Authors: Hongji Li, Min Wang, Huifang Liu, Nengchao Luo, Jianmin Lu, Chaofeng. Zhang and Feng Wang

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1 Authors: Hongji Li, Min Wang, Huifang Liu, Nengchao Luo, Jianmin Lu, Chaofeng Zhang and Feng Wang Title: NH 2 H-Mediated Lignin Conversion to Isoxazole and Nitrile Pages: 41 Tables: 2 Figures: 10 S1

2 Supporting Information NH 2 H-Mediated Lignin Conversion to Isoxazole and Nitrile Hongji Li,, Min Wang, Huifang Liu,, Nengchao Luo,, Jianmin Lu, Chaofeng Zhang, and Feng Wang* State Key Laboratory of Catalysis, Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian , P. R. China. University of Chinese Academy of Sciences, No.19A Yuquan Road, Shijingshan District, Beijing , P. R. China. *Correspondence to: Feng Wang wangfeng@dicp.ac.cn Tel: ; Fax: S2

3 Content 1. General information Synthesis of lignin model Conversion of lignin model Control experiments and proposed pathways Extraction and transformation of birch lignin H NMR and 13 C NMR of lignin models and products Gas chromatography-mass spectrometry of transformation...36 S3

4 1. General information All chemicals were obtained from commercial suppliers, and were used without further purification. Thin-layer chromatography (TLC) was conducted with glass 0.25 mm silica gel plates. Flash chromatography columns were packed with FCP mesh silica gel in petroleum (bp C). Analysis of crude reaction mixture was done on an Agilent 7890A/5975C instrument equipped with an HP-5 MS column (30 m 0.25 mm i.d.). Naphthalene or mesitylene was used as the internal standard. Analysis condition: injector temperature, 280 C; carrier gas, helium at 1 ml/min; temperature program, firstly maintaining 100 C for 2 min, then increasing by 10 C/min to 280 C, finally maintaining 280 C for 2 min; ions were detected in full scan mode m/z Quantities of conversion, yields of guaiacol and aromatic isoxazole were using internal standard method. 1 H and 13 C NMR spectrum were measured on a Bruker AVIII 400 spectrometer ( 1 H: 400 MHz and 13 C: 101 MHz). HSQC NMR spectra were measured on a Bruker AVIII 700 MHz spectrometer. Size exclusion chromatography (SEC) YL 9110 HPLC-GPC system with Styragel columns (HR 0.5, HR 1, HR mm each) connected in series (flow rate: 1 ml/min; injection volume: 50 µl; solvent: THF (without BHT), with a UV detector (280 nm) was used. Calibration of this system used ReadyCal-Kit Poly(styrene). (MP 266, 682, 1250, 2280, 3470, 4920, 9130, 15700, 21500, 28000, 44200, Da). S4

5 2. Synthesis of lignin model 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone A 150 ml pressure bottle was charged with guaiacol (2.48 g, 20 mmol) and K 2 C 3 (3.03 g, 22 mmol) in acetone (50 ml) in Ar atmosphere and stirred at room temperature for 20 min. 2-Bromo-4-methoxy-acetophenone (4.00 g, 19 mmol) was added to this solution, the resulting suspension was stirred at room temperature for 16 h, after which the suspension was filtered and concentrated in vacuo. The solid was dissolved in ethyl acetate and washed with KH aqueous (5%, 20 ml) and water (20 ml). The organic phase was dried over anhydrous Na 2 S 4. The crude product was recrystallized from ethanol to give 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone as a white solid in 88% yield. Spectral data were in accordance with those previously reported. 1 1 H NMR (400 MHz, CDCl 3 ) δ = (m, 2H), (m, 6H), 5.27 (s, 2H), 3.87 (s, 3H), 3.86 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , , , , , , , 72.02, 55.93, phenoxy-1-phenylethanone Prepared from 2-bromoacetophenone and phenol. White solid. Spectral data were in accordance with those previously reported. 1 1 H NMR (400 MHz, CD 2 Cl 2 ) δ = (m, 2H), (m, 1H), 7.56 (dd, J=10.6 Hz, 4.8, 2H), (m, S5

6 2H), (m, 3H), 5.35 (s, 2H). 13 C NMR (101 MHz, CD 2 Cl 2 ) δ = , , , , , , , , , (2, 6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone Prepared from 2-bromo-4-methoxy-acetophenone and 2, 6-dimethoxyphenol. White solid. Spectral data were in accordance with those previously reported. 1 1 H NMR (400 MHz, CDCl 3 ) δ = (m, 2H), 6.99 (t, J=8.4 Hz, 1H), (m, 2H), 6.57 (d, J=8.4 Hz, 2H), 5.13 (s, 2H), 3.85 (s, 3H), 3.80 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ) δ = , , (2C), , (2C), , , (2C), (2C), 75.38, (2C), (3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)ethanone Prepared from 2-bromo-3,4-dimethoxyacetophenone and guaiacol. White solid. Spectral data were in accordance with those previously reported. 1 1 H NMR (400 MHz, CDCl 3 ) δ = 7.68 (dd, J=8.4, 1.9 Hz, 1H), 7.60 (d, J=1.8 Hz, 1H), (m, 1H), 6.91 (dd, J=8.0, 5.0 Hz, 2H), 6.85 (d, J=3.8 Hz, 2H), 5.29 (s, 2H), 3.94 (d, J=6.9 Hz, 6H), 3.88 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , , , , , , , , , 72.08, 56.11, 56.01, hydroxy-2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)propan-1-one S6

7 Prepared by the literature procedures. 1 To a stirring suspension of K 2 C 3 (0.55 g, 4.0 mmol) in ethanol: acetone (v/v=1:1, 20 ml) and 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone (1.13 g, 4 mmol) at 25 C, was added a water solution of formaldehyde (37%) (0.67 ml, 8.0 mmol). After 4 h the reaction mixture was filtered and was concentrated in vacuo to get a syrup product. The syrup was purified by column chromatography (petroleum ether/ethyl acetate, 1:1) to yielding 3-hydroxy-2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)propan-1-one as a little yellow solid (0.93 g, 3.1 mmol) in 77% yield. Spectral data were in accordance with those previously reported. 1 1 H NMR (400 MHz, DMS) δ = 8.07 (d, J=8.9 Hz, 2H), 7.06 (d, J=8.9 Hz, 2H), 6.96 (d, J=8.0 Hz, 1H), (m, 1H), 6.79 (dt, J=14.4, 5.0 Hz, 2H), 5.60 (t, J=4.9 Hz, 1H), 5.18 (t, J=5.8 Hz, 1H), 3.88 (t, J=5.4 Hz, 3H), 3.82 (d, J=21.6 Hz, 2H), 3.72 (d, J=16.5 Hz, 3H). 13 C NMR (101 MHz, DMS) δ = , , , , , , , , , , , 81.95, 62.89, 56.06, hydroxy-2-phenoxy-1-phenylpropan-1-one Prepared from 2-phenoxy-1-phenylethanone and formaldehyde. White solid. Spectral data were in accordance with those previously reported. 1 1 H NMR (400 MHz, DMS) δ = (m, 2H), (m, 1H), (m, 2H), (m, 2H), (m, 3H), (m, 1H), (m, 1H), 4.00 S7

8 3.81 (m, 1H). 13 C NMR (101 MHz, DMS) δ = , , , , , , , , , 81.05, (2,6-dimethoxyphenoxy)-3-hydroxy-1-(4-methoxyphenyl)propan-1-one Prepared from 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone and formaldehyde. White solid. Spectral data were in accordance with those previously reported. 2 1 H NMR (400 MHz, CD 3 CN) δ = (m, 1H), (m, 3H), 6.65 (d, J=8.4 Hz, 2H), 5.18 (dd, J=6.0, 4.2 Hz, 1H), 4.06 (q, J=7.1 Hz, 1H), 3.85 (s, 3H), (m, 2H), 3.70 (s, 6H). 13 C NMR (101 MHz, CD 3 CN) δ = , , (2C), , (2C), , , (2C), (2C), 86.24, 63.35, (2C), (3,4-dimethoxyphenyl)-3-hydroxy-2-(2-methoxyphenoxy)propan-1-one Prepared from 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)ethanone and formaldehyde. White solid. Spectral data were in accordance with those previously reported. 1 1 H NMR (400 MHz, CDCl 3 ) δ = 7.76 (dd, J=8.5, 1.9 Hz, 1H), 7.62 (d, J=1.9 Hz, 1H), (m, 1H), (m, 3H), (m, 1H), 5.41 (t, J=5.3 Hz, 1H), 5.30 (d, J=2.5 Hz, 1H), 4.08 (d, J=5.3 Hz, 2H), 3.93 (dd, J=12.0, 2.6 Hz, 6H), (m, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ = , , S8

9 150.43, , , , , (2C), , , , , 84.47, 63.74, 56.12, 55.98, hydroxy-1-(4-hydroxyphenyl)-2-(2-methoxyphenoxy)propan-1-one Prepared according to the literature. 3 To a solution of 1-(4-hydroxyphenyl)ethan-1-one (1.64 g) in ethanol was added CuBr 2 (4.5 g), the mixture was stirred at 80 C for 5 h, the product 2-bromo-1-(4-hydroxyphenyl)ethan-1-one was purified over column chromatography. 2-Methoxyphenolate was synthesized by mixing NaH with guaiacol in methanol, and the mixture was stirred overnight. The solvent was removed by evaporation and white solid was obtained. Then this white solid was mixed with 2-bromo-1-(4-hydroxyphenyl)ethan-1-one in DMF at 0 C, the mixture was stirred at room temperature for overnight. Diluted HCl aqueous was used to adjust the ph value of the solution to 3, then the solution was extracted with CHCl 3 for three times. The combined organic phase was dried by anhydrous Na 2 S 4 and filtered. The solvent was removed by evaporation and residuum was purified over column chromatography to give a white solid product. The obtained ketone model was dissolved in EtH, S9

10 followed by adding excess formaldehyde and Na 2 C 3. The solution was stirred at 50 C for 5 h. The mixture was acidized by diluted HCl and extracted by CHCl 3, the organic phase was evaporated and residuum was purified by column chromatography to give the final product. Spectral data were in accordance with those previously reported. 3 1 H NMR (400 MHz, DMS-d 6 ) δ (d, 2H), (m, 6H), (m, 1H), (m, 2H), 3.75 (s, 3H). 13 C NMR (101 MHz, DMS-d 6 ) δ , , , , (2C), , , (2C), , , , 88.11, 62.91, (2-methoxyphenoxy)-1-(4-methoxyphenyl)propane-1,3-diol Prepared from 1a according to literature. 1 A 100 ml pressure bottle was charged with 1a (604 mg, 2 mmol) and THF/water solvent (20 ml, 4:1 volume ration ) was added. NaBH 4 (152 mg, 4 mmol) was added in one portion and stirred at r.t. for 1 h. Then, an excess of saturated NH 4 Cl aqueous solution (20 ml) was added. The crude product was extracted with ethyl acetate (3 20 ml). The combined organic extracts were washed with brine (20 ml) and dried over anhydrous Na 2 S 4. The organic solvent was distilled under vacuum to 2-phenoxy-1-phenylethanol as a colourless oil. Spectral data were in accordance with those previously reported. 4 Erythro+ Threo 13 C NMR (101 MHz, CD 3 CN) δ , , , , , , , , , , , , , , , , , , , , 87.72, 85.86, 73.39, 72.92, 61.36, 56.06, S10

11 3. Conversion of lignin model A pressure bottle was charged with lignin model (0.1 mmol), hydroxylamine hydrochloride (0.3 mmol), additive (0.2 mmol), solvent (1 ml), and the reaction was conducted at 120 C under N 2 atmosphere for 12 h. After cooling to room temperature, a solution of naphthalene (300 µl, 32 mg/ml DMF) was added. The mixture was filtered and the solution was analyzed by GC-MS. The isoxazole product was identified by NMR. Pure isoxazole product was collected to act as a standard substance, and a corresponding standard work curve was made to quantify the isoxazole product after the conversion. 1 H NMR (400 MHz, MeD) δ = 8.66 (d, J=1.7 Hz, 1H), 7.80 (d, J=8.9 Hz, 2H), 7.05 (d, J=8.8 Hz, 2H), 6.85 (d, J=1.7 Hz, 1H), 3.87 (s, 3H). 13 C NMR (101 MHz, MeD) δ = , , , , , , , H NMR (400 MHz, DMS) δ = 8.94 (d, J=1.5 Hz, 1H), 7.84 (d, J=8.8 Hz, 2H), 7.08 (d, J=1.8 Hz, 2H), 7.06 (s, 1H), 3.83 (s, 3H). 13 C NMR (101 MHz, DMS) δ = , , , , , , , S11

12 S H (ppm) {8.9,160.7} {7.1,103.0} {3.8,55.7} {7.8,128.6} {7.1,114.9} N 1' 2' ' 1' 2' 1, 4 2, 3 3' 13C (ppm)

13 Table S1. Additive and solvent screening for lignin model conversion. a Entry Additive Solvent Conve rsion (%) Yield of isoxazole (%) Yield of nitrile (%) Yield of ester (%) Yield of guaiacol 1 None MeH < Ac 2 MeH < H 2 C 2 4 MeH < CF 3 S 3 H MeH Na 2 C 3 MeH Et 3 N MeH KH MeH < FeCl 3 MeH 92 < AlCl 3 MeH C 3 F 9 9 S 3 Yb (%) MeH < Zn MeH Mg MeH Mo 3 MeH 83 < Zr 2 MeH < Mg DMF < Mg CH 3 CN < Mg Toluene < Mg EtH < Mg Dichlor oethane <1 24 a Conditions: 1a (0.1 mmol), hydroxylamine hydrochloride (3 equiv), additive (2 equiv), solvent (1 ml), N 2 (1 atm), 120 C, 12 h, and GC yields. S13

14 Table S2. The amount of Mg on the conversion of lignin model. a H Mg + HNH 2 HCl MeH, N 2, 120 o C N + N + H + Entry Amount of Mg (equiv) Conversi on (%) Yield of isoxazole (%) Yield of nitrile (%) Yield of ester (%) Yield of guaiacol (%) < < < < < <1 83 a Conditions: 1a (0.1 mmol), hydroxylamine hydrochloride (3 equiv), methanol (1 ml), N 2 (1 atm), 120 C, 12 h, and GC yields. Figure S1. Gas chromatography analysis of reaction mixture at 2 min for the system of lignin model/nh 2 H HCl/Mg at 120 C in ethanol. A.u. denotes arbitral unit. S14

15 LHJ_01 #1027 RT: 2.16 AV: 1 NL: 2.17E2 T: ITMS - p ESI Full ms @cid25.00 [ ] Relative Abundance m/z Figure S2. Mass spectra of intermediate (M = 193) detected by LTQ rbitrap Elite (ESI, negative ion mode, M-1). Scheme S1. Conversion of lignin model to isoxazole and guaiacol using hydroxylamine--sulfonic acid (SA). Conditions: 1a (0.1 mmol), HS 3 --NH 2 (3 equiv), EtH (1 ml), N 2 (1 atm), 120 C, 12 h, and GC yields. Scheme S2. Conversion of phenolic lignin model to isoxazole and guaiacol. Conditions: 1a (0.1 mmol), hydroxylamine hydrochloride (3 equiv), EtH (1 ml), N 2 (1 atm), 120 C, 12 h, and GC yields. S15

16 4. Control experiments and proposed pathways Compounds 1-phenylprop-2-en-1-one and oxiran-2-yl(phenyl)methanone were synthesized by the literature procedures. 2, 5 1-Phenylprop-2-en-1-one, 1 H NMR (400 MHz, CDCl 3 ) δ = 7.95 (dt, J=8.5, 1.7 Hz, 2H), (m, 1H), (m, 2H), 7.16 (dd, J=17.1, 10.6 Hz, 1H), 6.44 (dd, J=17.1, 1.7 Hz, 1H), 5.94 (dd, J=10.6, 1.7 Hz, 1H). 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , , xiran-2-yl(phenyl)methanone, 1 H NMR (400 MHz, CDCl 3 ) δ = 8.05 (m, 2H), (m, 1H), (m, 2H), 4.25 (dd, J=4.5, 2.5 Hz, 1H), 3.13 (dd, J=6.5, 4.5 Hz, 1H), 2.97 (dd, J=6.5, 2.5 Hz, 1H). 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , 51.09, The direct conversion of lignin model to (4-methoxyphenyl)(oxiran-2-yl)methanone was not possible without NH 2 H through the control experiments (eq S1 and eq S2). We deduced that (Z)-oxiran oxime, not the oxiran ketone, was the potential intermediate. When 1-phenylprop-2-en-1-one was S16

17 selected as the substrate, only 27% yield of isoxazole and 9% yield of nitrile were obtained. Therefore, the possibility of ketene as intermediate can be excluded. Scheme S3. Possible pathways for reaction of lignin model with hydroxylamine. To reveal the promoting effect on isoxazole formation by other metal oxides, herein we conducted a control experiments. In view of that only Zn gave a similar but moderate isoxazole yield as Mg, we conducted same control experiment for Zn as Mg. Results were presented in equation S4. Similar isoxazole yield using ZnCl 2 in equation S4 was obtained as in Figure 1 using Zn. The result proved that Zn has a similar promoting effect with Mg for isoxazole formation, which is that Zn releases NH 2 H as an HCl-binding reagent, which promotes oximation reaction, and then to form ZnCl 2 which catalyzes the formation of isoxazole. S17

18 To reveal the effect of sulfonic type additives on bond cleavage of lignin model, we conducted the acidolysis reaction of 1a in the presence of trifluoromethane sulfonic acid (CFS) without NH 2 H (eq S5). Interestingly, the ether bond was readily cleaved and gave (4-methoxyphenyl)(oxiran-2-yl)methanone as the main product. Therefore the addition of acid can efficiently promote cleavage of oxidized lignin model. 5. Extraction and transformation of birch lignin 5.1 Extraction, pre-oxidation, and transformation procedure of birch lignin. To birch sawdust (40 g) was added 1, 4-dioxane (200 ml) followed by 2 M HCl (16 ml), then the mixture was heated at 120 C under N 2 atmosphere for 2.5 h. The mixture was cooled and filtrated using Buchner funnel. The collected liquid was partially concentrated in vacuo and precipitated by water (200 ml). The precipitated raw lignin was dried in vacuo at 60 C. Then acetone: methanol (9:1, 10 ml) was used to dissolve the raw lignin. The liquid was precipitated by diethyl ether (200 ml). The fine lignin was collected by filtration using Buchner funnel and dried in vacuo to give a birch lignin (3.0 g). To a solution of birch lignin (1.2 g) in 2-methoxyethanol/1,2-dimethoxyethane (2:3, 17 ml) was added DDQ (120 mg, 10 wt%) and t BuN (105 µl). 6 The mixture was stirred at 80 C under 2 atmosphere (balloon) for 14 hours. The solution was S18

19 precipitated by Et 2 (160 ml). The oxidized lignin was collected by filtration using Buchner funnel and dried in vacuo. A pressure bottle was charged with oxidized birch lignin (70 mg), hydroxylamine hydrochloride (49 mg) or hydroxylamine--sulfonic acid (79 mg), Mg (9 mg), Yb(CF 3 S 3 ) 3 (49 mg) or CF 3 S 3 H (47 µl), solvent (2.5 ml), and the reaction was conducted at 120 C under N 2 atmosphere for 12 h. After cooling to room temperature, a solution of naphthalene (200 µl, 32 mg/ml DMF) was added. The mixture was filtered using filter membrane and the solution was analyzed by GC-MS. For identifying of isoxazole structure after conversion, the internal standard was not added. The solvent of reaction mixture was removed in vacuo. Residues were dissolved in DMS-d 6 and filtered using filter membrane. The filtrate was analyzed by 2D HSQC NMR. Figure S3. Extraction and transformation procedure of birch lignin. S19

20 5.2 Characterization of dioxosolv birch lignin before and after oxidation. The 1 H, 13 C-HSQC spectra was acquired using standard Bruker pulse sequence hsqcetgpsp data points was acquired over 12 ppm spectral width (acquisition time 60.8 ms) in F2 dimension. 256 increments were acquired in the F1 dimension (acquisition time 3.63 ms) with a spectral width of 200 ppm centered on 95 ppm. The total experiment for one sample was 20 min. (a) (b) Aγ A'γ Aα Aβ A'β 80 Aβ A'β H (ppm) Figure S4. 2D HSQC NMR (aliphatic region) of dioxasolv birch lignin before (a) and after oxidation (b). Here we used the number of β--4 linkages per C9 unit to calculate the β--4 content of the isolated lignin and oxidized lignin as reported before. 6 We measured the volume integrals of various cross peaks in 2D HSQC spectra of sample. For example, we quantified the integral value of β-proton in β--4, and then integrated the S/G/H-proton in aromatic region. The label of each peak was affirmed according to S20

21 previous works. 7 After that we can calculate the total C9 units per β--4 linkage. From this data we calculated the number of β--4 linkages per C9 unit. Finally, the numbers of β--4 linkages per C9 unit of isolated lignin and oxidized lignin is 0.44 and 0.37, respectively. Therefore the contents of β--4 linkages in isolated lignin and oxidized lignin are 44% and 37%, respectively. Figure S5. 2D HSQC NMR (aromatic region) of dioxasolv birch lignin before (a) and after oxidation (b). S21

22 5.3 Hydroxylamine mediated conversion of lignin. (a) (b) (c) 13C (ppm) (d) (e) 13C (ppm) Figure S6. 2D HSQC spectra of (a) isoxazole monomer, (b) birch lignin, (c) oxidized birch lignin after reaction with Yb(CF 3 S 3 ) 3 /HNH 2 HCl for 14 h, (d) oxidized birch lignin after reaction with CF 3 S 3 H/HNH 2 HCl for 14 h, and (e) oxidized birch lignin after reaction with hydroxylamine--sulfonic acid for 14 h. S22

23 Figure S7. GC-MS of mixture after conversion of oxidized birch lignin using Mg/HNH 2 HCl. S23

24 5.4 SEC spectra of birch lignin, oxidized lignin and reaction mixuture Size-exclusion chromatography was used to assess the molecular weight distribution before oxidation, after oxidation, and especially after depolymerization. All the samples, including dioxasolv birch lignin, oxidized lignin and reaction mixture with HA, were soluble in THF (1 mg sample in 1mL THF). The dioxasolv birch lignin had a major fraction with a molecular weight of 2664 Da (M w ) (Figure S8). Compared with initial lignin, oxidized lignin had some fractions with the molecular weight higher than 3098 Da (M w ), which suggested the lignin may undergo partial re-condensation during oxidation (Figure S9). After reaction with hydroxylamine hydrochloride, the major fraction (60%) with a molecular weight of 1921 Da (M w ) and monomeric fraction (20%, molecular weight less than 350 Da) indicated that lignin was efficiently depolymerized under this system (Figure S10). Figure S8. SEC diagram of dioxasolv birch lignin. S24

25 Figure S9. SEC diagram of oxidized birch lignin. Figure S10. SEC diagram of reaction mixture with HA. S25

26 6. 1 H NMR and 13 C NMR of lignin models and products 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl) ethanone S26

27 1-(4-methoxyphenyl)-3-hydroxy-2-(2-methoxyphenoxy)propan-1-one H 3 C H CH f1 (ppm) S27

28 2-phenoxy-1-phenylethanone S28

29 S29 3-hydroxy-2-phenoxy-1-phenylpropan-1-one H (ppm) H C (ppm) H

30 2-(2, 6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone H 3C CH 3 CH H (ppm) H 3C CH 3 CH C (ppm) S30

31 2-(2,6-dimethoxyphenoxy)-3-hydroxy-1-(4-methoxyphenyl)propan-1-one H 3C H CH 3 CH H (ppm) H 3 C H CH 3 CH C (ppm) S31

32 S32 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)ethanone H (ppm) C (ppm)

33 S33 1-(3,4-dimethoxyphenyl)-3-hydroxy-2-(2-methoxyphenoxy)propan-1-one H (ppm) H C (ppm) H

34 S34 1-phenylprop-2-en-1-one oxiran-2-yl(phenyl)methanone C (ppm) C (ppm)

35 3-(4-methoxyphenyl)isoxazole S35

36 7. Gas chromatography-mass spectrometry of transformation S36

37 S37

38 S38

39 S39

40 S40

41 References 1. Dawange, M.; Galkin, M. V.; Samec, J. S. M., ChemCatChem 2015, 7, Forkel, N. V.; Henderson, D. A.; Fuchter, M. J., Tetrahedron Lett. 2014, 55, Zhu, C.; Ding, W.; Shen, T.; Tang, C.; Sun, C.; Xu, S.; Chen, Y.; Wu, J.; Ying, H., ChemSusChem 2015, 8, Bardet, M.; Lundquist, K.; Parkas, J.; Robert, D.; von Unge, S., Magn. Reson. Chem. 2006, 44, Chanthamath, S.; Takaki, S.; Shibatomi, K.; Iwasa, S., Angew. Chem. Int. Ed. 2013, 52, Lancefield, C. S.; jo,. S.; Tran, F.; Westwood, N. J., Angew. Chem. Int. Ed. 2015, 54, Mansfield, S. D.; Kim, H.; Lu, F.; Ralph, J., Nat Protoc 2012, 7, S41