figure S8: HRMS (ESI) for compound 1b.
9. Figure S9: 1H NMR spectrum (CDCl3, 300 MHz) for compound 1c.
10. Figure S10: 13C NMR spectrum (CDCl3, 75 MHz) for compound 1c.
11. Figure S11: IR spectrum (Diamond-ATR) for compound 1c.
12. Figure S12: HRMS (ESI) for compound 1c.
13. Figure S13: 1H NMR spectrum (CDCl3, 300 MHz) for compound 1d.
14. Figure S14: 13C NMR spectrum (CDCl3, 75 MHz) for compound 1d.
15. Figure S15: IR spectrum (Diamond-ATR) for compound 1d.
16. Figure S16: HRMS (ESI) for compound 1d.
17. Figure S17: 1H NMR spectrum (CDCl3, 300 MHz) for compound 2a.
18. Figure S18: 13C NMR spectrum (CDCl3, 75 MHz) for compound 2a.
19. Figure S19: IR spectrum (Diamond-ATR) for compound 2a.
20. Figure S20: HRMS (ESI) for compound 2a.
21. Figure S21: 1H NMR spectrum (acetone-d6, 300 MHz) for compound 2b.
22. Figure S22: 13C NMR spectrum (acetone-d6, 75 MHz) for compound 2b.
23. Figure S23: IR spectrum (Diamond-ATR) for compound 2b.
24. Figure S24: HRMS (ESI) for compound 2b.
25. Figure S25: 1H NMR spectrum (CD3OD, 300 MHz) for compound 2c.
26. Figure S26: 13C NMR spectrum (CD3OD, 75 MHz) for compound 2c.
27. Figure S27: IR spectrum (Diamond-ATR) for compound 2c.
28. Figure S28: HRMS (ESI) for compound 2c.
29. Figure S29: 1H NMR spectrum (CDCl3, 400 MHz) for compound 2d.
30. Figure S30: 13C NMR spectrum (CDCl3, 100 MHz) for compound 2d.
31. Figure S31: IR spectrum (Diamond-ATR) for compound 2d.
32. Figure S32: HRMS (ESI) for compound 2d.
- Deneyer A, Ennaert T, Sels BF. Straightforward sustainability assessment of sugar-derived molecules from first-generation biomass. Curr Opin Green Sustain Chem. 2018; 10: 11-20. [CrossRef]
- Mika LT, Cséfalvay E, Németh Á. Catalytic conversion of carbohydrates to initial platform chemicals: Chemistry and sustainability. Chem Rev. 2018; 118: 505-613. [CrossRef]
- Fadlallah S, Roy PS, Garnier G, Saito K, Allais F. Are lignin-derived monomers and polymers truly sustainable? An in-depth green metrics calculations approach. Green Chem. 2021; 23: 1495-1535. [CrossRef]
- Sethupathy S, Murillo Morales G, Gao L, Wang H, Yang B, Jiang J, et al. Lignin valorization: Status, challenges and opportunities. Bioresour Technol. 2022; 347: 126696. [CrossRef]
- Lang JM, Shrestha UM, Dadmun M. The effect of plant source on the properties of lignin-based polyurethanes. Front Energy Res. 2018; 6: 4. [CrossRef]
- Acciardo E, Tabasso S, Cravotto G, Bensaid S. Process intensification strategies for lignin valorization. Chem Eng Process. 2022; 171: 108732. [CrossRef]
- Holladay JE, White JF, Bozell JJ, Johnson D. Top value-added chemicals from biomass. Volume II: Results of screening for potential candidates from biorefinery lignin. Richland: Pacific Northwest National Lab.; 2007. PNNL-16983. [CrossRef]
- Fache M, Boutevin B, Caillol S. Vanillin production from lignin and its use as a renewable chemical. ACS Sustain Chem Eng. 2016; 4: 35-46. [CrossRef]
- Sun Z, Fridrich B, de Santi A, Elangovan S, Barta K. Bright side of lignin depolymerization: Toward new platform chemicals. Chem Rev. 2018; 118: 614-678. [CrossRef]
- Lancefield CS, Ojo OS, Tran F, Westwood NJ. Isolation of functionalized phenolic monomers through selective oxidation and C–O bond cleavage of the β‐O‐4 linkages in lignin. Angew Chem. 2015; 127: 260-264. [CrossRef]
- Sun Z, Bottari G, Afanasenko A, Stuart MCA, Deuss PJ, Fridrich B, et al. Complete lignocellulose conversion with integrated catalyst recycling yielding valuable aromatics and fuels. Nat Catal. 2018; 1: 82-92. [CrossRef]
- Elangovan S, Afanasenko A, Haupenthal J, Sun Z, Liu Y, Hirsch AKH, et al. From wood to tetrahydro-2-benzazepines in three waste-free steps: Modular synthesis of biologically active lignin-derived scaffolds. ACS Cent Sci. 2019; 5: 1707-1716. [CrossRef]
- Pezzetta C, Veiros LF, Oble J, Poli G. Murai reaction on furfural derivatives enabled by removable N,N′-bidentate directing groups. Chem Eur J. 2017; 23: 8385-8389. [CrossRef]
- Ravasco JMJM, Monteiro CM, Siopa F, Trindade AF, Oble J, Poli G, et al. Creating diversity from biomass: A tandem bio/metal-catalysis towards chemoselective synthesis of densely substituted furans. ChemSusChem. 2019; 12: 4629-4635. [CrossRef]
- Sala R, Roudesly F, Veiros LF, Broggini G, Oble J, Poli G. Ru‐catalyzed carbonylative Murai reaction: Directed C3‐acylation of biomass‐derived 2‐formyl heteroaromatics. Adv Synth Catal. 2020; 362: 2486-2493. [CrossRef]
- Sala R, Kiala G, Veiros LF, Broggini G, Poli G, Oble J. Redox-neutral Ru(0)-catalyzed alkenylation of 2-carboxaldimine-heterocyclopentadienes. J Org Chem. 2022; 87: 4640-4648. [CrossRef]
- Mori A, Curpanen S, Pezzetta C, Perez-Luna A, Poli G, Oble J. C−H activation based functionalization of furfural derivatives. Eur J Org Chem. 2022: e202200727. doi: 10.1002/ejoc.202200727. [CrossRef]
- Ohta Y, Hasegawa R, Kurosawa K, Maeda AH, Koizumi T, Nishimura H, et al. Enzymatic specific production and chemical functionalization of phenylpropanone platform monomers from lignin. ChemSusChem. 2017; 10: 425-433. [CrossRef]
- Gall DL, Kontur WS, Lan W, Kim H, Li Y, Ralph J, et al. In vitro enzymatic depolymerization of lignin with release of syringyl, guaiacyl, and tricin units. Appl Environ Microbiol. 2018; 84. doi: 10.1128/aem.02076-17. [CrossRef]
- Ohta Y, Nishi S, Hasegawa R, Hatada Y. Combination of six enzymes of a marine Novosphingobium converts the stereoisomers of β-O-4 lignin model dimers into the respective monomers. Sci Rep. 2015; 5: 15105. [CrossRef]
- Rosini E, Allegretti C, Melis R, Cerioli L, Conti G, Pollegioni L, et al. Cascade enzymatic cleavage of the β-O-4 linkage in a lignin model compound. Catal Sci Technol. 2016; 6: 2195-2205. [CrossRef]
- Bruckner R. Organic mechanisms. Reactions, stereochemistry and synthesis. Berlin/Heidelberg: Springer; 2010. p. 568.
- Das J, Guin S, Maiti D. Diverse strategies for transition metal catalyzed distal C(sp3)-H functionalizations. Chem Sci. 2020; 11: 10887-10909. [CrossRef]
- Yang K, Song M, Liu H, Ge H. Palladium-catalyzed direct asymmetric C-H bond functionalization enabled by the directing group strategy. Chem Sci. 2020; 11: 12616-12632. [CrossRef]
- Lam NYS, Wu K, Yu JQ. Advancing the logic of chemical synthesis: C-H activation as strategic and tactical disconnections for C-C bond construction. Angew Chem. 2021; 133: 15901-15924. [CrossRef]
- Rogge T, Kaplaneris N, Chatani N, Kim J, Chang S, Punji B, et al. C–H activation. Nat Rev Methods Primers. 2021; 1: 43. [CrossRef]
- Jun CH, Lee DY, Lee H, Hong JB. A highly active catalyst system for intermolecular hydroacylation. Angew Chem Int Ed. 2000; 39: 3070-3072. [CrossRef]
- Park JW, Chang HJ, Jun CH. Rh(I)-catalyzed O-silylation of alcohol with vinylsilane. Synlett. 2006; 0771-0775. doi: 10.1055/s-2006-933129. [CrossRef]
- Dong VM, Kou KGM, Le DN. Transition-metal-catalyzed hydroacylation. In: Organic reactions. Hoboken: Wiley; 2018. pp. 231-592. [CrossRef]
- Jun CH, Moon CW, Lee DY. Chelation-assisted carbon–hydrogen and carbon–carbon bond activation by transition metal catalysts. Chem Eur J. 2002; 8: 2422-2428. [CrossRef]
- Fleming I, Henning R, Plaut H. The phenyldimethylsilyl group as a masked form of the hydroxy group. J Chem Soc Chem Commun. 1984; 29-31 [CrossRef]
- Fleming I, Henning R, Parker DC, Plaut HE, Sanderson PEJ. The phenyldimethylsilyl group as a masked hydroxy group. J Chem Soc Perkin Trans 1. 1995; 317-337. [CrossRef]
- Jones GR, Landais Y. The oxidation of the carbon-silicon bond. Tetrahedron. 1996; 52: 7599-7662. [CrossRef]
- Shintani R, Ichikawa Y, Hayashi T, Chen J, Nakao Y, Hiyama T. Catalytic asymmetric synthesis of allylsilanes through rhodium/chiral diene-catalyzed 1,4-addition of alkenyl[2-(hydroxymethyl)phenyl]dimethylsilanes. Org Lett. 2007; 9: 4643-4645. [CrossRef]