Supporting information for: Domino Synthesis of Functionalized Cyclic Acetals from Organic Carbonates

Page S1 Supporting information for: Domino Synthesis of Functionalized Cyclic Acetals from Organic Carbonates Natalia Kulbacka, Wangyu Shi, Sophie M. Guillaume, JeanFrançois Carpentier, Jordi Benet-Buchholz and Arjan W. Kleij* N. Kulbacka, W. Shi, J. Benet-Buchholz, A. W. Kleij Institute of Chemical Research of Catalonia (ICIQ-CERCA), the Barcelona Institute of Science & Technology (BIST), 43007 - Tarragona, Spain E-mail: aklei[email protected]s N. Kulbacka, W. Shi Departament de Química Física i Inorgànica, Universitat Rovira i Virgili, Tarragona, Spain S. M. Guillaume, J.-F. Carpentier Univ. Rennes, CNRS, Institut des Sciences Chimiques de Rennes, UMR 6226, Rennes, France Arjan W. Kleij Catalan Institute of Research and Advanced Studies (ICREA), Pg. Lluis Companys 23, 08010 – Barcelona, Spain * Correspondence e-mail: [email protected] Page S2 Table of Contents 1. General remarks ............................................................................................. 3 2. Procedures for the synthesis of 6-membered cyclic carbonates .................... 4 3. Procedures for the synthesis of 5-membered cyclic carbonates .................... 6 4. Experimental procedures for the preparation of cyclic acetals ....................... 9 5. Optimization of the reaction conditions ......................................................... 10 6. Identification and isolation of byproducts ...................................................... 11 7. Transformations of cyclic acetals ................................................................. 14 8. Deuteration-labeling experiments ................................................................. 20 9. Characterization data for all new compounds ............................................... 21 10. Copies of 1H NMR, 13C NMR and IR spectra .............................................. 43 11. X-ray molecular structures ........................................................................ 149 12. References ............................................................................................... 153 Page S3 1. General remarks All reagents and solvents were used as received from commercial suppliers (SigmaAldrich, Fluorochem, Apollo or TCI) unless stated otherwise. Carbon dioxide was purchased from PRAXAIR and used without further purification. Reactions were monitored by TLC and/or 1H NMR. TLC was carried out on 0.25 mm Merck aluminum backed sheets coated with 60 F254 silica gel. Visualization of the silica plates was achieved using a UV lamp (  = 254 nm) and/or by using the stain solutions of KMnO4 or cerium ammonium molybdate. Flash column chromatography was carried out on SigmaAldrich silica gel 60 (70-230 mesh) using the indicated eluents. Heating was achieved in an oil bath on a magnetic stirring plate using an IKA RCT basic magnetic stirring hotplate. All reactions were mixed with magnetic stirrers. 1H, 13C and 2D NMR spectra were recorded at room temperature on Bruker AV-300, AV400 or AV-500 spectrometers in CDCl3. The residual solvent signals were used as references for 1H and 13C NMR spectra (CDCl3: δH = 7.26 ppm, δC = 77.16 ppm). Coupling constants (J) are reported in Hertz (Hz) with the following splitting abbreviations: s = singlet, bs = broad singlet, d = doublet, t = triplet, q = quadruplet, p = quintet, h = sextet, hept = heptet and m = multiplet. FT-IR measurements were carried out on a Bruker Optics FTIR-ATR TR0 spectrometer. High Resolution Mass Spectrometry (HRMS) data were obtained from the Research Support Area (RSA) at ICIQ and collected on a MicroTOF II (Bruker Daltonics). X-ray diffraction studies were performed by the Research Support Area (RSA) at ICIQ. Solvents were dried using an Innovative Technology PURE SOLV solvent purification system. Page S4 2. Procedures for the synthesis of 6-membered cyclic carbonates Compounds 1a-1e, 1g and 1i-1k were directly prepared following the General Method. Compounds 1f and 1h were prepared following Method A. All epoxides and known compounds (cyclic carbonates) were synthesized according to previously reported procedures.1 General Method: In a typical experiment, 0.30 mmol of epoxide 1A, alkynyl electrophile 1B (50.4 mg, 0.6 mmol, 2 equiv) and AltBu (4.5 mg, 0.006 mmol, 2 mol%) were added in a 30 mL stainless steel reactor. Then, premixed N-methyl-morpholine (6.0 mg, 0.06 mmol, 20 mol%) and 200 μL toluene were added through a syringe. The reactor was purged twice with CO2 (10 bar) and then charged with CO2 to 10 bar. The mixture was stirred at 75 °C for 22 h, then cooled with an ice/water bath and carefully depressurized. The solvent was removed in vacuo and the resulting product was purified by flash chromatography employing hexane and ethyl acetate (abbreviated further as EA) with a 3:1 to 2:1 v/v gradient as eluent. Page S5 Method A: The starting cyclic carbonates were either used as received from commercial suppliers or prepared according to previously reported procedures.1 To 1 mmol of cyclic carbonate in 1.0 mL toluene, the corresponding alkynyl electrophile (168.2 mg, 2 mmol, 2 equiv) and N-methyl-morpholine (20.2 mg, 0.2 mmol, 20 mol%) were added. The mixture was stirred at 50 °C for 22 h, then the solvent was removed in vacuo and the resulting product was purified by flash chromatography employing hexane and EA (3:1 to 2:1 gradient) as eluent. Page S6 3. Procedures for the synthesis of 5-membered cyclic carbonates Compounds 3a-3j and 3r were directly prepared following the General Method. Compounds 3o-3p were prepared following Method A and compound 3k was prepared following Method B. NOTE: To achieve full conversion of the starting cyclic carbonate, for compounds 3a-3c the reactions were conducted in 1.11 mL of acetonitrile. For compounds 3l-3n the reactions were conducted in 1.11 mL of toluene at 75 ºC, using 20 mol% of N-methyl-Nphenyl-2-propynamide as a base. General Method: The starting cyclic carbonates were used as received from commercial suppliers or prepared according to previously reported procedures utilizing catalyst AlCl.2 To 1 mmol of cyclic carbonate in 2 mL acetonitrile, the corresponding alkynyl electrophile (168.2 mg, 2 mmol, 2 equiv) and 1,4diazabicyclo[2.2.2]octane (11.2 mg, 0.10 mmol, 10 mol%) were added. The mixture was stirred at room temperature for 22 h, then the solvent was removed in vacuo and the resulting product was purified by flash chromatography employing hexane and EA (2:1 v/v) as eluent. Page S7 Method A: To commercially available glycerol-1,2-carbonate (1 mmol) in 5 mL tetrahydrofuran, the corresponding alkynyl electrophile was added: in the case of 3o this was tosyl-acetylene (270.3 mg, 1.5 mmol, 1.5 equiv). Next, 1,4-diazabicyclo[2.2.2]octane (11.2 mg, 0.10 mmol, 10 mol%) was added and the mixture was stirred at room temperature for 5-20 minutes. Then, the solvent was removed in vacuo and the resulting product was purified by flash chromatography employing pure EA as eluent. NOTE: The N-methyl-N-phenyl-2-propynamide used for the preparation of 3p was synthesized according to a previously reported procedure.1 Page S8 Method B: In a typical experiment, 0.30 mmol of epoxide, alkynyl electrophile (50.4 mg, 0.60 mmol, 2 equiv) and AltBu (4.5 mg, 0.006 mmol, 2 mol%) were added in a 30 mL stainless steel reactor. Then, premixed N-methyl-morpholine (6.0 mg, 0.06 mmol, 20 mol%) and 200 μL toluene were added through a syringe. The reactor was purged twice with CO2 (10 bar) and then charged with CO2 to 10 bar. The mixture was stirred at 75 °C for 22 h, then cooled with an ice/water bath and carefully depressurized. The solvent was removed in vacuo and the resulting product 3k was purified by flash chromatography employing hexane and EA (3:1 v/v) as eluent. Page S9 4. Experimental procedures for the preparation of cyclic acetals Compounds 2a-2c, 2e-2g, 2i-2k, 4h-4j and 4n were directly prepared following the General Method. Compounds 2d, 2h, 4a-4g, 4k-4m and 4o-4p were prepared following Method A. General Method: In a typical procedure, to a stirred solution of the cyclic carbonate (0.20 mmol, 1 equiv) in 1.0 mL of solvent (THF:MeOH = 4:1 v/v), NaBH4 (8.32 mg, 0.22 mmol, 1.1 equiv) was added at 0 oC. After stirring the reaction mixture for 24 h at r.t., it was quenched by water, extracted with EtOAc (2  5 mL) and dried over Na2SO4 following filtration. The organic phase was concentrated to dryness and the residue was purified by flash chromatography employing hexane and EA (3:1 v/v) as eluent. Where applicable, crystals suitable for X-ray diffraction were produced from a mixture of CH2Cl2, EtOAc and hexane. Method A: To a stirred solution of the cyclic carbonate (0.20 mmol, 1 equiv) in 1.0 mL of solvent (THF:MeOH = 4:1 v/v), NaBH4 (11.4 mg, 0.30 mmol, 1.5 equiv) was added at 0 oC. After stirring the reaction mixture for 24 h at r.t., it was quenched by water, extracted with EtOAc (2  5 mL) and dried over Na2SO4 (note: smaller amount than used in the General Method) following filtration. The organic phase was concentrated to dryness and the residue was purified by flash chromatography employing hexane and EA (3:1 v/v) as eluent. Where applicable, crystals suitable for X-ray diffraction were produced from a mixture of CH2Cl2, EtOAc and hexane. Page S16 Oxa-Michael addition reaction involving the free alcohol group. To a vial equipped with a magnetic stirring bar, compound 4a (25.2 mg, 0.10 mmol, 1 equiv) and dry MeCN (0.3 mL) were charged. To this solution methyl propiolate (16.8 mg, 0.2 mmol, 2 equiv) was added, followed by addition of DABCO (1.12 mg, 10.0 mol, 10 mol%). The reaction mixture was stirred at room temperature for 22 h and then complete conversion was determined by TLC. The mixture was concentrated to dryness and the residue was purified by flash chromatography employing hexane and EA (3:1 v/v) as eluent to obtain methyl 8 as a colorless oil in 78% yield (25.4 mg, 0.0783 mmol) with a dr > 20:1. Data for 8: 1H NMR (500 MHz, CDCl3) δ 7.40 – 7.34 (m, 4H), 7.32 – 7.29 (m, 2H), 5.54 (t, J = 4.9 Hz, 1H), 5.24 (d, J = 7.3 Hz, 1H), 4.96 (d, J = 12.5 Hz, 1H), 4.58 – 4.52 (m, 1H), 3.77 (s, 3H), 3.67 (s, 3H), 3.49 – 3.44 (m, 1H), 3.38 (dd, J = 10.9, 4.0 Hz, 1H), 3.01 – 2.92 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 169.46, 167.79, 161.83, 135.38, 128.69, 128.58, 126.45, 101.04, 96.69, 79.54, 70.40, 52.03, 51.13, 39.33; IR (neat, C=O, cm-1): ν = 1706, 1737; HRMS (ESI+; MeOH): m/z calcd. (C17H20NaO7) 359.1101 (M+Na)+: found: 359.1092. Page S17 Cross-coupling involving the bromo-aryl group. In a nitrogen-filled vial, 4c (30 mg, 0.091 mmol, 1 equiv), PdCl2(PPh3)2 (3.2 mg, 4.53 mol, 5 mol%) and K2CO3 (25.0 mg, 0.181 mmol, 2 equiv) were charged. The vial was evacuated and refilled back three times with nitrogen. Then dry 1,4-dioxane (1.2 mL) was added, the mixture was then bubbled through with a stream of nitrogen for 5 min. Then PhPpin (27.7 mg, 0.136 mmol, 1.50 equiv) was added and the reaction mixture was heated to 80 ºC and stirred for 22 h at this temperature. Hereafter, the crude was quenched by the addition of water and EA, the phases were separated and the aqueous phase was extracted two times with EA. The combined organic phases were washed with brine, dried over Na2SO4, concentrated to dryness and the residue was purified by flash chromatography employing hexane/EA (3:1 v/v) as eluent. The 1H NMR spectrum of the product still showed the presence of starting material 4c, and therefore the crude was resubjected to the same experimental conditions as described above. The product was isolated in the same way, giving finally product 9, 2-(4-([1,1'-biphenyl]-4-yl)-5-(hydroxymethyl)-1,3dioxolan-2-yl)acetate, as a colorless oil in 60 % yield (17.8 mg, 0.069 mmol) and with a dr > 20:1. Data for 9: 1H NMR (500 MHz, CDCl3) δ 7.64 – 7.59 (m, 4H), 7.49 – 7.44 (m, 2H), 7.42 – 7.36 (m, 3H), 5.55 (t, J = 4.9 Hz, 1H), 5.25 (d, J = 7.3 Hz, 1H), 4.46 – 4.43 (m, 1H), 3.79 (s, 3H), 3.35 – 3.24 (m, 2H), 3.04 – 2.93 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 169.68, 141.24, 140.49, 134.76, 128.84, 127.51, 127.16, 127.08, 126.89, 100.68, 79.75, 79.48, 62.55, 52.05, 39.57: IR (neat, C=O, cm-1): ν = 1737; HRMS (ESI+; MeOH): m/z calcd. (C19H20NaO5) 351.1203 (M+Na)+: found: 351.1186. Page S18 Nucleophilic substitution of the primary alcohol. To a nitrogen-filled vial was charged compound 4a (33.0 mg, 0.131 mmol, 1 equiv) and the vial was evacuated and refilled back three times with nitrogen. Then, dry DCM (1.2 mL) was added followed by the addition of 1-chloro-4-isocyanatobenzene (24.1 mg, 0.157 mmol ,1.2 equiv) and Et3N (1.32 mg, 13.1 mol, 10 mol %). The reaction mixture was stirred at room temperature for 3 h. After this time, the crude was quenched with water, the phases were separated and the aqueous phase was extracted two times with DCM (15 mL), dried over Na2SO4, concentrated to dryness and the residue was purified by flash chromatography employing hexane and EA (4:1 v/v) as eluent to obtain 10 as a white solid in 85 % yield (45.0 mg, 0.11 mmol) with a dr > 20:1. Data for 10: 1H NMR (500 MHz, CDCl3) δ 7.39 – 7.32 (m, 5H), 7.26 (s, 4H), 6.66 (s, 1H), 5.55 (t, J = 5.1 Hz, 1H), 5.24 (d, J = 7.3 Hz, 1H), 4.57 – 4.52 (m, 1H), 3.87 (dd, J = 11.9, 3.5 Hz, 1H), 3.77 (s, 3H), 2.99 (d, J = 5.1 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 169.74, 152.74, 136.29, 135.50, 133.48, 130.10, 129.02, 128.59, 128.57, 126.46, 119.81, 100.94, 79.47, 64.74, 52.06, 39.50; IR (neat, C=O, cm-1): ν = 1731; HRMS (ESI+; MeOH): m/z calcd. (C20H20ClNNaO6) 428.0871 (M+Na)+: found: 428.0877. Page S19 LiOH-induced ester hydrolysis To a vial equipped with a magnetic stirring bar, compound 4a (43.3 mg, 0.172 mmol, 1 equiv) and THF (1 mL) were charged. The solution was stirred until 4a had dissolved and then water was added to obtain a 3:1 v/v mixture of THF/H2O. To this solution, LiOH·H2O (21.6 mg, 0.515 mmol, 3 equiv) was added and the reaction mixture was stirred at room temperature for another 20 h. After this time, THF was removed from the reaction mixture by evaporation and the mixture was diluted with water (3 mL) followed by adjusting the pH to 3 with aqueous 1.0 M HCl. Then, the mixture was extracted two times with EtOAc and washed with brine, followed by drying the combined organic phases over Na2SO4 and concentration to dryness to provide 11 as a colorless oil in 89% yield (36.3 mg, 0.152 mmol) with a dr > 20:1. Data for 11: 1H NMR (500 MHz, CDCl3) δ 7.40 – 7.34 (m, 3H), 7.34 – 7.31 (m, 2H), 5.53 (t, J = 4.9 Hz, 1H), 5.22 (d, J = 7.3 Hz, 1H), 4.45 – 4.40 (m, 1H), 3.29 – 3.18 (m, 2H), 3.05 – 2.94 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 173.68, 135.52, 128.52, 126.34, 125.86, 100.36, 79.66, 79.63, 62.51, 39.40; IR (neat, C=O, cm-1): ν = 1718; HRMS (ESI+; MeOH): m/z calcd. (C12H14NaO5) 261.0733 (M+Na)+: found: 261.0745. Page S20 8. Deuteration-labeling experiments To a stirred solution of a cyclic carbonate 1a (0.20 mmol, 1 equiv) in 1.0 mL of solvent (THF:CD3OD = 4:1 v/v), NaBH4 was added [for (a), 11.4 mg, 0.30 mmol, 1.5 equiv] or NaBD4 [for (b), 12.6 mg, 0.30 mmol, 1.5 equiv] at 0 oC. After stirring the reaction mixture for 24 h at r.t., it was quenched by water, extracted with EtOAc (2  5 mL) and dried over Na2SO4 following filtration. The organic phase was concentrated to dryness and the residue was purified by flash chromatography employing hexane and EA (2:1 v/v) as eluent to provide [under (a)] 14 as a colorless oil in 48% yield (33.5mg, 0.9670 mmol) with a dr of 3:1, and under (b) 15 a colorless oil in 66% yield (46.0 mg, 0.133 mmol) with a dr of 3:1. The percentage of deuteration for 14 was calculated to be 43% and for 15 53%, and these calculations were based on comparative signal integrations with their nonlabeled compounds. Page S21 9. Characterization data for all new compounds Five-membered cyclic carbonates Data for 3a: The product was isolated as a yellow solid, eluent 33% EA in hexane. Yield: 96%, 302.1 mg. 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 12.5 Hz, 1H), 7.49 – 7.39 (m, 3H), 7.33 – 7.29 (m, 2H), 5.30 (d, J = 12.5 Hz, 1H), 5.25 (d, J = 3.7 Hz, 1H), 4.93 – 4.87 (m, 1H), 4.60 – 4.54 (m, 1H), 4.38 (t, J = 8.7 Hz, 1H), 3.67 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 167.24, 159.84, 154.20, 132.88, 129.69, 129.51, 126.17, 100.44, 81.50, 77.38, 64.44, 51.31; IR (neat, C=O, cm-1): ν = 1799, 1706; HRMS (ESI+; MeOH): m/z calcd. (C14H14NaO6) 301.0683 (M+Na)+: found: 301.0693. Data for 3b: The product was isolated as a colorless oil, eluent 25% to 33% EA in hexane. Yield: 90%, 579.6 mg. 1H NMR (400 MHz, CDCl3) δ 7.49 – 7.41 (m, 4H), 7.32 – 7.29 (m, 2H), 5.23 – 5.18 (m, 2H), 4.92 – 4.86 (m, 1H), 4.57 (dd, J = 8.8, 5.8 Hz, 1H), 4.38 – 4.32 (m, 1H), 1.45 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 166.21, 159.03, 154.34, 133.09, 129.54, 129.43, 126.20, 125.73, 102.23, 81.19, 80.23, 77.45, 64.51, 28.18; IR (neat, C=O, cm-1): ν = 1807, 1700; HRMS (ESI+; MeOH): m/z calcd. (C17H20NaO6) 343.1152 (M+Na)+: found: 343.1155. Page S22 Data for 3c: The product was isolated as a colorless oil, eluent 33% EA in hexane. Yield: 85%, 110.6 mg. 1H NMR (400 MHz, CDCl3) δ 7.63 – 7.58 (m, 2H), 7.49 (d, J = 12.6 Hz, 1H), 7.23 – 7.18 (m, 2H), 5.29 (d, J = 12.6 Hz, 1H), 5.18 (d, J = 4.1 Hz, 1H), 4.89 – 4.83 (m, 1H), 4.55 – 4.49 (m, 1H), 4.41 (t, J = 8.7 Hz, 1H), 3.68 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 166.99, 159.38, 153.88, 132.77, 132.03, 127.85, 124.03, 100.81, 81.02, 64.58, 51.39, 29.70; IR (neat, C=O, cm-1): ν = 1807, 1710; HRMS (ESI+; MeOH): m/z calcd. (C14H13BrNaO6) 378.9788 (M+Na)+: found: 378.9786. Data for 3d: The product was isolated as a colorless oil, eluent 33% EA in hexane. Yield: 99%, 161.9 mg. 1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 12.5 Hz, 1H), 7.46 – 7.43 (m, 2H), 7.28 – 7.24 (m, 2H), 5.29 (d, J = 12.5 Hz, 1H), 5.19 (d, J = 4.1 Hz, 1H), 4.90 – 4.83 (m, 1H), 4.55 – 4.49 (m, 1H), 4.42 (t, J = 8.6 Hz, 1H), 3.68 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 167.01, 159.41, 153.90, 135.88, 131.51, 129.81, 127.61, 100.78, 82.80, 80.98, 64.60, 51.38, 30.92; IR (neat, C=O, cm-1): ν = 1800, 1704; HRMS (ESI+; MeOH): m/z calcd. (C14H13ClNaO6) 335.0293 (M+Na)+: found: 335.0283. Page S23 Data for 3e: The product was isolated as a colorless oil, eluent 33% EA in hexane. Yield: 84%, 139.8 mg. 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 12.5 Hz, 1H), 7.22 – 7.18 (m, 2H), 5.18 (d, J = 12.6 Hz, 1H), 5.14 (d, J = 4.2 Hz, 1H), 4.86 – 4.81 (m, 1H), 4.53 – 4.49 (m, 1H), 4.41 – 4.35 (m, 1H), 1.45 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 165.94, 158.51, 153.98, 132.72, 132.23, 127.85, 123.88, 102.64, 80.65, 80.49, 64.63, 28.18; IR (neat, C=O, cm-1): ν = 1806, 1698; HRMS (ESI+; MeOH): m/z calcd. (C17H19BrNaO6) 421.0257 (M+Na)+: found: 421.0261. Data for 3f: The product was isolated as a colorless oil, eluent 33% EA in hexane. Yield: 66%, 125.3 mg. 1H NMR (400 MHz, CDCl3) δ 7.47 – 7.43 (m, 2H), 7.40 (d, J = 12.5 Hz, 1H), 7.28 – 7.24 (m, 2H), 5.20 – 5.14 (m, 2H), 4.87 – 4.81 (m, 1H), 4.54 – 4.49 (m, 1H), 4.41 (t, J = 8.6 Hz, 1H), 1.45 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 165.96, 158.52, 153.98, 135.76, 131.70, 129.78, 127.59, 102.64, 80.62, 80.49, 64.64, 28.18; IR (neat, C=O, cm-1): ν = 1810, 1700; HRMS (ESI+; MeOH): m/z calcd. (C17H19ClNaO6) 377.0762 (M+Na)+: found: 377.0766. Page S24 Data for 3g: The product was isolated as a colorless oil, eluent 50% EA in hexane. Yield: 80%, 237.06 mg. 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 12.6 Hz, 1H), 7.43 – 7.28 (m, 5H), 5.28 (d, J = 12.6 Hz, 1H), 4.61 (s, 2H), 4.39 (d, J = 1.4 Hz, 2H), 4.08 – 3.97 (m, 2H), 3.74 (s, 3H), 3.66 (d, J = 1.8 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 167.29, 160.93, 153.69, 136.55, 128.70, 128.37, 127.92, 98.16, 81.83, 73.95, 70.24, 69.57, 68.13, 51.37; IR (neat, C=O, cm-1): ν = 1800, 1705; HRMS (ESI+; MeOH): m/z calcd. (C16H18NaO7) 345.0945 (M+Na)+: found: 345.0940. Data for 3h: The product was isolated as a light-yellow oil, eluent 50% to 100% EA in hexane. Yield: 80%, 161.7 mg. 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 12.6 Hz, 1H), 5.30 (d, J = 12.6 Hz, 1H), 4.98 (ddt, J = 8.5, 6.0, 3.7 Hz, 1H), 4.60 (t, J = 8.6 Hz, 1H), 4.42 (dd, J = 8.7, 6.0 Hz, 1H), 4.14 (dd, J = 11.3, 3.6 Hz, 1H), 4.02 (dd, J = 11.3, 3.7 Hz, 1H), 3.73 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 167.27, 160.85, 154.15, 98.17, 73.41, 69.02, 65.68, 51.40; IR (neat, C=O, cm-1): ν = 1779, 1739; HRMS (ESI+; MeOH): m/z calcd. (C8H10NaO6) 225.0370 (M+Na)+: found: 225.0391. *Note that cyclic acetal product 4i was obtained using carbonate 3h and allylic alcohol, causing in situ trans-esterification. Page S25 Data for 3j: The product was isolated as a colorless oil, eluent 50% EA in hexane. Yield: 82%, 200.3 mg. 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 12.6 Hz, 1H), 5.21 (d, J = 12.6 Hz, 1H), 4.97 (m, 1H), 4.60 (t, J = 8.6 Hz, 1H), 4.41 (dd, J = 8.6, 5.9 Hz, 1H), 4.10 (dd, J = 11.3, 3.8 Hz, 1H), 3.98 (dd, J = 11.3, 3.7 Hz, 1H), 1.49 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 166.17, 159.94, 154.24, 100.04, 80.34, 73.45, 68.70, 65.74, 28.23; IR (neat, C=O, cm-1): ν = 1789; HRMS (ESI+; MeOH): m/z calcd. (C11H16NaO6) 267.0839 (M+Na)+: found: 267.0832. Data for 3k: The product was isolated as a colorless oil, eluent 33% EA in hexane. Yield: 82%, 290.6 mg. 1H NMR (400 MHz, CDCl3) δ 7.50 – 7.42 (m, 5H), 7.41 – 7.34 (m, 4H), 7.28 – 7.21 (m, 2H), 5.57 (dd, J = 6.0, 4.4 Hz, 1H), 5.01 (d, J = 12.6 Hz, 1H), 3.78 – 3.70 (m, 2H), 3.69 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 167.26, 160.66, 152.83, 139.68, 136.52, 129.42, 129.19, 129.05, 128.79, 126.09, 125.90, 97.73, 88.61, 80.89, 68.97, 51.29; IR (neat, C=O, cm-1): ν = 1809; HRMS (ESI+; MeOH): m/z calcd. (C20H18NaO6) 377.0996 (M+Na)+: found: 377.1008. Page S32 Data for 2g: The product was isolated as a colorless oil, eluent 33% to 50% EA in hexane. Yield: 69%, 33.7 mg (2:1 dr). 1H NMR (400 MHz, CDCl3) δ 5.44 (t, J = 5.3 Hz, 1H), 5.33 (t, J = 5.1 Hz, 1H), 4.45 – 4.32 (m, 2H), 4.23 (dd, J = 8.3, 6.0 Hz, 1H), 4.06 (dd, J = 7.8, 6.4 Hz, 1H), 3.73 (s, 5H), 3.62 – 3.57 (m, 1H), 3.53 (dd, J = 8.2, 7.3 Hz, 1H), 2.74 (dd, J = 5.2, 1.0 Hz, 2H), 2.70 (dd, J = 5.3, 0.8 Hz, 1H), 2.02 (m, 2H), 1.90 – 1.70 (m, 9H), 1.69 – 1.56 (m, 7H); 13C NMR (101 MHz, CDCl3) δ 169.75, 169.71, 101.08, 100.30, 81.28, 81.21, 75.39, 74.51, 71.32, 70.56, 51.89, 43.72, 43.08, 40.32, 40.07, 39.91, 39.73, 39.69, 23.56, 23.52, 23.49; IR (neat, C=O, cm-1): ν = 1737; HRMS (ESI+; MeOH): m/z calcd. (C12H20NaO5) 267.1203 (M+Na)+: found: 267.1212. Data for 2h: The product was isolated as a colorless oil, eluent 33% EA in hexane. Yield: 36%, 9.3 mg (2:1 dr). 1H NMR (400 MHz, CDCl3) δ 5.32 (t, J = 5.2 Hz, 1H), 4.47 – 4.34 (m, 2H), 4.22 (dd, J = 8.2, 6.0 Hz, 1H), 4.05 (dd, J = 7.8, 6.5 Hz, 1H), 3.72 (s, 5H), 3.57 (dd, J = 7.8, 7.0 Hz, 1H), 2.73 (dd, J = 5.1, 2.2 Hz, 2H), 2.70 (d, J = 5.3 Hz, 1H), 1.87 – 1.78 (m, 2H), 1.74 (d, J = 4.4 Hz, 1H), 1.72 – 1.58 (m, 9H), 1.57 – 1.39 (m, 8H), 1.36 – 1.26 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 169.78, 101.04, 100.29, 73.91, 72.94, 71.42, 70.86, 70.77, 70.63, 51.90, 40.06, 39.92, 38.44, 38.38, 37.51, 37.49, 25.76, 25.74, 22.23, 22.20, 22.11; IR (neat, C=O, cm-1): ν = 1737; HRMS (ESI+; MeOH): m/z calcd. (C13H22NaO5) 281.1359 (M+Na)+: found: 281.1372. Page S33 Data for 2i: The product was isolated as a colorless oil, eluent 25% to 33% EA in hexane. Yield: 49%, 26.8 mg (2:1 dr). 1H NMR (400 MHz, CDCl3) δ 5.44 (t, J = 5.3 Hz, 1H), 5.32 (t, J = 5.2 Hz, 2H), 4.46 – 4.32 (m, 3H), 4.22 (dd, J = 8.2, 6.0 Hz, 1H), 4.05 (dd, J = 7.8, 6.5 Hz, 2H), 3.72 (d, J = 0.6 Hz, 8H), 3.58 (dd, J = 7.8, 6.9 Hz, 2H), 3.51 (dd, J = 8.3, 7.4 Hz, 1H), 2.74 (dd, J = 5.2, 1.5 Hz, 3H), 2.70 (d, J = 5.3 Hz, 2H), 2.63 (s, 1H), 2.45 (s, 2H), 1.86 – 1.76 (m, 7H), 1.74 – 1.67 (m, 12H), 1.66 – 1.54 (m, 12H), 1.49 – 1.41 (m, 5H), 1.34 – 1.26 (m, 3H); 13C NMR (101 MHz, CDCl3) δ 169.74, 169.68, 101.08, 100.32, 74.98, 74.89, 74.36, 73.41, 71.46, 70.67, 51.89, 45.46, 44.81, 41.87, 41.82, 41.10, 40.05, 39.91, 29.93, 29.90, 29.87, 22.37, 22.35, 22.13; IR (neat, C=O, cm-1): ν = 1738; HRMS (ESI+; MeOH): m/z calcd. (C14H24NaO5) 295.1516 (M+Na)+: found: 295.1523. Data for 2j: The product was isolated as a colorless oil, eluent 20% EA in hexane. Yield: 59%, 40.3 mg (3:1 dr). 1H NMR (400 MHz, CDCl3) δ 7.67 – 7.59 (m, 4H), 7.58 – 7.54 (m, 1H), 7.42 – 7.30 (m, 6H), 5.20 (t, J = 5.2 Hz, 1H), 3.99 (p, J = 6.6 Hz, 1H), 3.72 (s, 3H), 3.56 – 3.52 (m, 1H), 3.37 (dd, J = 8.1, 6.7 Hz, 1H), 2.95 (s, 1H), 2.70 (dd, J = 5.1, 0.7 Hz, 2H), 2.65 – 2.60 (m, 2H), 2.19 (dd, J = 13.8, 6.6 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 169.72, 169.68, 148.21, 147.98, 139.27, 139.10, 129.35, 129.33, 129.16, 129.14, 128.01, 127.99, 124.08, 123.82, 120.21, 120.20, 120.16, 120.14, 100.73, 100.41, 81.17, 81.13, 74.33, 73.45, 71.15, 70.18, 51.90, 43.28, 42.54, 39.97, 39.95; IR (neat, C=O, cm-1): ν = 1738; HRMS (ESI+; MeOH): m/z calcd. (C20H20NaO5) 363.1203 (M+Na)+: found: 363.1208. Page S34 Data for 2k: The product was isolated as a colorless oil, eluent 33% EA in hexane. Yield: 68%, 46.6 mg (2:1 dr). 1H NMR (400 MHz, CDCl3) δ 8.07 – 7.93 (m, 3H), 7.32 – 7.08 (m, 9H), 5.17 (t, J = 5.1 Hz, 1H), 3.85 (s, 1H), 3.84 – 3.77 (m, 2H), 3.74 (d, J = 5.3 Hz, 4H), 3.55 – 3.47 (m, 1H), 3.44 – 3.31 (m, 3H), 3.10 – 3.00 (m, 1H), 2.98 – 2.90 (m, 1H), 2.80 – 2.66 (m, 4H), 2.63 (d, J = 5.3 Hz, 1H), 2.44 – 2.36 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 169.61, 143.83, 138.63, 137.80, 130.82, 129.97, 127.69, 127.38, 127.17, 127.07, 126.61, 126.37, 100.89, 100.20, 77.98, 74.33, 70.13, 51.95, 48.09, 47.13, 39.98, 39.67, 34.63, 34.35; IR (neat, C=O, cm-1): ν = 1737; HRMS (ESI+; MeOH): m/z calcd. (C22H24NaO5) 391.1516 (M+Na)+: found: 391.1525. Data for 4a: The product was isolated as a white solid, eluent 25% to 33% EA in hexane. Yield: 65%, 32.9 mg (20:1 dr). 1H NMR (400 MHz, CDCl3) δ 7.41 – 7.30 (m, 5H), 5.53 (t, J = 5.0 Hz, 1H), 5.21 (d, J = 7.3 Hz, 1H), 4.44 – 4.37 (m, 1H), 3.78 (s, 3H), 3.28 – 3.15 (m, 2H), 2.96 (dd, J = 5.0, 3.5 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 169.70, 135.76, 128.45, 128.34, 126.40, 100.62, 79.73, 79.59, 62.51, 52.04, 39.56; IR (neat, C=O, cm-1): ν = 1735; HRMS (ESI+; MeOH): m/z calcd. (C13H16NaO5) 275.0890 (M+Na)+: found: 275.0890. Page S35 Data for 4b: The product was isolated as a white solid, eluent 33% EA in hexane. Yield: 76%, 44.8 mg (20:1 > dr). 1H NMR (400 MHz, CDCl3) δ 7.40 – 7.30 (m, 5H), 5.48 (t, J = 5.0 Hz, 1H), 5.20 (d, J = 7.2 Hz, 1H), 4.40 (d, J = 4.7 Hz, 1H), 3.27 – 3.16 (m, 2H), 2.85 (dd, J = 6.3, 5.0 Hz, 2H), 1.51 (s, 9H); 13C NMR (101 MHz, CDCl3) δ 168.60, 135.87, 128.41, 128.26, 126.38, 101.01, 81.44, 79.54, 77.22, 62.53, 40.93, 28.12; IR (neat, C=O, cm-1): ν = 1726; HRMS (ESI+; MeOH): m/z calcd. (C16H22NaO5) 317.1359 (M+Na)+: found: 317.1357. Data for 4c: The product was isolated as a colorless oil, eluent 50% EA in hexane. Yield: 42%, 27.6 mg (20:1 = dr). 1H NMR (400 MHz, CDCl3) δ 7.52 – 7.47 (m, 2H), 7.22 – 7.18 (m, 2H), 5.49 (t, J = 4.9 Hz, 1H), 5.15 (d, J = 7.3 Hz, 1H), 4.42 – 4.35 (m, 1H), 3.77 (s, 3H), 3.20 (d, J = 5.8 Hz, 2H), 2.94 (dd, J = 4.9, 1.5 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 169.56, 134.95, 131.57, 128.16, 122.27, 100.68, 79.55, 79.06, 62.33, 52.08, 39.35; IR (neat, C=O, cm-1): ν = 1737; HRMS (ESI+; MeOH): m/z calcd. (C13H15BrNaO5) 352.9995 (M+Na)+: found: 352.9995. Page S36 Data for 4d: The product was isolated as a colorless oil, eluent 50% EA in hexane. Yield: 47%, 26.7 mg (20:1 = dr). 1H NMR (400 MHz, CDCl3) δ 7.38 – 7.33 (m, 2H), 7.28 – 7.24 (m, 2H), 5.51 (t, J = 4.9 Hz, 1H), 5.18 (d, J = 7.3 Hz, 1H), 4.43 – 4.36 (m, 1H), 3.77 (s, 3H), 3.21 (d, J = 5.7 Hz, 2H), 2.95 (dd, J = 4.9, 1.3 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 169.56, 134.41, 134.15, 128.63, 127.84, 100.67, 79.61, 79.03, 62.34, 52.07, 39.36; IR (neat, C=O, cm-1): ν = 1737; HRMS (ESI+; MeOH): m/z calcd. (C13H15ClNaO5) 309.0500 (M+Na)+: found: 309.0504. Data for 4e: The product was isolated as a colorless oil, eluent 33% EA in hexane. Yield: 54%, 40.1 mg (20:1 > dr).1H NMR (400 MHz, CDCl3) δ 7.52 – 7.48 (m, 2H), 7.24 – 7.19 (m, 2H), 5.46 (s, 1H), 5.15 (d, J = 7.3 Hz, 1H), 4.41 – 4.35 (m, 1H), 3.21 (d, J = 5.7 Hz, 2H), 2.89 – 2.78 (m, 2H), 1.51 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 168.49, 135.14, 131.51, 128.17, 122.17, 101.05, 81.57, 79.45, 78.99, 62.33, 40.69, 28.12; IR (neat, C=O, cm-1): ν = 1730; HRMS (ESI+; MeOH): m/z calcd. (C16H21BrNaO5) 395.0465 (M+Na)+: found: 395.0458. Page S37 Data for 4f: The product was isolated as a colorless oil, eluent 33% EA in hexane. Yield: 72%, 47.2 mg (20:1 > dr). 1H NMR (400 MHz, CDCl3) δ 7.37 – 7.32 (m, 2H), 7.28 – 7.25 (m, 2H), 5.46 (t, 1H), 5.17 (d, J = 7.3 Hz, 1H), 4.41 – 4.35 (m, 1H), 3.21 (d, J = 5.7 Hz, 2H), 2.89 – 2.78 (m, 2H), 1.51 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 168.50, 134.59, 134.05, 128.58, 127.85, 101.04, 81.56, 79.50, 78.96, 62.34, 40.70, 28.12; IR (neat, C=O, cm-1): ν = 1729; HRMS (ESI+; MeOH): m/z calcd. (C16H21ClNaO5) 351.0970 (M+Na)+: found: 351.0959. Data for 4g: The product was isolated as a colorless oil, eluent 50% EA in hexane. Yield: 58%, 32.4 mg (1:1 dr). 1H NMR (400 MHz, CDCl3) δ 7.41 – 7.35 (m, 5H), 7.32 (d, J = 7.0 Hz, 7H), 5.42 (t, J = 5.1 Hz, 1H), 5.38 (t, J = 4.4 Hz, 1H), 4.63 – 4.51 (m, 5H), 4.08 (d, J = 8.7 Hz, 2H), 3.89 – 3.82 (m, 2H), 3.75 (s, 3H), 3.73 (s, 3H), 3.72 (s, 4H), 3.64 – 3.51 (m, 5H), 3.46 (d, J = 9.2 Hz, 1H), 2.77 (dd, J = 4.4, 1.4 Hz, 2H), 2.71 (d, J = 5.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 169.82, 169.75, 137.68, 128.49, 127.88, 127.68, 127.66, 101.51, 101.11, 82.90, 82.24, 73.69, 71.94, 71.00, 69.71, 69.52, 64.54, 64.01, 51.98, 51.90, 40.08, 38.97; IR (neat, C=O, cm-1): ν = 1736; HRMS (ESI+; MeOH): m/z calcd. (C15H20NaO6) 319.1152 (M+Na)+: found: 319.1166. Page S38 Data for 4h: The product was isolated as a colorless oil, eluent 50% EA in hexane. Yield: 60%, 52.9 mg (1:1 dr). 1H NMR (400 MHz, CDCl3) δ 5.46 (t, J = 5.2 Hz, 1H), 5.31 (t, J = 4.6 Hz, 1H), 4.31 – 4.23 (m, 2H), 4.16 – 4.11 (m, 1H), 3.96 (d, J = 6.4 Hz, 3H), 3.85 – 3.79 (m, 1H), 3.79 – 3.75 (m, 1H), 3.74 (s, 7H), 3.69 – 3.63 (m, 1H), 3.63 – 3.54 (m, 2H), 2.79 (d, J = 4.6 Hz, 2H), 2.71 (d, J = 5.2 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 169.88, 169.86, 101.22, 101.11, 76.47, 66.56, 66.38, 62.84, 62.40, 52.00, 51.94, 39.84, 39.03; IR (neat, C=O, cm-1): ν = 1733; HRMS (ESI+; MeOH): m/z calcd. (C7H12NaO5) 199.0577 (M+Na)+: found: 199.0581. Data for 4i: The product was isolated as a colorless oil, eluent 25% EA in hexane. Yield: 40%, 104 mg (1:1 dr). 1H NMR (500 MHz, CDCl3) δ 5.98 – 5.88 (m, 1H), 5.38 – 5.23 (m, 3H), 4.64 (dd, J = 5.8, 1.5 Hz, 2H), 4.30 – 4.22 (m, 1H), 3.96 – 3.92 (m, 1H), 3.84 – 3.71 (m, 2H), 3.59 (dd, J = 12.0, 4.4 Hz, 1H), 2.77 (dd, J = 34.1, 4.9 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 169.15, 169.10, 131.83, 131.77, 118.63, 118.51, 101.18, 101.12, 76.50, 66.55, 66.36, 65.56, 65.46, 62.81, 62.39, 39.95, 39.21; IR (neat, C=O, cm-1): ν = 1734; HRMS (ESI+; MeOH): m/z calcd. (C9H14NaO5) 225.0733 (M+Na)+: found: 225.0733. Page S39 Data for 4j: The product was isolated as a colorless oil, eluent 50% EA in hexane. Yield: 72%, 31.3 mg (1:1 dr). 1H NMR (500 MHz, CDCl3) δ 5.40 (t, J = 5.2 Hz, 1H), 5.26 (t, J = 4.6 Hz, 1H), 4.25 (m, 2H), 4.12 (dd, J = 8.3, 6.6 Hz, 1H), 3.96 (s, 1H), 3.94 (s, 1H), 3.81 (dt, J = 12.0, 3.7 Hz, 1H), 3.76 – 3.71 (m, 2H), 3.64 (dt, J = 11.5, 5.0 Hz, 1H), 3.58 (m, 1H), 2.67 (dd, J = 4.6, 1.0 Hz, 2H), 2.66 – 2.63 (m, 1H), 2.61 (d, J = 5.2 Hz, 2H), 2.33 (d, J = 6.2 Hz, 1H), 1.47 (s, 18H); 13C NMR (126 MHz, CDCl3) δ 168.89, 168.86, 101.46, 81.47, 81.26, 76.71, 76.38, 66.49, 66.30, 62.86, 62.44, 41.03, 40.31, 28.09, 28.07; IR (neat, C=O, cm-1): ν = 1726; HRMS (ESI+; MeOH): m/z calcd. (C10H18NaO5) 241.1046 (M+Na)+: found: 241.1049. Data for 4k: The product was isolated as a colorless oil, eluent 17% EA in hexane. Yield: 49%, 32.3 mg (3:1 dr). 1H NMR (400 MHz, CDCl3) δ 7.63 – 7.59 (m, 1H), 7.58 – 7.52 (m, 2H), 7.48 – 7.44 (m, 1H), 7.41 – 7.32 (m, 5H), 7.31 – 7.20 (m, 4H), 5.54 (t, J = 5.1 Hz, 1H), 5.09 (dd, J = 8.6, 6.3 Hz, 1H), 3.88 (t, J = 8.6 Hz, 1H), 3.72 (d, J = 9.6 Hz, 5H), 2.95 (s, 1H), 2.83 – 2.71 (m, 3H); 13C NMR (101 MHz, CDCl3) δ 169.84, 169.68, 145.85, 145.51, 143.42, 142.77, 128.34, 128.30, 128.28, 128.17, 127.49, 127.28, 127.16, 127.13, 127.09, 126.66, 125.54, 102.77, 101.57, 80.42, 79.25, 77.36, 77.10, 67.03, 66.19, 52.00, 51.90, 40.12, 37.91; IR (neat, C=O, cm-1): ν = 1737; HRMS (ESI+; MeOH): m/z calcd. (C19H20NaO5) 351.1203 (M+Na)+: found: 351.1216. Page S40 Data for 4l: The product was isolated as a white solid, eluent 25% to 33% EA in hexane. Yield: 80%, 54.8 mg (6:1 dr). 1H NMR (500 MHz, CDCl3) δ 7.48 – 7.41 (m, 4H), 7.33 – 7.25 (m, 6H), 7.21 – 7.15 (m, 1H), 5.22 (dd, J = 6.1, 4.8 Hz, 1H), 4.05 – 3.99 (m, 1H), 3.75 (s, 3H), 3.72 – 3.60 (m, 2H), 2.92 – 2.79 (m, 3H), 2.65 – 2.60 (m, 1H), 2.08 – 2.00 (m, 1H); 13C NMR (126 MHz, CDCl3) δ 169.89, 147.50, 141.55, 128.87, 128.40, 128.20, 128.18, 127.59, 127.50, 126.85, 126.12, 125.44, 124.73, 93.39, 89.99, 80.11, 73.91, 70.66, 65.60, 63.98, 51.87, 51.78, 40.79, 40.44, 35.93, 34.85; IR (neat, C=O, cm-1): ν = 1737; HRMS (ESI+; MeOH): m/z calcd. (C20H22NaO5) 365.1359 (M+Na)+: found: 365.1358. Data for 4m: The product was isolated as a white solid, eluent 17% to 67% EA in hexane. Yield: 54%, 23.9 mg (6:1 dr). 1H NMR (400 MHz, CDCl3) δ 7.49 – 7.31 (m, 8H), 7.26 – 7.14 (m, 2H), 5.19 –5.15 (m, 1H), 4.05 – 3.97 (m, 1H), 3.75 – 3.60 (m, 2H), 2.82 – 2.68 (m, 2H), 2.64 (dd, J = 14.0, 2.0 Hz, 1H), 2.08 – 1.98 (m, 2H), 1.51 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 168.73, 147.61, 141.69, 129.32, 128.87, 128.15, 127.49, 127.41, 126.76, 126.10, 125.49, 124.64, 93.74, 80.94, 79.88, 73.73, 65.67, 42.48, 35.88, 29.71, 28.13; IR (neat, C=O, cm-1): ν = 1728; HRMS (ESI+; MeOH): m/z calcd. (C23H28NaO5) 407.1829 (M+Na)+: found: 407.1838. Page S41 Data for 4n: The product was isolated as a colorless oil using as an eluent 25% to 33% EA in hexane. Yield: 45%, 37.6 mg (7:1 dr). 1H NMR (500 MHz, CDCl3) δ 7.33 – 7.28 (m, 3H), 7.23 – 7.17 (m, 4H), 7.09 – 7.05 (m, 2H), 5.23 – 5.19 (m, 1H), 4.04 – 3.98 (m, 1H), 3.74 (s, 3H), 3.72 – 3.68 (m, 1H), 3.65 – 3.60 (m, 1H), 2.91 – 2.78 (m, 3H), 2.57 (dd, J = 14.0, 2.0 Hz, 1H), 2.35 (d, J = 10.6 Hz, 3H), 2.30 (d, J = 8.4 Hz, 3H), 2.04 – 1.97 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 169.88, 144.93, 138.61, 137.17, 136.39, 129.53, 128.81, 127.37, 126.01, 125.31, 124.68, 93.30, 89.78, 79.97, 73.89, 70.76, 65.69, 63.92, 51.83, 51.73, 40.80, 40.40, 36.00, 21.04, 21.01, 20.96; IR (neat, C=O, cm-1): ν = 1740; HRMS (ESI+; MeOH): m/z calcd. (C22H26NaO5) 393.1672 (M+Na)+: found: 393.1672. Data for 4o: The product was isolated as a brown solid, eluent 100% EA. Yield: 55%, 29.8 mg (2:1 dr). 1H NMR (400 MHz, CDCl3) δ 7.86 – 7.80 (m, 3H), 7.40 – 7.36 (m, 3H), 5.36 (t, J = 4.6 Hz, 1H), 4.25 – 4.12 (m, 2H), 3.96 – 3.90 (m, 1H), 3.89 – 3.83 (m, 1H), 3.80 (dd, J = 12.2, 3.3 Hz, 1H), 3.74 – 3.68 (m, 1H), 3.62 – 3.57 (m, 1H), 3.54 (d, J = 4.4 Hz, 1H), 3.51 – 3.48 (m, 2H), 3.44 (d, J = 4.8 Hz, 1H), 2.48 (s, 5H); 13C NMR (101 MHz, CDCl3) δ 145.05, 136.92, 136.76, 129.99, 129.83, 128.23, 127.90, 99.19, 98.95, 66.44, 65.93, 62.20, 62.11, 59.85, 59.51, 21.67, 21.65; IR (neat, OH, cm-1): ν = 3498; HRMS (ESI+; MeOH): m/z calcd. (C12H16NaO5S) 295.0611 (M+Na)+: found: 295.0609. Page S48 IR spectrum (neat) of 3c. Page S49 1H NMR (3d, 400 MHz, CDCl3) 13C NMR (3d, 101 MHz, CDCl3) Page S50 IR spectrum (neat) of 3d. Page S51 1H NMR (3e, 400 MHz, CDCl3) 13C NMR (3e, 126 MHz, CDCl3) Page S52 IR spectrum (neat) of 3e. Page S53 1H NMR (3f, 400 MHz, CDCl3) 13C NMR (3f, 126 MHz, CDCl3) Page S54 IR spectrum (neat) of 3f. Page S55 1H NMR (3g, 400 MHz, CDCl3) 13C NMR (3g, 101 MHz, CDCl3) Page S56 IR spectrum (neat) of 3g. Page S57 1H NMR (3h, 400 MHz, CDCl3) 13C NMR (3h, 101MHz, CDCl3) Page S64 IR spectrum (neat) of 3l. Page S65 1H NMR (3m, 400 MHz, CDCl3) 13C NMR (3m, 126 MHz, CDCl3) Page S66 IR spectrum (neat) of 3m. Page S67 1H NMR (3n, 400MHz, CDCl3) 13C NMR (3n, 126 MHz, CDCl3) Page S68 IR spectrum (neat) of 3n. Page S69 1H NMR (3o, 400 MHz, CDCl3) 13C NMR (3o, 126 MHz, CDCl3) Page S70 IR spectrum (neat) of 3o. Page S71 1H NMR (3p, 400 MHz, CDCl3) 13C NMR (3p, 101 MHz, CDCl3) Page S72 IR spectrum (neat) of 3p. Page S73 1H NMR (3r, 400MHz, CDCl3) 13C NMR (3r, 126MHz, CDCl3) Page S80 IR spectrum (neat) of 2c. Page S81 1H NMR (2d, 500 MHz, CDCl3) 13C NMR (2d, 101 MHz, CDCl3) Page S82 IR spectrum (neat) of 2d. Page S83 1H NMR (2e, 500 MHz, CDCl3) 13C NMR (2e, 101 MHz, CDCl3) Page S84 IR spectrum (neat) of 2e. Page S85 1H NMR (2f, 400 MHz, CDCl3) 13C NMR (2f, 101 MHz, CDCl3) Page S86 IR spectrum (neat) of 2f. Page S87 1H NMR (2g, 400 MHz, CDCl3) 13C NMR (2g, 101 MHz, CDCl3) Page S88 IR spectrum (neat) of 2g. Page S89 1H NMR (2h, 400 MHz, CDCl3) 13C NMR (2h, 126 MHz, CDCl3) Page S96 IR spectrum (neat) of 2k. Page S97 1H NMR (4a, 400 MHz, CDCl3) 13C NMR (4a, 126 MHz, CDCl3) Page S98 IR spectrum (neat) of 4a. Page S99 1H NMR (4b, 400 MHz, CDCl3) 13C NMR (4b, 101 MHz, CDCl3) Page S100 IR spectrum (neat) of 4b. Page S101 1H NMR (4c, 400 MHz, CDCl3) 13C NMR (4c, 126 MHz, CDCl3) Page S102 IR spectrum (neat) of 4c. Page S103 1H NMR (4d, 400 MHz, CDCl3) 13C NMR (4d, 126 MHz, CDCl3) Page S104 IR spectrum (neat) of 4d. Page S105 1H NMR (4e, 400 MHz, CDCl3) 13C NMR (4e, 126 MHz, CDCl3) Page S112 IR spectrum (neat) of 4h. Page S113 1H NMR (4i, 500 MHz, CDCl3) 13C NMR (4i, 126 MHz, CDCl3) Page S114 IR spectrum (neat) of 4i. Page S115 1H NMR (4j, 500 MHz, CDCl3) 13C NMR (4j, 126 MHz, CDCl3) Page S116 IR spectrum (neat) of 4j. Page S117 1H NMR (4k, 400 MHz, CDCl3) 13C NMR (4k, 101 MHz, CDCl3) Page S118 IR spectrum (neat) of 4k. Page S119 1H NMR (4l, 500 MHz, CDCl3) 13C NMR (4l, 126 MHz, CDCl3) Page S120 IR spectrum (neat) of 4l. Page S121 1H NMR (4m, 400 MHz, CDCl3) 13C NMR (4m, 126 MHz, CDCl3) Page S128 IR spectrum (neat) of 4p. Page S129 1H NMR (4q, 500 MHz, CDCl3) 13C NMR (4q, 101 MHz, CDCl3) Page S130 IR spectrum (neat) of 4q. Page S131 1H NMR (4q´, 500 MHz, CDCl3) 13C NMR (4q´, 101 MHz, CDCl3) Page S132 IR spectrum (neat) of 4q´. Page S133 1H NMR (4l´, 500 MHz, CDCl3) 13C NMR (4l´, 126 MHz, CDCl3) Page S134 IR spectrum (neat) of 4l´. Page S135 1H NMR (5, 400 MHz, CDCl3) 13C NMR (5, 101 MHz, CDCl3) Page S136 IR spectrum (neat) of 5. Page S137 1H NMR (6, 500 MHz, CDCl3) 13C NMR (6, 126 MHz, CDCl3) Page S144 IR spectrum (neat) of 9. Page S145 1H NMR (10, 500 MHz, CDCl3) 13C NMR (10, 126 MHz, CDCl3) Page S146 IR spectrum (neat) of 10. Page S147 1H NMR (11, 500 MHz, CDCl3) 13C NMR (11, 126 MHz, CDCl3) Page S148 IR spectrum (neat) of 11. Page S149 11. X-ray molecular structures CCDC 2455402 (2a), 2455403 (4a) and 2456253 (4l) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Experimental: The measured crystals of compounds 2a, 4a and 4l grown from a combination of CH2Cl2, EtOAc and hexane, were stable under atmospheric conditions; nevertheless, they were treated under inert conditions immersed in perfluoro-polyether as protecting oil for manipulation. Data Collection: measurements were made on a BrukerNonius diffractometer equipped with an APPEX II 4K CCD area detector, a FR591 rotating anode with MoKα radiation, Montel mirrors and a Kryoflex low temperature device (T = −173 °C). Full-sphere data collection was used with ω and φ scans. Programs used: Data collection Apex2 V2011.3 (Bruker-Nonius 2008), data reduction Saint+Version 7.60A (Bruker AXS 2008) and absorption correction SADABS V. 2008−1 (2008). Structure Solution: SHELXTL Version 6.10 (Sheldrick, 2000) was used. Structure Refinement was done using SHELXTL-97-UNIX VERSION. Page S150 Molecular structure for 2a (CCDC-2455402): Page S151 Molecular structure for 4a (CCDC-2455403): Page S152 Molecular structure for 4l (CCDC-2456253): Page S153 12. References [1] W. Shi, C. Qiao, J. Benet-Buchholz, A. W. Kleij, ChemSusChem 2024, 17, e202301626. [2] C. J. Whiteoak, N. Kielland, V. Laserna, E. C. Escudero-Adán, E. Martin, A. W. Kleij, J. Am. Chem. Soc. 2013, 135, 1228-1231.