Enantioselective Oxidation of Alkenes with Potassium Permanganate Catalyzed by Chiral Dicationic Bisguanidinium

Enantioselective Oxidation of Alkenes with Potassium Permanganate Catalyzed by Chiral Dicationic Bisguanidinium Chao Wang*, Lili Zong, Choon-Hong Tan* Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21Nanyang Link, Singapore 637371 Table of contents Materials and Methods.....(S2) Preparation and Structure of Bisguanidinium Catalysts...(S3) Investigation of Asymmetric Permanganate Oxidation Conditions.....(S4) Configuration Determination of Substrates and Products....(S6) Mechanistic Investigation.... (S8) Preparation and Characterization of Catalysts...... (S11) Preparation and Characterization of Substrates.. (S15) General Methods for Asymmetric Permanganate Oxidation..... (S24) Reduction of Oxohydroxylation Product 6a..... (S26) Characterization of Asymmetric Permanganate Dihydroxylation Product....(S27) Characterization of Asymmetric Permanganate Oxohydroxylation Product...(S31) References......(S36) X-ray Crystal Data.........(S37) Selected NMR Spectra and HPLC Traces.....(S39) S1

Materials and Methods General 1 H and 13 C NMR spectra were recorded on Bruker Avance III 400 (400MHz) (100 MHz) spectrometer. Chemical shifts are recorded as δ in units of parts per million (ppm). The residual solvent peak was used as an internal reference. 19 F NMR was performed on a Bruker Avance III 400 (400MHz) spectrometer. High resolution mass spectra (HRMS) were obtained on the Q-Tof Premier mass spectrometer (Waters Corporation) and reported in units of mass of charge ratio (m/z). Enantiomeric excess values were determined by chiral HPLC analysis on Shimadzu LC-20AT and LC-2010CHT HPLC workstations. Optical rotations were measured in ethyl acetate using a 1 ml cell with a 1 dm path length on a Jasco P-1030 polarimeter with a sodium lamp of wavelength 589 nm and reported as follows: [a] D rt (c = g/100 ml, solvent). Melting points (mp) were measured in Opti Melt MPA100 equipment and uncorrected. IR spectra were recorded with neat solid/liquid samples on a Shimadzu IR- Prestige-21 spectrometer and reported in wave numbers (cm -1 ). X-ray crystallography analysis was performed on Bruker X8 APEX X-ray diffraction meter. Flash chromatography separations were performed on Merck 60 (0.040-0.063mm) mesh silica gel. Analytical thin-layer chromatography (TLC) was performed on Merck 60 F254 silica gel plates. Visualization was performed using a UV lamp or potassium permanganate stain or p-anisaldehyde stain. Materials THF were distilled over sodium/benzophenone under N2 atmosphere. Toluene, Acetonitrile and Dichloromethane were distilled over CaH2 under N2 atmosphere. Aryl acetates were purchased from commercial suppliers. Aryl ketoesters were prepared from aryl bromides according to reported literature 1. Wittig reagents were purchased from commercial suppliers or prepared from alkyl bromides according to reported literature 2. Potassium permanganate was ground into fine powder before use. Tetrabutylammonium permanganate was prepared according to literature 3. All racemates were prepared with stoichiometric amount of tetrabutylammonium bromide. Solvents for asymmetric permanganate oxidation reaction were commercial grade and used as supplied without further purification. S2

Preparation and Structure of Chiral Dicationic Bisguanidinium Catalysts Figure S1. Synthetic Protocol for Bisguanidinium Catalysts. a, Preparation of bisguanidinium catalyst in three steps from commercial available chiral diamine. b, Bisguanidinium catalysts structure. S3

Investigation of Asymmetric Permanganate Oxidation Conditions Table S1. Screening of Asymmetric Permanganate Dihydroxylation Conditions a entry catalyst temperature solvent additive b ee of 2a c 1 BG-I 0 TBME aq. NaHCO 3 50% 2 BG-I -40 TBME aq. NaHCO 3 56% 3 BG-I -40 TBME H 2 O 64% 4 BG-I -60 TBME H 2 O 71% 5 BG-I -60 PhCH 3 H 2 O 45% 6 BG-I -60 DCM H 2 O 26% 7 BG-I -60 THF H 2 O 9% 8 BG-I -60 TBME aq. KI 75% 9 BG-I -60 TBME 0.1 N aq. HCl 72% 10 BG-I -60 TBME aq. NaH 2 PO 4 61% 11 BG-I -60 TBME aq. K 3 PO 4 ND 12 BG-I -60 TBME aq. NH 4 Cl 73% 13 BG-I -60 TBME aq. MgSO 4 69% 14 BG-I -60 TBME aq. K 2 CO 3 65% 15 BG-V -60 TBME aq. KI 90% 16 BG-V -60 TBME H 2 O 64% 17 BG-II -60 TBME 20 wt% aq. KI 88% 18 BG-III -60 TBME 20 wt% aq. KI 85% 19 BG-IV -60 TBME 20 wt% aq. KI 92% 20 BG-IV -60 TBME 0 wt% aq. KI 73% 21 BG-IV -60 TBME 0.4 wt% aq. KI d 75% 22 BG-IV -60 TBME 5 wt% aq. KI 91.4% 23 BG-IV -60 TBME 10 wt% aq. KI 92.2% 24 BG-IV -60 TBME 20 wt% aq. KI 92.5% 25 BG-IV -60 TBME 40 wt% aq. KI 92.2% a The reaction was conducted on 0.025 mmol scale in 0.5 ml solvent with 0.05 ml aqueous additive. b All the aqueous additives were used as saturated solution unless otherwise noted. c Ee was determined by chiral HPLC. d 0.4 wt% aq. KI corresponds to 5 mol%. N.D. not determined. S4

Figure S2. Investigation of Electron-deficient Aryl and Alkyl Substituted Acrylates. The reaction was conducted on 0.025 mmol scale in 0.5 ml TBME with 0.05 ml aqueous additive. Ee was determined by chiral HPLC. Table S2. Screening of Asymmetric Permanganate Oxidation Conditions for Enoate 4a a entry catalyst additive b 4a:(5a+5a ):6a:3g c ee of 5a/5a d ee of 6a d 1 BG-I H 2 O 25:30:0:45 78/69 N.D. 2 BG-IV H 2 O 17:33:0:50 84/89 N.D. 3 BG-III H 2 O 8:38:0:54 91/94 N.D. 4 BG-IV 5 wt% aq. KI N.D. N.D. N.D. 5 BG-IV 0.4 wt% aq. KI 8:30:0:62 92/90 N.D. 6 BG-III 1N aq. KOH 4:36:0:60 90/93 N.D. 7 BG-III aq. NaHCO 3 2:41:0:57 91/94 N.D. 8 BG-III 1N aq. HCl 11:32:41:16 85/93 92 9 BG-III 0.1N aq. HCl 14:26:5:55 88/92 N.D. 10 BG-III aq. NH 4 Cl 9:30:6:55 90/92 N.D. 11 BG-III AcOH 85% e N.D. 92 12 BG-III H 2 O/AcOH 90% e N.D. 92 a The reaction was conducted on 0.05 mmol scale in 1 ml TBME and 0.05 ml aqueous additive. b All the aqueous additives were used as saturated solution unless otherwise noted. c Ratios were determined according to crude 1 H NMR analysis. d Ee was determined by chiral HPLC. e Isolated yield of 6a. N.D. not determined. S5

Table S3. Screening of Organic Acid Under Oxohydroxylation Condition a entry acid additive conversion b ee of 6r c 1 AcOH (3.5 equiv.) 72% 78% 2 (3.5 equiv) 81% 71% 3 (3.5 equiv) 83% 68% 4 PhCOOH (3.5 equiv) 80% 68% 5 CF 3 COOH (3.5 equiv) 50% 85% 6 AcOH (20 equiv) 77% 55% a The reaction was conducted on 0.05 mmol scale for 48 hours in 1 ml TBME and 0.05 ml water. b Conversions were determined according to crude 1 H NMR analysis. c Ee was determined by chiral HPLC. Configuration Determination of Substrates and Products Figure S3. Determination of Geometrical Configuration of Trisubstituted Enoates. Generally, the chemical shift of alkene H in E-enoates showed higher ppm than Z- enoates. The Z, E configuration of other trisubstituted enoates was determined based on this assumption. CCDC 1061539 for (E)-4p. S6

Figure S4. Determination of Absolute Configuration of Chiral Diols. The absolute configuration of all other oxidation products was determined by analogy. CCDC 1061538 for (R)-S1, CCDC 1061540 for (2R, 3S)-S2, CCDC 1061541 for 5a. S7

Mechanistic Investigation Figure S5. Control Experiments to Test the Possibility of Oxidizing Diol 5a to Ketone 6a. These results ruled out the possibility of in situ oxidation of dihydroxylation product to generate oxohydroxylation product. Figure S6. Control Experiments to Test the Possibility of E, Z Isomerization Under Asymmetric Permanganate Oxidation Condition. These results ruled out E/Z isomerization of enoates under the permanganate oxidation conditions and suggested comparable level of asymmetric induction for both E, Z-enoates. S8

Catalyst Stability Investigation In order to test the stability of the catalyst under KMnO4 oxidation condition, we performed the following experiment. To the bisguanidinium catalyst BG-III (0.0034 mmol, 5 mg) in tert-butyl methyl ether (1 ml) was added KMnO4 (0.17 mmol, 26 mg, 50 equiv.) in one portion. The resulting mixture was stirred vigorously at room temperature for 1 h. Then it was quenched by drops of saturated Na2S2O3 solution and extracted with Et2O (2 2 ml). The combined organic extracts were dried with Na2SO4, and concentrated under reduced pressure. The crude residue was characterized by 19 F NMR analysis. Only one main peak ( = -119.74) was found which is identical to the bisguanidinium catalyst. Figure S7. Investigation of Stability of Bisguanidinium Catalysts (BG-III) Under KMnO 4 Oxidation Condition. S9

Anion Exchange and Counteranion Effects We performed anion exchange experiments with BG-III[2Cl - ]. We found that the counteranion [Cl - ] can be easily changed into [I - ] or [BArF - ] by stirring the BG-III[2Cl - ] with KI or NaBArF in DCM at room temperature. The reaction was monitored by TLC. Surprisingly, after anion exchange, the TLC polarity of BG-III[2I - ] and BG-III[2BArF - ] is much smaller than BG-III[2Cl - ]. BG-III[2I - ] and BG-III[2BArF - ] was purified by column chromatography on silica gel. 1 H NMR analysis confirmed that both chloride anions were exchanged in BG-III [2BArF - ]. We then performed asymmetric dihydroxylation of 1a with BG-III[2I - ] and found that higher ee was obtained than with BG-III[2Cl - ]. Figure S8. Anion Exchange of Bisguanidinium Catalysts BG-III and Evaluation of BG-III[2I - ] Under Dihydroxylation Condition. S10

Preparation and Characterization of Bisguanidinium Catalysts Preparation of catalyst BG-I as the representative example: 1,4-bis((4S,5S)-1,3-bis(3,5-di-tert-butylbenzyl)-4,5-diphenylimidazolidin-2-ylidene) piperazine-1,4-diium chloride (BG-I): Thiourea S3 was prepared according to literature procedure 4. A 25 ml RBF was charged with a solution of thiourea S3 (1.59 g, 2.41 mmol, 1.0 equiv) in toluene (8 ml) with a condenser under N2 atmosphere. (COCl)2 (1.66 ml, 19.3 mmol, 8.0 equiv) was added via syringe in one portion. The mixture was heated to 90 o C for about 12 h, and then refluxed for 1 h. Toluene was removed under reduced pressure and solid imidazoline salt was obtained directly for the next step without any purification. The imidazoline salt was dissolved in dry MeCN (2 ml) under nitrogen atmosphere, and then piperazine (62 mg, 0.72 mmol, 0.3 equiv) was added, followed by the addition of Et3N (1 ml, 7.23 mmol, 3.0 equiv). Then the whole solution was heated to reflux for 12 h and cooled to rt. Add 1M HCl (20 ml) to the reaction solution and the mixture was extracted by CH2Cl2 (20 ml 3). Solvent was removed under reduced pressure and bis-guanidinium salt BG-I was obtained by flash chromatography (silica gel, DCM-Methanol 100:1-30:1), as a beige powder, 695 mg, 68% yield. Other fluorinated bisguanidinium catalysts were prepared following similar procedure from the corresponding thiourea. BG-I: 1 H NMR (400 MHz, CDCl3) δ 7.30 (dd, J = 5.0, 1.5 Hz, 12H), 7.20 (s, 4H), 7.05 (dd, J = 6.5, 2.8 Hz, 8H), 6.96 (d, J = 1.5 Hz, 8H), 5.19 (d, J = 14.7 Hz, 4H), 4.82 (d, J = 14.7 Hz, 4H), 4.73 (d, J = 9.5 Hz, 4H), 4.48 (d, J = 9.5 Hz, 4H), 4.32 (s, 4H), 1.14 (s, 72H); 13 C NMR (100 MHz, CDCl3) δ 162.68, 151.30, 137.67, 131.89, 129.58, 129.16, 126.51, 123.37, 122.26, 70.39, 54.52, 48.99, 34.69, 31.37, 31.28; HRMS (ESI) calcd for C94H124Cl2N6 m/z [M-2Cl - ] 2+ : 668.4944; found: 668.4941. S11

Preparation of sidearm of fluorinated bisguanidinium catalysts 1,5-di-tert-butyl-2-fluoro-3-methylbenzene (o-f, S4) and 1,3-di-tert-butyl-2-fluoro-5- methylbenzene (p-f, S4 ): To a solution of 3, 5-di-tert-butyl toluene (4.08 g, 20 mmol, 1.0 equiv) in MeCN (40 ml) were added Selectfluor (10.6 g, 30.0 mmol, 1.5 equiv) at room temperature and then the reaction mixture was stirred at 82 C for 12 h. The solvent was removed under reduced pressure and then hexane (100 ml) was added to the concentrated residue. Insoluble material was filtered off, and then the filtrate was concentrated. The crude product were purified by flash chromatography over silica gel (hexane as the eluent) to give the mixed compounds 1,5-di-tert-butyl-2-fluoro-3- methylbenzene (o-f, S4) and 1,3-di-tert-butyl-2-fluoro-5-methylbenzene (p-f, S4 ) in a ratio of 5:1, as colorless oil, 3.5 g, in 79% yield. Fluorinated products were identified by 1 H NMR analysis and the ratio of them was confirmed by 1 HNMR analysis. 1-(bromomethyl)-3,5-di-tert-butyl-2-fluorobenzene (S5) and 5-(bromomethyl)-1,3-ditert-butyl-2-fluorobenzene (S5 ): To a solution of the mixed compounds S2 and S2 (3.5 g, 15.8 mmol, 1.0 equiv) in DCE (15.8 ml) were added BPO (191mg, 0.79 mmol, 0.05 equiv) and NBS (3.08 g, 17.3 mmol, 1.1 equiv) at room temperature and then the reaction mixture was stirred at 84 C for 42 h. The solvent was removed under reduced pressure and then hexane (80 ml) was added to the concentrated residue. Insoluble material was filtered off, and then the filtrate was concentrated. The crude product were purified by flash chromatography over silica gel (hexane as the eluent) to give the mixed compounds 1-(bromomethyl)-3,5-di-tert-butyl-2-fluorobenzene and 5-(bromomethyl)-1,3-di-tertbutyl-2-fluorobenzene as colorless oil, 4.7 g, in quantitative yield. Products were identified by 1 H NMR analysis. 3,5-di-tert-butyl-2-fluorobenzyl acetate (S6) and 3,5-di-tert-butyl-4-fluorobenzyl acetate (S6 ): To a solution of the mixed compounds (4.7 g, 15.8 mmol, 1.0 equiv) in DMF (15.8 ml) were added CsOAc (15.16 g, 79.0 mmol, 5.0 equiv) at room temperature and then the reaction mixture was stirred at 60 C for 12 h. The solvent was removed under vacuum pump and water was added to the concentrated residue. The mixture was S12

extracted with hexane and the organic layer was washed with brine, dried over aqueous Na2SO4. The solvent was evaporated, and the crude residue was purified by flash chromatography over silica gel (hexane: ethyl acetate = 1:20 as the eluent) to give the mixed acetate compounds, as colorless oil, 3.97 g, in 84% yield. (3, 5-di-tert-butyl-2-fluorophenyl)methanol (S7): To a solution of the obtained acetates mixture (3.97 g, 13.2 mmol, 1.0 equiv) in MeOH (130 ml) was added K2CO3 (912 mg, 6.6 mmol, 0.5 equiv) and then the reaction mixture was vigorously stirred at room temperature for 12 h as monitored by thin-layer chromatography (TLC). Methanol was removed under reduced pressure and water was added to the concentrated residue. The mixture was extracted with hexane and the organic layer was washed with brine, dried over aqueous Na2SO4. The solvent was evaporated, and the crude residue was purified by flash chromatography over silica gel to afford the desired compounds in 83% total yield. It is noteworthy that these two alcohols can be separated by carefully running the flash chromatography over silica gel. (3, 5-di-tert-butyl-2-fluorophenyl)methanol was obtained as colorless oil, 2.391 g, in 76% yield. 1 H NMR (400 MHz, CDCl3) δ 7.27 (s, 1H), 7.26 (s, 1H), 4.74 (d, J = 1.0 Hz, 2H), 1.39 (d, J = 0.9 Hz, 9H), 1.32 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 157.89 (d, J = 246.5 Hz), 146.12 (d, J = 3.8 Hz), 136.05 (d, J = 11.7 Hz), 127.38 (d, J = 16.8 Hz), 123.94 (d, J = 4.8 Hz), 123.75 (d, J = 6.2 Hz), 60.26 (d, J = 6.7 Hz), 34.59, 34.50 (d, J = 2.4 Hz), 31.54, 30.05 (d, J = 3.5 Hz); 19 F NMR (376 MHz, CDCl3) δ -121.97. 1-(bromomethyl)-3,5-di-tert-butyl-2-fluorobenzene (S5) : (3,5-di-tert-butyl-2- fluorophenyl)methanol S7 (2.391 g, 10.0 mmol, 1.0 equiv.) was suspended in a vigorously stirred solution of glacial AcOH (20 ml) and HBr (48% wt in H2O, 11.4 ml, 10 equiv.). The suspension was heated up to 100 C for 2 h. Then the mixture was cooled to room temperature and poured on ice-water and stirred again for 10 min. The mixture was extracted with ether, and the organic solution was washed with brine, dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The residue was subjected to flash chromatography using hexane as an eluent to afford the product 1- (bromomethyl)-3,5-di-tert-butyl-2-fluorobenzene) as colourless oil, 2.82 g, in 94% yield. 1 H NMR (400 MHz, CDCl3) δ 7.30 (dd, J = 7.6, 2.5 Hz, 1H), 7.23 (dd, J = 6.5, 2.5 Hz, 1H), 4.54 (d, J = 1.4 Hz, 2H), 1.40 (d, J = 0.9 Hz, 9H), 1.32 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 157.89 (d, J = 250.8 Hz), 146.27 (d, J = 3.9 Hz), 136.56 (d, J = 11.7 Hz), 125.64 (d, J = 3.2 Hz), 125.02 (d, J = 6.2 Hz), 124.66 (d, J = 16.5 Hz), 34.58 (d, J = 2.7 Hz), 34.56, 31.46, 29.99 (d, J = 3.6 Hz), 27.15 (d, J = 7.2 Hz); 19 F NMR (376 MHz, CDCl3) δ -118.83. S13

BG-II: 1 H NMR (400 MHz, CDCl3) δ 7.39 7.28 (m, 12H), 6.98 (dd, J = 6.3, 2.7 Hz, 8H), 6.93 (d, J = 6.8 Hz, 8H), 5.30 (d, J = 14.1 Hz, 4H), 4.91 (d, J = 9.7 Hz, 4H), 4.79 (d, J = 14.1 Hz, 4H), 4.54 (d, J = 9.5 Hz, 4H), 4.13 (s, 4H), 1.20 (s, 72H); 13 C NMR (100 MHz, CDCl3) δ 162.54, 162.25, 160.02, 138.16, 137.92, 137.78, 129.64, 129.27, 126.68, 126.61, 126.11, 70.06, 54.24, 48.70, 34.45, 29.94, 29.91; 19 F NMR (376 MHz, CDCl3) δ - 106.44; HRMS (ESI) calcd for C94H120F4Cl2N6 m/z [M-2Cl - ] 2+ : 704.4755, found: 704.4758. BG-III: 1 H NMR (400 MHz, CDCl3) δ 7.25 7.16 (m, 12H), 7.16 7.07 (m, 4H), 7.01 (d, J = 4.7 Hz, 8H), 6.76 6.59 (m, 4H), 5.21 (d, J = 14.4 Hz, 4H), 4.74 (d, J = 9.8 Hz, 4H), 4.57 (d, J = 14.3 Hz, 4H), 4.47 (d, J = 10.1 Hz, 4H), 4.28 (d, J = 20.2 Hz, 4H), 1.28 (s, 36H), 1.07 (s, 36H); 13 C NMR (100 MHz, CDCl3) δ 163.12, 159.51, 157.06, 146.50, 146.47, 136.35, 136.32, 136.21, 129.25, 128.96, 127.21, 127.18, 126.93, 125.31, 125.25, 119.23, 119.06, 70.07, 49.96, 48.81, 48.78, 34.39, 34.37, 34.32, 31.16, 29.90, 29.88; 19 F NMR (376 MHz, CDCl3) δ -119.54; HRMS (ESI) calcd for C94H120F4Cl2N6 m/z [M-2Cl - ] 2+ : 704.4755, found: 704.4760. BG-IV: 1 H NMR (400 MHz, CDCl3) δ 7.29 7.23 (m, 12H), 7.16 (dd, J = 7.7, 2.0 Hz, 2H), 7.03 (d, J = 3.1 Hz, 4H), 7.01 6.94 (m, 4H), 6.91 (d, J = 6.8 Hz, 4H), 6.86 6.75 (m, 2H), 5.23 (d, J = 14.2 Hz, 4H), 4.94 4.57 (m, 8H), 4.48 (s, 4H), 4.31 4.25 (m, S14

4H), 1.26 (s, 18H), 1.20 (s, 36H), 1.13 (s, 18H); 13 C NMR (100 MHz, CDCl3) δ 163.04, 162.43, 159.91, 159.60, 157.14, 146.65, 146.62, 137.91, 137.77, 137.29, 136.98, 136.34, 136.22, 129.41, 129.36, 129.13, 129.08, 127.30, 127.27, 126.74, 126.57, 126.41, 126.34, 125.46, 125.40, 119.18, 119.02, 70.85, 69.59, 54.09, 49.29, 48.87, 34.45, 34.44, 34.42, 31.27, 29.95, 29.92; 19 F NMR (376 MHz, CDCl3) δ -106.55, -119.36; HRMS (ESI) calcd for C94H120F4Cl2N6 m/z [M-2Cl - ] 2+ : 704.4755, found: 704.4758. Preparation and Characterization of Substrates Terminal substrates are prepared from aryl acetate ester. Methylenation of aryl acetate esters is according to previously reported procedure 5. Hydrolysis of 2-arylacrylate to corresponding 2-arylacrylic acid followed a reported procedure 6. tert-butyl esters were prepared from 2-arylacrylic acid using di-tert-butyl dicarbonate. Trisubstituted substrates were obtained from aryl ketoesters through Wittig reaction. Preparation and characterization of terminal substrates Preparation of tert-butyl 2-phenylacrylate from 2-phenylacrylic acid: To a solution of 2-phenylacrylic acid (148 mg, 1 mmol), di-tert-butyl dicarbonate (330 mg, 1.5 mmol) in 2 ml dichloromethane was added with triethylamine (115 ul, 1 mmol). The resulting solution was added carefully with DMAP (48 mg, 0.4 mmol) at room temperature and then stirred overnight. After removing solvent, the reaction was directly charged to column chromatography affording tert-butyl 2-phenylacrylate as colorless oil (194 mg, 95% yield). tert-butyl 2-phenylacrylate (1a): 1 H NMR (400 MHz, CDCl3) δ 7.44 7.38 (m, 2H), 7.33 (dd, J = 4.2, 3.4 Hz, 3H), 6.24 (d, J = 1.4 Hz, 1H), 5.82 (d, J = 1.4 Hz, 1H), 1.53 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 166.07, 142.93, 137.13, 128.31, 127.95, 127.88, 125.49, 81.26, 28.07; HRMS (ESI) calcd for C13H16O2 m/z [M+H] + : 205.1229; found: 205.1227. tert-butyl 2-(p-tolyl)acrylate (1b): 1 H NMR (400 MHz, CDCl3) δ 7.43 7.33 (m, 2H), 6.94 6.80 (m, 2H), 6.15 (d, J = 1.4 Hz, 1H), 5.76 (d, J = 1.4 Hz, 1H), 3.82 (s, 3H), 1.54 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 166.33, 159.40, 142.23, 129.56, 129.48, 123.97, 113.37, 81.12, 55.23, 28.06; HRMS (ESI) calcd for C14H18O2 m/z [M+H] + : 219.1385; found: 219.1381. S15

tert-butyl 2-(m-tolyl)acrylate (1c): 1 H NMR (400 MHz, CDCl3) δ 7.29 7.19 (m, 3H), 7.19 7.06 (m, 1H), 6.23 (d, J = 1.4 Hz, 1H), 5.81 (d, J = 1.4 Hz, 1H), 2.38 (s, 3H), 1.55 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 166.12, 142.98, 137.45, 137.03, 128.97, 128.62, 127.82, 125.40, 125.21, 81.12, 28.04, 21.38; HRMS (ESI) calcd for C14H18O2 m/z [M+H] + : 219.1385; found: 219.1389. tert-butyl 2-(4-ethylphenyl)acrylate (1d): 1 H NMR (400 MHz, CDCl3) δ 7.39 7.30 (m, 2H), 7.18 (d, J = 8.2 Hz, 2H), 6.20 (d, J = 1.4 Hz, 1H), 5.80 (d, J = 1.4 Hz, 1H), 2.66 (q, J = 7.6 Hz, 2H), 1.54 (s, 9H), 1.25 (t, J = 7.6 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 166.23, 144.03, 142.75, 134.42, 128.22, 127.45, 124.69, 81.11, 28.54, 28.06, 15.44; HRMS (ESI) calcd for C15H20O2 m/z [M+H] + : 233.1542; found: 233.1545. tert-butyl 2-([1,1'-biphenyl]-4-yl)acrylate (1e): 1 H NMR (400 MHz, CDCl3) δ 7.61 (dd, J = 9.9, 8.0 Hz, 4H), 7.52 (d, J = 8.1 Hz, 2H), 7.46 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.3 Hz, 1H), 6.29 (s, 1H), 5.90 (s, 1H), 1.57 (s, 9H) 13 C NMR (100 MHz, CDCl3) δ 166.03, 142.45, 140.75, 140.70, 136.03, 128.75, 128.73, 127.34, 127.05, 126.70, 125.39, 81.33, 28.08; HRMS (ESI) calcd for C19H20O2 m/z [M+H] + : 285.1542; found: 285.1540. tert-butyl 2-(4-methoxyphenyl)acrylate (1f): 1 H NMR (400 MHz, CDCl3) δ 7.43 7.31 (m, 2H), 6.92 6.83 (m, 2H), 6.16 (d, J = 1.2 Hz, 1H), 5.76 (d, J = 1.3 Hz, 1H), 3.81 (s, 3H), 1.54 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 166.30, 159.39, 142.23, 129.54, 129.44, 123.90, 113.35, 81.07, 55.19, 28.03; HRMS (ESI) calcd for C14H18O3 m/z [M+H] + : 235.1334; found: 235.1331. tert-butyl 2-(3-methoxyphenyl)acrylate (1g): 1 H NMR (400 MHz, CDCl3) δ 7.26 (dd, J = 8.9, 7.0 Hz, 1H), 7.04 6.91 (m, 2H), 6.90 6.79 (m, 1H), 6.23 (d, J = 1.4 Hz, 1H), 5.82 (d, J = 1.4 Hz, 1H), 3.82 (s, 3H), 1.53 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 165.95, 159.16, 142.79, 138.44, 128.90, 125.54, 120.81, 114.02, 113.47, 81.26, 55.20, 28.06; HRMS (ESI) calcd for C14H18O3 m/z [M+H] + : 235.1334; found: 235.1333. S16

tert-butyl 2-(4-(methylthio)phenyl)acrylate (1h): 1 H NMR (400 MHz, CDCl3) δ 7.38 7.31 (m, 2H), 7.25 7.19 (m, 2H), 6.21 (d, J = 1.2 Hz, 1H), 5.79 (d, J = 1.2 Hz, 1H), 2.48 (s, 3H), 1.53 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 165.96, 142.23, 138.36, 133.82, 128.67, 125.95, 124.94, 81.28, 28.04, 15.68; HRMS (ESI) calcd for C14H18O2S m/z [M+H] + : 251.1106; found: 251.1102. tert-butyl 2-(3,4-dimethylphenyl)acrylate (1i): 1 H NMR (400 MHz, CDCl3) δ 7.24 (s, 1H), 7.20 (d, J = 7.9 Hz, 1H), 7.14 (d, J = 7.8 Hz, 1H), 6.21 (d, J = 1.0 Hz, 1H), 5.81 (d, J = 1.3 Hz, 1H), 2.31 (s, 3H), 2.30 (s, 3H), 1.58 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 166.22, 142.79, 136.31, 135.95, 134.60, 129.40, 129.18, 125.67, 124.43, 80.96, 28.01, 19.71, 19.39; HRMS (ESI) calcd for C15H20O2 m/z [M+H] + : 233.1542; found: 233.1541. tert-butyl 2-(benzo[d][1,3]dioxol-5-yl)acrylate (1j): 1 H NMR (400 MHz, CDCl3) δ 6.95 6.85 (m, 2H), 6.78 (d, J = 8.0 Hz, 1H), 6.15 (d, J = 1.3 Hz, 1H), 5.96 (s, 2H), 5.74 (d, J = 1.3 Hz, 1H), 1.53 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 166.11, 147.40, 147.24, 142.32, 131.09, 124.47, 122.05, 108.87, 107.84, 101.05, 81.26, 28.05; HRMS (ESI) calcd for C14H16O4 m/z [M+H] + : 249.1127; found: 249.1124. tert-butyl 2-(3,5-dimethoxyphenyl)acrylate (1k): 1 H NMR (400 MHz, CDCl3) δ 6.57 (d, J = 2.3 Hz, 2H), 6.44 (t, J = 2.3 Hz, 1H), 6.21 (d, J = 1.3 Hz, 1H), 5.81 (d, J = 1.3 Hz, 1H), 3.79 (s, 6H), 1.53 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 165.87, 160.27, 142.89, 138.99, 125.51, 106.58, 100.14, 81.25, 55.29, 28.05; HRMS (ESI) calcd for C15H20O4 m/z [M+H] + : 265.1440; found: 265.1439. S17

Preparation and characterization of trisubstituted substrates Figure S9. Preparation and The Z, E Ratio of Trisubstituted Enoates. The Z, E ratio of trisubstituted enoates was determined by 1 H NMR analysis. S18

Preparation of tert-butyl 2-(3-methoxyphenyl)but-2-enoate from tert-butyl 2-(3- methoxyphenyl)-2-oxoacetate: To a suspension of ethyltriphenylphosphonium bromide (3.6 mmol) in dry THF (7 ml) at 0 o C was added dropwise with n-butyllithium (3.5 mmol). After stirring at 0 o C for 1h, tert-butyl 2-(3-methoxyphenyl)-2-oxoacetate (3 mmol) in 1 ml THF was added to the stirred reaction mixture. The reaction was then allowed to warm to room temperature. After confirming completion of the reaction by TLC, water was added to quench the reaction. The organic layer was extracted with ethyl acetate and then combined and concentrated. After column chromatography with hexane / ethyl acetate (30:1), Z, E mixture of tert-butyl 2-(3-methoxyphenyl)but-2-enoate was obtained as an oil (75% yield). tert-butyl 2-(3-methoxyphenyl)but-2-enoate (4a): 1 H NMR (400 MHz, CDCl3) δ 7.27 (t, J = 7.9 Hz, 1H), 7.03 (q, J = 7.2 Hz, 1H), 6.93 6.72 (m, 3H), 3.81 (s, 3H), 1.73 (d, J = 7.2 Hz, 3H), 1.47 (s, 9H) for E-4a; δ 7.22 (t, J = 8.0 Hz, 1H), 6.93 6.72 (m, 3H), 6.16 (q, J = 7.2 Hz, 1H), 3.80 (s, 3H), 1.98 (d, J = 7.2 Hz, 3H), 1.55 (s, 9H) for Z-4a; 13 C NMR (100 MHz, CDCl3) δ 167.74, 166.26, 159.41, 159.08, 139.29, 138.43, 136.93, 136.87, 136.23, 131.19, 129.16, 128.76, 122.31, 119.22, 115.50, 112.94, 112.58, 112.29, 81.47, 80.53, 55.15, 28.21, 28.09, 15.61, 15.42 for Z, E mixture of 4a; HRMS (ESI) calcd for C15H20O3 m/z [M+H] + : 249.1491; found: 249.1487. tert-butyl 2-(3-methoxyphenyl)pent-2-enoate (4b): 1 H NMR (400 MHz, CDCl3) δ 7.25 (t, J = 7.9 Hz, 1H), 6.90 (t, J = 7.7 Hz, 1H), 6.85 6.81 (m, 1H), 6.75 (d, J = 7.5 Hz, 1H), 6.71 (dd, J = 2.4, 1.6 Hz, 1H), 3.80 (s, 3H), 2.08 (p, J = 7.6 Hz, 2H), 1.47 (s, 9H), 1.01 (t, J = 7.5 Hz, 3H) for E-4b; 13 C NMR (100 MHz, CDCl3) δ 166.45, 159.05, 145.04, 137.19, 134.75, 128.71, 122.21, 115.41, 112.56, 80.56, 55.15, 28.09, 22.89, 13.42 for E-4b; HRMS (ESI) calcd for C16H22O3 m/z [M+H] + : 263.1647; found: 263.1653. tert-butyl 2-(3-methoxyphenyl)hex-2-enoate (4c): 1 H NMR (400 MHz, CDCl3) δ 7.25 (t, J = 7.9 Hz, 1H), 6.93 (t, J = 7.7 Hz, 1H), 6.86 6.81 (m, 1H), 6.78 6.69 (m, 2H), 3.80 (s, 3H), 2.06 (dd, J = 15.0, 7.5 Hz, 2H), 1.49 1.40 (m, 2H), 1.47 (s, 9H), 0.88 (t, J = 7.4 Hz, 3H) for E-4c; δ 7.22 (t, J = 8.0 Hz, 1H), 6.99 6.66 (m, 3H), 6.08 (t, J = 7.7 S19

Hz, 1H), 3.80 (s, 3H), 2.35 (dd, J = 14.9, 7.5 Hz, 2H), 1.56 1.51 (m, 2H), 1.55 (s, 9H), 0.98 (t, J = 7.4 Hz, 3H) for Z-4c; 13 C NMR (100 MHz, CDCl3) δ 167.76, 166.25, 160.51, 160.13, 143.52, 139.64, 137.83, 136.17, 135.75, 135.39, 107.83, 104.80, 99.57, 99.17, 81.37, 80.46, 55.20, 55.18, 31.80, 31.43, 28.13, 28.04, 22.45, 22.13, 13.82, 13.78 for Z, E mixture of 4c; HRMS (ESI) calcd for C17H24O3 m/z [M+H] + : 277.1804; found: 277.1792. tert-butyl 2-(3-methoxyphenyl)hept-2-enoate (4d): 1 H NMR (400 MHz, CDCl3) δ 7.25 (t, J = 7.9 Hz, 1H), 6.92 (t, J = 7.7 Hz, 1H), 6.86 6.81 (m, 1H), 6.77 6.72 (m, 1H), 6.70 (dd, J = 2.5, 1.5 Hz, 1H), 3.80 (s, 3H), 2.07 (dd, J = 14.9, 7.5 Hz, 2H), 1.46 (s, 9H), 1.44 1.23 (m, 4H), 0.84 (t, J = 7.2 Hz, 3H) for E-4d; δ 7.22 (t, J = 8.0 Hz, 1H), 6.96 6.79 (m, 3H), 6.07 (t, J = 7.7 Hz, 1H), 3.80 (s, 3H), 2.37 (dd, J = 14.8, 7.5 Hz, 2H), 1.55 (s, 9H), 1.52 1.21 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H) for Z-4d; 13 C NMR (100 MHz, CDCl3) δ 167.88, 166.45, 159.44, 159.04, 143.82, 139.21, 137.28, 136.32, 135.92, 135.16, 129.17, 128.69, 122.26, 119.19, 115.42, 112.92, 112.54, 112.29, 81.42, 80.51, 55.17, 55.15, 31.43, 31.07, 29.61, 29.21, 28.21, 28.09, 22.43, 22.37, 13.91, 13.83 for Z, E mixture of 4d; HRMS (ESI) calcd for C18H26O3 m/z [M+H] + : 291.1960; found: 291.1949. tert-butyl 2-(3-methoxyphenyl)oct-2-enoate (4e): 1 H NMR (400 MHz, CDCl3) δ 7.25 (dd, J = 9.5, 6.3 Hz, 1H), 6.92 (t, J = 7.7 Hz, 1H), 6.83 (ddd, J = 8.3, 2.6, 0.8 Hz, 1H), 6.74 (dd, J = 7.5, 0.9 Hz, 1H), 6.70 (dd, J = 2.4, 1.5 Hz, 1H), 3.80 (s, 3H), 2.06 (dd, J = 15.1, 7.6 Hz, 2H), 1.46 (s, 9H), 1.44 1.36 (m, 2H), 1.29 1.16 (m, 4H), 0.85 (t, J = 6.9 Hz, 3H) for E-4e; 13 C NMR (100 MHz, CDCl3) δ 166.43, 159.00, 143.86, 137.25, 135.10, 128.67, 122.22, 115.35, 112.53, 80.49, 55.11, 31.44, 29.44, 28.58, 28.06, 22.38, 13.89 for E-4e; HRMS (ESI) calcd for C19H28O3 m/z [M+H] + : 305.2117; found: 305.2135. tert-butyl 2-(3-methoxyphenyl)-4-methylpent-2-enoate (4f): 1 H NMR (400 MHz, CDCl3) δ 7.28 7.21 (m, 2H), 6.97 6.89 (m, 2H), 6.86 6.78 (m, 2H), 6.78 6.68 (m, 3H), 5.86 (d, J = 10.0 Hz, 1H), 3.80 (s, 6H), 2.95 2.80 (m, 1H), 2.51 2.32 (m, 1H), 1.56 (s, 9H), 1.47 (s, 9H), 1.11 (d, J = 6.6 Hz, 6H), 1.00 (d, J = 6.6 Hz, 6H) for E : Z = 1:1 mixture of 4f; 13 C NMR (100 MHz, CDCl3) δ 167.87, 166.52, 159.40, 158.98, 149.78, 142.30, 138.93, 137.43, 133.77, 133.03, 129.12, 128.65, 121.97, 119.06, 115.23, S20

112.87, 112.37, 112.17, 81.36, 80.43, 55.05, 55.00, 29.25, 28.41, 28.11, 27.99, 22.63, 22.22 for E : Z = 1:1 mixture of 4f; HRMS (ESI) calcd for C17H24O3 m/z [M+H] + : 277.1804; found: 277.1802. tert-butyl 2-(3-methoxyphenyl)-5-methylhex-2-enoate (4g): 1 H NMR (400 MHz, CDCl3) δ 7.25 (t, J = 8.0 Hz, 1H), 6.95 (t, J = 7.6 Hz, 1H), 6.86 6.81 (m, 1H), 6.76 6.71 (m, 1H), 6.70 (dd, J = 2.4, 1.5 Hz, 1H), 3.80 (s, 3H), 2.01 1.93 (m, 2H), 1.77 1.70 (m, 1H), 1.46 (s, 9H), 0.88 (d, J = 6.7 Hz, 6H) for E-4g; δ 7.23 (t, J = 8.0 Hz, 1H), 6.98 6.79 (m, 3H), 6.09 (t, J = 7.7 Hz, 1H), 3.80 (s, 3H), 2.31 2.22 (m, 2H), 1.85 1.76 (m, 1H), 1.55 (s, 9H), 0.97 (d, J = 6.7 Hz, 6H) for Z-4g; 13 C NMR (100 MHz, CDCl3) δ 167.85, 166.37, 159.41, 158.98, 142.69, 139.20, 137.33, 136.51, 135.73, 134.91, 129.15, 128.64, 122.25, 119.12, 115.41, 112.84, 112.45, 112.27, 81.35, 80.44, 55.10, 55.08, 38.71, 38.31, 28.72, 28.35, 28.16, 28.04, 22.43 for Z, E mixture of 4g; HRMS (ESI) calcd for C18H26O3 m/z [M+H] + : 291.1960; found: 291.1940. tert-butyl 2-(3-methoxyphenyl)tetradec-2-enoate (4h): 1 H NMR (400 MHz, CDCl3) δ 7.25 (t, J = 7.9 Hz, 1H), 6.92 (t, J = 7.7 Hz, 1H), 6.83 (ddd, J = 8.3, 2.6, 0.8 Hz, 1H), 6.74 (dd, J = 7.5, 0.9 Hz, 1H), 6.71 (dd, J = 2.3, 1.5 Hz, 1H), 3.80 (s, 3H), 2.07 (dd, J = 15.0, 7.6 Hz, 2H), 1.47 (s, 9H), 1.43 1.14 (m, 18H), 0.88 (t, J = 6.9 Hz, 3H) for E-4h; 13 C NMR (100 MHz, CDCl3) δ 166.41, 159.01, 143.84, 137.25, 135.11, 128.65, 122.22, 115.37, 112.52, 80.46, 55.08, 31.86, 29.62, 29.58, 29.57, 29.46, 29.36, 29.34, 29.29, 29.26, 28.89, 28.18, 28.06, 22.64, 14.06 for E-4h; HRMS (ESI) calcd for C25H40O3 m/z [M+H] + : 389.3056; found: 389.3040. tert-butyl 5-(benzyloxy)-2-(3-methoxyphenyl)pent-2-enoate (4i): 1 H NMR (400 MHz, CDCl3) δ7.39 7.20 (m, 6H), 6.99 (t, J = 7.5 Hz, 1H), 6.97 6.72 (m, 3H), 4.49 (s, 2H), 3.78 (s, 3H), 3.54 (t, J = 6.6 Hz, 2H), 2.42 (dd, J = 14.0, 6.6 Hz, 2H), 1.49 (s, 9H) for E- 4i; δ 7.39 7.20 (m, 6H), 6.97 6.72 (m, 3H) 6.18 (t, J = 7.4 Hz, 1H), 4.55 (s, 2H), 3.81 (s, 3H), 3.63 (t, J = 6.6 Hz, 2H), 2.73 (q, J = 6.7 Hz, 2H), 1.54 (s, 9H) for Z-4i; 13 C NMR (100 MHz, CDCl3) δ 167.48, 166.10, 159.39, 159.07, 139.74, 139.06, 138.30, 138.21, 137.36, 136.86, 136.78, 132.92, 129.14, 128.78, 128.35, 128.33, 127.67, 127.56, 122.15, S21

119.38, 115.30, 113.14, 112.82, 112.43, 81.62, 80.68, 72.89, 72.82, 69.28, 68.75, 55.15, 55.10, 30.47, 30.17, 28.17, 28.06 for Z, E mixture of 4i; HRMS (ESI) calcd for C23H28O4 m/z [M+H] + : 369.2066; found: 369.2048. tert-butyl 2-(3-methoxyphenyl)hepta-2,6-dienoate (4j): 1 H NMR (400 MHz, CDCl3) δ 7.26 (t, J = 7.9 Hz, 1H), 6.99 6.67 (m, 4H), 5.94 5.66 (m, 1H), 5.15 4.88 (m, 2H), 3.80 (s, 3H), 2.29 2.24 (m, 2H), 2.26 2.09 (m, 2H), 1.47 (s, 9H) for E-4j; δ 7.23 (t, J = 7.9 Hz, 1H), 6.99 6.67 (m, 3H), 6.08 (t, J = 7.6 Hz, 1H), 5.94 5.66 (m, 1H), 5.15 4.88 (m, 2H), 3.80 (s, 3H), 2.48 (q, J = 7.4 Hz, 2H), 2.26 2.09 (m, 2H); 1.55 (s, 9H) for Z-4j; 13 C NMR (100 MHz, CDCl3) δ 167.69, 166.28, 159.40, 159.04, 142.62, 139.07, 137.63, 137.35, 137.07, 136.31, 135.58, 135.41, 129.17, 128.74, 122.15, 119.24, 115.32, 115.28, 115.20, 112.96, 112.63, 112.37, 81.53, 80.59, 55.13, 55.12, 33.26, 32.87, 29.11, 28.81, 28.18, 28.05 for Z, E mixture of 4j; HRMS (ESI) calcd for C18H24O3 m/z [M+H] + : 289.1804; found: 289.1803. tert-butyl 2-(benzo[d][1,3]dioxol-5-yl)hex-2-enoate (4k): 1 H NMR (400 MHz, CDCl3) δ 6.85 (d, J = 1.6 Hz, 1H), 6.80 (dd, J = 8.1, 1.6 Hz, 1H), 6.75 (d, J = 8.1 Hz, 1H), 5.96 (t, J = 7.7 Hz, 1H), 5.94 (s, 2H), 2.31 (q, J = 7.5 Hz, 2H), 1.54 (s, 9H), 1.52 1.47 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H) for Z-4k; 13 C NMR (100 MHz, CDCl3) δ 168.00, 147.54, 146.95, 135.75, 135.02, 132.12, 120.39, 108.04, 107.22, 101.02, 81.47, 31.86, 28.22, 22.59, 13.84 for Z-4k; HRMS (ESI) calcd for C17H22O4 m/z [M+H] + : 291.1596; found: 291.1582. tert-butyl 2-(3,5-dimethoxyphenyl)hex-2-enoate (4l): 1 H NMR (400 MHz, CDCl3) δ 6.89 (t, J = 7.7 Hz, 1H), 6.40 (t, J = 2.3 Hz, 1H), 6.31 (d, J = 2.3 Hz, 2H), 3.77 (s, 6H), 2.05 (dd, J = 15.0, 7.5 Hz, 2H), 1.46 (s, 9H), 1.45 1.39 (m, 2H), 0.88 (t, J = 7.4 Hz, 3H) for E-4l; δ 6.51 (d, J = 2.3 Hz, 2H), 6.38 (t, J = 2.2 Hz, 1H), 6.06 (t, J = 7.7 Hz, 1H), 3.77 (s, 6H), 2.32 (dd, J = 14.9, 7.5 Hz, 2H), 1.54 (s, 9H), 1.54 1.48 (m, 2H), 0.97 (t, J = 7.4 Hz, 3H) for Z-4l; 13 C NMR (100 MHz, CDCl3) δ 167.76, 166.25, 160.51, 160.13, 143.52, 139.64, 137.83, 136.17, 135.75, 135.39, 107.83, 104.80, 99.57, 99.17, 81.37, 80.46, 55.20, 55.18, 31.80, 31.43, 28.13, 28.04, 22.45, 22.13, 13.82, 13.78 for Z, E mixture of 4l; HRMS (ESI) calcd for C18H26O4 m/z [M+H] + : 307.1909; found: 307.1920. S22

tert-butyl 2-(thiophen-2-yl)hept-2-enoate (4m): 1 H NMR (400 MHz, CDCl3) δ 7.33 (dd, J = 5.1, 1.1 Hz, 1H), 7.01 (dd, J = 5.1, 3.5 Hz, 1H), 6.98 (t, J = 7.6 Hz, 1H), 6.94 (dd, J = 3.5, 1.1 Hz, 1H), 2.28 (dd, J = 14.9, 7.5 Hz, 2H), 1.50 (s, 9H), 1.48 1.26 (m, 4H), 0.88 (t, J = 7.2 Hz, 3H) for E-4m; 13 C NMR (100 MHz, CDCl3) δ 165.96, 145.55, 136.02, 128.29, 127.88, 126.05, 125.95, 81.11, 31.15, 29.59, 28.05, 22.41, 13.82 for E- 4m; HRMS (ESI) calcd for C15H22O2S m/z [M+H] + : 267.1419; found: 267.1432. tert-butyl 2-(furan-2-yl)hept-2-enoate (4n): 1 H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 1.1 Hz, 1H), 6.85 (t, J = 7.6 Hz, 1H), 6.50 (d, J = 3.3 Hz, 1H), 6.43 6.34 (m, 1H), 2.48 2.36 (m, 2H), 1.51 (s, 9H), 1.49 1.33 (m, 4H), 0.96 0.87 (m, 3H) for E-4n; 13 C NMR (100 MHz, CDCl3) δ 165.43, 149.37, 144.96, 141.71, 125.06, 110.78, 110.59, 80.98, 31.15, 29.35, 28.08, 22.46, 13.84 for E-4n; HRMS (ESI) calcd for C15H22O3 m/z [M+H] + : 251.1647; found: 251.1651. tert-butyl (E)-3-methoxy-2-phenylacrylate (E-4o): 1 H NMR (400 MHz, CDCl3) δ 7.44 (s, 1H), 7.33 (d, J = 4.3 Hz, 4H), 7.27 7.21 (m, 1H), 3.83 (s, 3H), 1.49 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 166.90, 158.68, 132.95, 130.21, 127.59, 126.86, 113.11, 80.30, 61.77, 28.27; HRMS (ESI) calcd for C14H18O3 m/z [M+H] + : 235.1334; found: 235.1320. tert-butyl (E)-3-methoxy-2-(3-methoxyphenyl)acrylate (E-4p): 1 H NMR (400 MHz, CDCl3) δ 7.44 (s, 1H), 7.25 (dd, J = 9.6, 6.3 Hz, 1H), 6.92 (ddd, J = 7.2, 3.1, 1.3 Hz, 2H), 6.80 (ddd, J = 8.3, 2.6, 0.8 Hz, 1H), 3.83 (s, 3H), 3.80 (s, 3H), 1.49 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 166.75, 158.87, 158.77, 134.20, 128.47, 122.73, 115.99, 112.94, 112.42, 80.29, 61.79, 55.11, 28.25; HRMS (ESI) calcd for C15H20O4 m/z [M+H] + : 239.1283; found: 265.1423. S23

tert-butyl (Z)-3-methoxy-2-(3-methoxyphenyl)acrylate (Z-4p): 1 H NMR (400 MHz, CDCl3) δ 7.20 (t, J = 7.9 Hz, 1H), 6.88 6.81 (m, 2H), 6.81 6.75 (m, 1H), 6.59 (s, 1H), 3.87 (s, 3H), 3.80 (s, 3H), 1.49 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 165.23, 159.19, 156.59, 137.32, 128.86, 121.03, 114.28, 114.05, 112.16, 80.69, 62.04, 55.12, 28.20; HRMS (ESI) calcd for C15H20O4 m/z [M+H] + : 265.1440; found: 265.1457. tert-butyl (E)-2-(3,5-dimethoxyphenyl)-3-methoxyacrylate (E-4q): 1 H NMR (400 MHz, CDCl3) δ 7.42 (s, 1H), 6.51 (d, J = 2.3 Hz, 2H), 6.38 (t, J = 2.3 Hz, 1H), 3.81 (s, 3H), 3.77 (s, 6H), 1.49 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 166.47, 159.83, 158.72, 134.58, 112.84, 108.30, 99.11, 80.10, 61.67, 55.03, 28.11; HRMS (ESI) calcd for C16H22O5 m/z [M+H] + : 295.1545; found: 295.1549. General Methods for Asymmetric Permanganate Oxidation: Method A: 0.025 mmol scale for optimization of dihydroxylation reaction condition. A 4 ml vial was charged with bisguanidium catalyst (0.5 umol, 2 mol%) and tert-butyl - phenylacrylate 1a (5.0 mg, 0.025 mmol) and 0.5 ml solvent. The resulting mixture was then cooled to -60 o C. Deionized water or aqueous salt solutions (0.05 ml) was added dropwise to the stirred mixture, during which icy particles were formed. (We found that this protocol provide the best results. The reproducibility of this protocol is quite good. All other methods follow this protocol with aqueous additive added under cryogenic condition dropwise.) Potassium permanganate (5.9 mg, 0.0375 mmol) was then added to the reaction in one batch. After completion, the reaction was diluted with ether and allowed to warm to room temperature. The organic layer was dried through a pipette column of anhydrous Na2SO4 and then concentrated, followed by column chromatography on silica gel with a pipette affording pure diol product for HPLC analysis. Method B: 0.2 mmol scale for extension of dihydroxylation substrate scope. A 8 ml vial was charged with bisguanidinium catalyst BG-IV (5.6 mg, 0.004 mmol, 2 mol%) and tert-butyl -arylacrylate 1 (0.2 mmol) and 4 ml TBME. The resulting mixture was then cooled to -60 o C. Aqueous 20 wt% KI (0.2 ml) was added dropwise to the stirred mixture, during which icy particles were formed. Potassium permanganate (47.4 mg, 0.3 mmol) was then added to the reaction in one batch. After completion, the reaction was diluted with ether and quenched with saturated Na2S2O3 (1 ml) and allowed to warm to room S24

temperature. The organic layer was dried through a column of anhydrous Na2SO4 with the aqueous layer extracted with ether and dried. The organic layer was combined and concentrated and then columned on silica gel, affording pure chiral diol products. Method C: 0.05 mmol scale for optimization of reaction condition with enoates 4a. A 4 ml vial was charged with bisguanidinium catalyst (1.4 mg, 0.001 mmol) and tert-butyl 2- (3-methoxyphenyl)but-2-enoate (4a, E : Z = 1.3 : 1) (10 mg, 0.05 mmol) and 1 ml TBME. Acetic acid (10 ul) was added if needed. The resulting mixture was then cooled to -60 o C. Deionized water or aqueous solutions (0.05 ml) was added dropwise to the stirred mixture, during which icy particles were formed. Potassium permanganate (11.8 mg, 0.075 mmol) was then added to the reaction in one batch. After reaction for 48 hours, the reaction was diluted with ether and quenched with saturated Na2S2O3 (0.5 ml) and allowed to warm to room temperature. The organic layer was dried through a column of anhydrous Na2SO4 with the aqueous layer extracted with ether and dried. The organic layer was combined and concentrated for 1 H NMR analysis. The crude product was then columned on silica gel, affording oxidized products for HPLC analysis. Method D: 0.2 mmol scale for extension of oxohydroxylation substrate scope. A 8 ml vial was charged with bisguanidinium catalyst BG-III (5.6 mg, 0.004 mmol, 2 mol%) and tert-butyl enoate 4 (0.2 mmol), acetic acid (40 ul) and 4 ml TBME. The resulting mixture was then cooled to -60 o C. Deionized water (0.2 ml) was added dropwise to the stirred mixture, during which icy particles were formed. Potassium permanganate (47.4 mg, 0.3 mmol) was then added to the reaction in one batch. After completion of the reaction, the reaction was diluted with ether and quenched with saturated Na2S2O3 (1 ml) and allowed to warm to room temperature. The organic layer was passed through a column of silica gel covered with anhydrous Na2SO4 with the aqueous layer extracted with ether. The organic layer was combined and concentrated and then columned on silica gel, affording oxohydroxylated products. Method E: 4 mmol scale reaction of tert-butyl 2-(3-methoxyphenyl)but-2-enoate (4a). A 250 ml round-bottom flask was charged with bisguanidium catalyst BG-III (56 mg, 0.04 mmol, 1 mol%) and tert-butyl enoate 4a (1.0g, 4 mmol), acetic acid (800 ul) and 80 ml TBME. The resulting mixture was then cooled to -60 o C. Deionized water (4 ml) was added dropwise to the stirred mixture, during which icy particles were formed. Potassium permanganate (948 mg, 6 mmol) was then added to the reaction in one batch. After reaction for 72 hours, the reaction was diluted with ether and quenched with saturated Na2S2O3 and allowed to warm to room temperature. The organic layer was separated and the aqueous layer was extracted with ether. The combined organic layer was passed through a column of silica gel covered with anhydrous Na2SO4. The organic layer was then concentrated and columned on silica gel, affording oxohydroxylated products 6a in 81% yield and 92% ee. S25

Reduction of Oxohydroxylated Product 6a Reduction of (R)-tert-butyl 2-hydroxy-2-(3-methoxyphenyl)-3-oxobutanoate (6a) with sodium borohydride: To a stirred solution of (R)-tert-butyl 2-hydroxy-2-(3- methoxyphenyl)-3-oxobutanoate 6a (76.5 mg, 0.273 mmol) in ethanol (2.7 ml) was added sodium borohydride (6.2 mg, 0.164 mmol, 0.6 eq) at 0 o C. After 30 min, TLC indicated full conversion of the starting material. Water was added at 0 o C to quench the reaction followed by addition of ethyl acetate. The organic layer was separated and aqueous layer was extracted with ethyl acetate. The combined organic layer was concentrated for 1 H NMR analysis, which indicated a ratio of 5a/5a = 1:1.07. The crude product was then purified by column chromatography on silica gel with hexane/ethyl acetate (5:1), affording diol 5a (94% ee) and 5a (88% ee) in 93% combined yield (71.7 mg). Excessive sodium borohydride will lead to a decreased yield. Reduction of (R)-tert-butyl 2-hydroxy-2-(3-methoxyphenyl)-3-oxobutanoate (6a) with sodium borohydride and zinc chloride 7 : An oven-dried round-bottom flask was charged with anhydrous zinc chloride (68 mg, 0.5 mmol) and sodium borohydride (19 mg, 0.5 mmol) and dry THF (3 ml) and protected with nitrogen. To the stirred mixture was added with (R)-tert-butyl 2-hydroxy-2-(3-methoxyphenyl)-3-oxobutanoate 6a (114 mg, 0.41 mmol) in dry THF (1 ml) at 0 o C. After full conversion of the starting material checked by TLC, water was added at 0 o C to quench the reaction followed by addition of ethyl acetate. The organic layer was separated and aqueous layer was extracted with ethyl acetate. The combined orgaic layer was concentrated for 1 H NMR analysis, which indicated a ratio of 5a/5a = 10:1. The crude product was then purified by column chromatography on silica gel with hexane/ethyl acetate (5:1), affording diol 5a (94% ee) and 5a (91% ee) in 92% combined yield (105.8 mg). S26

Characterization of Asymmetric Permanganate Dihydroxylation Products tert-butyl (R)-2,3-dihydroxy-2-phenylpropanoate (2a): 65% yield; colourless oil; 1 H NMR (400 MHz, CDCl3) δ 7.66 7.52 (m, 2H), 7.44 7.27 (m, 3H), 4.19 (d, J = 11.3 Hz, 1H), 3.72 (d, J = 11.3 Hz, 1H), 3.09 (br, 2H), 1.49 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 172.82, 138.63, 128.28, 128.04, 125.42, 83.89, 79.43, 68.32, 27.80; IR: 3479, 2980, 2930, 1717, 1369, 1275, 1159, 737 cm -1 ; HRMS (ESI) calcd for C13H18O4 m/z [M+H] + : 239.1283; found: 239.1286; [a] D 22 = +31.1 (c 1.5, ethyl acetate); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 ml/min, 230 nm, 22 C), 9.2, 11.3 (major) min, 92% ee. tert-butyl (R)-2,3-dihydroxy-2-(p-tolyl)propanoate (2b): 62% yield; colourless oil; 1 H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 4.16 (d, J = 11.3 Hz, 1H), 3.69 (d, J = 11.3 Hz, 1H), 2.34 (s, 3H), 1.49 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 172.97, 137.76, 135.71, 128.98, 125.32, 83.74, 79.33, 68.35, 27.81, 20.99; IR: 3478, 2980, 2928, 1715, 1512, 1369, 1159, 739 cm -1 ; HRMS (ESI) calcd for C14H20O4 m/z [M+H] + : 253.1440; found: 253.1445; [a] D 22 = +34.8 (c 1.4, ethyl acetate); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 ml/min, 230 nm, 22 C), 9.5, 10.7 (major) min, 90% ee. tert-butyl (R)-2,3-dihydroxy-2-(m-tolyl)propanoate (2c): 72% yield; colourless oil; 1 H NMR (400 MHz, CDCl3) δ 7.42 (s, 1H), 7.37 (d, J = 7.9 Hz, 1H), 7.24 (t, J = 7.9 Hz, 1H), 7.12 (d, J = 7.5 Hz, 1H), 4.18 (d, J = 11.3 Hz, 1H), 3.71 (d, J = 11.3 Hz, 1H), 2.36 (s, 3H), 1.49 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 172.88, 138.56, 137.91, 128.75, 128.13, 126.08, 122.46, 83.75, 79.44, 68.32, 27.80, 21.53; IR: 3468, 2978, 2930, 1719, 1369, 1271, 1155, 737 cm -1 ; HRMS (ESI) calcd for C14H20O4 m/z [M+H] + : 253.1440; found: 253.1444; [a] D 22 = +29.8 (c 1.8, ethyl acetate); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 ml/min, 230 nm, 22 C), 8.7, 10.5 (major) min, 85% ee. S27

tert-butyl (R)-2-(4-ethylphenyl)-2,3-dihydroxypropanoate (2d): 67% yield; colourless oil; 1 H NMR (400 MHz, CDCl3) δ 7.54 7.44 (m, 2H), 7.19 (d, J = 8.4 Hz, 2H), 4.16 (d, J = 11.3 Hz, 1H), 3.70 (d, J = 11.3 Hz, 1H), 3.13 (br, 2H), 2.64 (d, J = 7.6 Hz, 2H), 1.50 (s, 9H), 1.23 (t, J = 7.6 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 172.97, 144.04, 135.90, 127.76, 125.38, 83.73, 79.38, 68.39, 28.37, 27.82, 15.32; IR: 3478, 2968, 2932, 1720, 1369, 1267, 1159, 739 cm -1 ; HRMS (ESI) calcd for C15H22O4 m/z [M+H] + : 267.1596; found: 267.1600; [a] D 22 = +28.9 (c 1.8, ethyl acetate); HPLC analysis: Chiralcel OJ-H (Hex/IPA = 98/2, 1.0 ml/min, 230 nm, 22 C), 9.2 (major), 20.3 min, 89% ee. tert-butyl (R)-2-([1,1'-biphenyl]-4-yl)-2,3-dihydroxypropanoate (2e): 64% yield; white solid; mp: 84.1-85.0 C; 1 H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.3 Hz, 2H), 7.63 7.55 (m, 4H), 7.45 (dd, J = 8.2, 6.9 Hz, 2H), 7.36 (t, J = 7.3 Hz, 1H), 4.23 (d, J = 11.3 Hz, 1H), 3.77 (d, J = 11.3 Hz, 1H), 3.22 (br, 2H), 1.53 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 172.77, 140.87, 140.46, 137.62, 128.75, 127.40, 127.03, 126.98, 125.92, 83.97, 79.39, 68.39, 27.83; IR: 3466, 2978, 2930, 1715, 1369, 1265, 1157, 737 cm -1 ; HRMS (ESI) calcd for C19H22O4 m/z [M+H] + : 315.1596; found: 315.1597; [a] D 22 = +25.5 (c 2.0, ethyl acetate); HPLC analysis: Chiralcel OJ-H (Hex/IPA = 90/10, 1.0 ml/min, 230 nm, 22 C), 13.2 (major), 15.8 min, 90% ee. tert-butyl (R)-2,3-dihydroxy-2-(4-methoxyphenyl)propanoate (2f): 71% yield; colourless oil; 1 H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 9.0 Hz, 2H), 6.87 (d, J = 9.0 Hz, 2H), 4.14 (d, J = 11.3 Hz, 1H), 3.79 (s, 3H), 3.68 (d, J = 11.3 Hz, 1H), 3.14 (br, 2H), 1.48 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 173.03, 159.30, 130.73, 126.68, 113.60, 83.69, 79.10, 68.33, 55.18, 27.80; IR: 3480, 2978, 2934, 1720, 1510, 1252, 1159, 739 cm - 1 ; HRMS (ESI) calcd for C14H20O5 m/z [M+H] + : 269.1389; found: 269.1397; [a] D 22 = +30.0 (c 1.9, ethyl acetate); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 ml/min, 230 nm, 22 C), 13.6, 15.2 (major) min, 86% ee. S28

tert-butyl (R)-2,3-dihydroxy-2-(3-methoxyphenyl)propanoate (2g): 65% yield; colourless oil; 1 H NMR (400 MHz, CDCl3) δ 7.26 (t, J = 7.9 Hz, 1H), 7.16 (t, J = 5.2 Hz, 2H), 6.90 6.79 (m, 1H), 4.16 (d, J = 11.4 Hz, 1H), 3.80 (s, 3H), 3.69 (d, J = 11.4 Hz, 1H), 2.43 (br, 1H), 1.49 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 172.69, 159.55, 140.24, 129.25, 117.75, 113.55, 111.22, 83.89, 79.43, 68.37, 55.16, 27.81; IR: 3462, 2978, 2934, 1719, 1601, 1256, 1155, 737 cm -1 ; HRMS (ESI) calcd for C14H20O5 m/z [M+H] + : 269.1389; found: 269.1385; [a] D 22 = +31.8 (c 1.6, ethyl acetate); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 ml/min, 230 nm, 22 C), 12.8, 15.1 (major) min, 96% ee. tert-butyl (R)-2,3-dihydroxy-2-(4-(methylthio)phenyl)propanoate (2h): 65% yield; colourless solid; mp: 84.9-85.6 C; 1 H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 8.7 Hz, 2H), 7.22 (d, J = 8.6 Hz, 2H), 4.14 (d, J = 11.3 Hz, 1H), 3.68 (d, J = 11.3 Hz, 1H), 3.18 (br, 2H), 2.47 (s, 3H), 1.48 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 172.70, 138.46, 135.37, 126.12, 125.95, 83.92, 79.16, 68.27, 27.79, 15.50; IR: 3443, 2980, 2924, 1715, 1597, 1265, 1157, 737 cm -1 ; HRMS (ESI) calcd for C14H20O4S m/z [M+H] + : 285.1161; found: 285.1164; [a] D 22 = +29.3 (c 1.9, ethyl acetate); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 ml/min, 230 nm, 22 C), 13.8, 14.8 (major) min, 84% ee. tert-butyl (R)-2-(3,4-dimethylphenyl)-2,3-dihydroxypropanoate (2i): 63% yield; colourless solid; mp: 59.7-60.5 C; 1 H NMR (400 MHz, CDCl3) δ 7.36 (s, 1H), 7.29 (dd, J = 7.9, 1.8 Hz, 1H), 7.11 (d, J = 7.9 Hz, 1H), 4.16 (d, J = 11.3 Hz, 1H), 3.70 (d, J = 11.3 Hz, 1H), 3.08 (br, 2H), 2.27 (s, 3H), 2.25 (s, 3H), 1.50 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 173.02, 136.47, 136.41, 136.08, 129.53, 126.58, 122.79, 83.65, 79.32, 68.39, 27.83, 19.93, 19.34; IR: 3466, 2978, 2930, 1718, 1369, 1267, 1157, 739 cm -1 ; HRMS (ESI) calcd for C15H22O4 m/z [M+H] + : 267.1596; found: 267.1601; [a] 22 D = +29.7 (c 1.7, ethyl acetate); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 ml/min, 230 nm, 22 C), 8.2, 9.7 (major) min, 86% ee. tert-butyl (R)-2-(benzo[d][1,3]dioxol-5-yl)-2,3-dihydroxypropanoate (2j): 60% yield; colourless oil; 1 H NMR (400 MHz, CDCl3) δ 7.11 7.02 (m, 2H), 6.78 (d, J = 8.1 Hz, 1H), 5.95 (s, 2H), 4.10 (d, J = 11.3 Hz, 1H), 3.66 (d, J = 11.3 Hz, 1H), 1.49 (s, 9H); 13 C S29

NMR (100 MHz, CDCl3) δ 172.79, 147.67, 147.32, 132.58, 118.93, 107.97, 106.29, 101.12, 83.93, 79.17, 68.39, 27.81; IR: 3468, 2980, 2930, 1718, 1489, 1244, 1039, 739 cm -1 ; HRMS (ESI) calcd for C14H18O6 m/z [M+H] + : 283.1182; found: 283.1181; [a] D 22 = +29.6 (c 1.4, ethyl acetate); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 ml/min, 230 nm, 22 C), 15.8, 20.1 (major) min, 92% ee. tert-butyl (R)-2-(3,5-dimethoxyphenyl)-2,3-dihydroxypropanoate (2k): 63% yield; colourless oil; 1 H NMR (400 MHz, CDCl3) δ 6.76 (d, J = 2.3 Hz, 2H), 6.40 (t, J = 2.2 Hz, 1H), 4.12 (d, J = 11.4 Hz, 1H), 3.78 (s, 6H), 3.68 (d, J = 11.4 Hz, 1H), 2.45 (br, 1H), 1.50 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 172.57, 160.64, 141.01, 103.65, 100.06, 83.88, 79.53, 68.39, 55.26, 27.82; IR: 3478, 2978, 2936, 1715, 1599, 1155, 1065, 841, 739 cm -1 ; HRMS (ESI) calcd for C15H22O6 m/z [M+H] + : 299.1495; found: 299.1494; [a] D 22 = +31.3 (c 1.9, ethyl acetate); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 ml/min, 230 nm, 22 C), 15.5, 17.1 (major) min, 94% ee. tert-butyl (2R,3S)-2,3-dihydroxy-2-(3-methoxyphenyl)butanoate (5a): colourless oil; 1 H NMR (400 MHz, CDCl3) δ 7.25 (t, J = 7.9 Hz, 1H), 7.22 7.15 (m, 2H), 6.83 (ddd, J = 8.0, 2.5, 0.9 Hz, 1H), 4.45 (q, J = 6.4 Hz, 1H), 4.02 (br, 1H), 3.81 (s, 3H), 1.99 (br, 1H), 1.49 (s, 9H), 0.96 (d, J = 6.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 173.45, 159.52, 140.78, 129.13, 117.99, 113.17, 111.34, 83.80, 81.16, 72.32, 55.17, 27.80, 16.97; IR: 3470, 2978, 2934, 1715, 1601, 1371, 1258, 1146, 737 cm -1 ; HRMS (ESI) calcd for C15H22O5 m/z [M+H] + : 283.1545; found: 283.1547; [a] D 22 = +28.9 (c 2.0, ethyl acetate); HPLC analysis: Chiralcel AD-H (Hex/IPA = 90/10, 1.0 ml/min, 230 nm, 22 C), 13.7, 17.2 (major) min, 92% ee. tert-butyl (2R,3R)-2,3-dihydroxy-2-(3-methoxyphenyl)butanoate (5a ): colourless solid; mp: 54.4-55.0 C; 1 H NMR (400 MHz, CDCl3) δ 7.32 7.22 (m, 3H), 6.87 6.82 (m, 1H), 4.38 (q, J = 6.3 Hz, 1H), 3.81 (s, 3H), 1.83 (br, 1H), 1.47 (s, 9H), 1.25 (d, J = 6.3 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 172.44, 159.56, 141.07, 129.18, 118.43, 113.50, 111.92, 84.03, 80.49, 71.97, 55.17, 27.79, 17.20; IR: 3485, 2978, 2936, 1715, 1601, 1371, 1258, 1142, 737 cm -1 ; HRMS (ESI) calcd for C15H22O5 m/z [M+H] + : S30