Corresponding Authors: Supporting Information, Part I Experimental Procedures and X-Ray Crystallographic Data SI- 1

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1 Scalable C Oxidation with Copper: Synthesis of Polyoxypregnanes Yi Yang See, Aaron T. errmann, Yoshinori Aihara, Phil S. Baran* The Scripps Research Institute, North Torrey Pines Road, La Jolla, CA Corresponding Authors: pbaran@scripps.edu Supporting Information, Part I Experimental Procedures and X-Ray Crystallographic Data SI- 1

2 SUPPORTING INFORMATION Table of Contents General Procedures... SI-3 Current chanism Proposed by Schönecker... SI-4 Experimental Procedures Compound S1... SI-5 Standard procedure for imine formation... SI-6 Compound S2... SI-7 Compound S3... SI-8 Compound S4... SI-9 Compound S5... SI-10 Compound S7... SI-11 Compound S8... SI-12 Compound S9... SI-13 Compound S11... SI-14 Compound S13... SI-15 Compound S14... SI-15 Standard procedure for Schönecker oxidation... SI-16 Pictorial guide for Schönecker oxidation... SI-17 Compound 7... SI-25 Compound 8... SI-26 Compound 9... SI-27 Compound SI-28 Compound SI-29 Compound SI-30 Compound SI-31 Compound SI-32 Compound SI-33 Optimization Table for Cyclopropane Alkene Formation... SI-34 Compound 5... SI-35 Compound S15... SI-36 Compound S17... SI-37 Compound SI-38 Compound SI-39 Compound SI-40 Compound 2, pergularin... SI-42 Natural product NMR comparison tables for pergularin 2... SI-43 Compound 1, utendin... SI-44 Natural product NMR comparison tables for utendin 1... SI-45 Compound 3, tomentogenin... SI-46 Natural product NMR comparison tables for tomentogenin 3... SI-47 X-Ray Crystallographic Data Compound 5... SI-48 Compound SI-63 Compound S15... SI-73 Compound SI-96 Compound SI-107 Compound SI-118 Compound 3, tomentogenin... SI-128 References... SI-139 SI- 2

3 General Procedures. All reactions were performed using flame-dried round-bottomed flasks or reaction vessels unless otherwise stated. Where appropriate, reactions were carried out under an inert atmosphere of argon with dry solvents, unless otherwise stated. Dry dichloromethane (DCM), tetrahydrofuran (TF), ether (Et 2 O), N,N-dimethylformamide (DMF), N,Ndimethylacetamide (DMA), toluene (Ph), benzene (Ph), acetonitrile (CN) and methanol (O) were obtained by passing the previously degassed solvents through activated alumina columns. Yields refer to chromatographically and spectroscopically ( 1 NMR) homogeneous materials, unless otherwise stated. Reagents were purchased at the highest commercial quality and used without further purification, unless otherwise stated. Reactions were monitored by thinlayer chromatography carried out on 0.25 mm E. rck silica gel plates (60F-254) using ultraviolet light as visualizing agent and an acidic mixture of p-anisaldehyde or a basic mixture of potassium permanganate and heat as developing agents. NMR spectra were recorded on a Bruker DRX-600, DRX-500 or AMX-400 spectrometer and were calibrated using residual undeuterated solvent as an internal reference (CDCl 3 : 1 NMR = 7.26, 13 C NMR = 77.16, thanol-d4: 1 NMR = 3.31, 13 C NMR = 49.15, Pyridine-d5: 1 NMR = 7.22, 13 C NMR = ). The following abbreviations or combinations thereof were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad. igh resolution mass spectra (RMS) were recorded on an Agilent Mass spectrometer using ESI- TOF (electrospray ionization-time of flight). lting points were recorded on a Fisher-Johns melting point apparatus. The UCSD small molecule X-ray facility collected and analyzed all X-ray diffraction data. SI- 3

4 Current chanism Proposed by Schönecker O N O 12 N N Cu(I) O 2 N Cu III O O Cu III N N 12 N O O N N N 12 A O B O A chanistically, the entirety of what is currently known about this reaction is summarized in the figure directly above. By analogy to its enzymatic counterpart it is believed that the starting pyridyl imine (A) captures a Cu(I) species which is subsequently oxidized with molecular oxygen to a dimeric species (B). The remaining steps are not well understood but presumably involve a radical rebound type C oxidation of the C 12 position. Upon workup, the unknown Cuspecies is de-complexed to release the oxidized product 7 (maximum 50% yield) and unreacted starting material A. SI- 4

5 2 N N S1 Compound S1. Experimental: A solution of 4-methyl-2-pyridinecarbonitrile (10.0 g, 84.6 mmol) in TF (85 ml, 3 rinses total) was added (as a slow stream) to a mixture of LiAl 4 (4.82 g, mmol, 1.5 equiv) in TF (130 ml) at 0 C and stirred for 1.5 h at 0 C. Feiser workup: The reaction was quenched with water (4.8 ml) at 0 C and stirred for 5 min. Then aqueous sodium hydroxide (3 M, 4.8 ml) was added at 0 C and stirred for 5 min and warmed to rt. Then additional water (14.4 ml) was added and the reaction was stirred for 2h. The reaction mixture was filtered and then concentrated in vacuo. The residue was purified by Kugelrohr distillation (130 C, 20 mmg) to afford product S1 1 as a yellow oil (6.00 g, 73.3 mmol, 86%). Physical state: yellow oil 1 NMR (400 Mz, Chloroform-d) δ 8.38 (d, J = 5.0 z, 1), 7.08 (s, 1), 6.95 (d, J = 5.0 z, 1), 3.91 (d, J = 1.5 z, 2), 2.32 (s, 3), 1.68 (d, J = 18.6 z, 2). 13 C NMR (151 Mz, Chloroform-d) δ 161.6, 149.1, 147.9, 123.0, 122.3, 47.7, SI- 5

6 General Procedure for Imine Formation O 2 N N S1 N N Standard Procedure 1: Imine formation In a flame-dried flask, amine S1 (2.20 equiv) was added to the substrate ketone and p- toluenesulfonic acid monohydrate (cat. 20 mg) in toluene (0.35 M). The reaction mixture was heated to reflux in a Dean-Stark apparatus until imine formation was complete (monitored by 1 NMR, reaction is normally ca. 12 h). The reaction was cooled to room temperature and diluted with diethyl ether (30 ml). The organic was washed sequentially with saturated aqueous ammonium chloride (2 x 20 ml), saturated aqueous sodium bicarbonate (1 x 20 ml), brine (1 x 20 ml), and dried over sodium sulfate, then concentrated in vacuo. Standard Procedure 2: Imine formation In a flame-dried flask, amine S1 (2.20 equiv) was added to the substrate ketone and 4 Å MS (120 wt%, pre-activated by heating with a flame torch under high vacuum) in toluene (0.35 M). The reaction mixture was heated to reflux in a Dean-Stark apparatus until imine formation was complete (monitored by 1 NMR, reaction is normally ca. 12 h). The reaction was cooled to room temperature and diluted with diethyl ether (30 ml). The organic was washed sequentially with saturated aqueous ammonium chloride (2 x 20 ml), saturated aqueous sodium bicarbonate (1 x 20 ml), brine (1 x 20 ml), and dried over sodium sulfate, then concentrated in vacuo. Further purification The crude substrate was triturated with diethyl ether (25 ml) and the resulting solid was dried in vacuo. SI- 6

7 N N O Compound S2. Experimental: The title compound was prepared from dehydro-epi-androsterone (0.577 g, 2.0 mmol) following the standard imine formation procedure 1. There was no further purification and crude product S2 was obtained as a white solid (quantitative). Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ 8.35 (d, J = 5.0 z, 1), 7.23 (s, 1), 6.94 (d, J = 5.1 z, 1), 5.35 (d, J = 5.3, 1), 4.58 (d, J = 16.5 z, 1), 4.50 (d, J = 16.5 z, 1), 3.51 (tt, J = 11.1, 4.7 z, 1 ), 2.44 (dd, J = 18.3, 9.0 z, 1), (m, 3 ), 2.32 (s, 3), 2.14 (brs, 1), (m, 2), (m, 3), (m, 3), (m, 4), (m, 1), 1.09 (td, J = 13.5, 3.6 z, 1), (m, 1), 1.03 (s, 3), 0.91 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 186.0, 160.3, 148.8, 147.8, 141.4, 122.8, 122.6, 121.2, 71.7, 58.1, 53.5, 50.7, 45.8, 42.5, 37.5, 36.9, 34.2, 31.8, 31.7, 31.5, 28.2, 23.5, 21.4, 20.9, 19.7, RMS (ESI) m/z: Calculated for C N 2 O [M+] , found SI- 7

8 N N O Compound S3 Experimental: The title compound was prepared from estrone-3-methyl ether ( g, 2.00 mmol) following the standard imine formation 2. There was no further purification needed and crude product S3 was obtained as a light orange solid (quantitative). Physical state: light orange solid 1 NMR (600 Mz, Chloroform-d) δ 8.41 (d, J = 5.0 z, 1), 7.30 (s, 1), 7.26 (d, J = 8.7 z, 1), 6.99 (d, J = 5.0 z, 1), 6.75 (dd, J = 8.6, 2.8 z, 1), 6.67 (d, J = 2.8 z, 1), 4.64 (d, J = 16.5 z, 1), 4.57 (d, J = 16.5 z, 1), 3.81 (s, 3), (m, 2), (m, 1), (m, 1), (m, 1), 2.37 (s, 3), (m, 1), (m, 1), (m, 2), (m, 4), (m, 2), 0.97 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 185.8, 160.4, 157.7, 148.9, 147.8, 138.1, 132.7, 126.6, 122.8, 122.6, 114.0, 111.7, 58.2, 55.4, 52.2, 46.2, 44.4, 38.7, 34.5, 30.0, 28.3, 27.4, 26.6, 23.4, 21.4, RMS (ESI) m/z: Calculated for C N 2 O [M+] , found SI- 8

9 N N Compound S4 Experimental: In a flame-dried flask, 2-picolylamine (2.20 ml, 21.7 mmol, 2.2 equiv) was added to (1R)-(+)-camphor (1.50 g, 9.85 mmol) following the standard imine formation procedure 1. No further purification was need to afford crude product S4 as a light orange oil (2.15 g, 8.87 mmol, 90%). Physical state: light orange oil 1 NMR (600 Mz, Chloroform-d) δ 8.43 (ddd, J = 4.9, 1.9, 0.9 z, 1), 7.56 (td, J = 7.7, 1.9 z, 1), 7.39 (dt, J = 7.8, 1.0 z, 1), (m, 1), 4.54 (d, J = 16.6 z, 1), 4.48 (d, J = 16.6 z, 1), 2.35 (dt, J = 17.1, 3.9 z, 1), 1.89 (t, J = 4.5 z, 1), 1.85 (d, J = 17.1 z, 1), (m, 1), (m, 1), (m, 1), (m, 1), 0.98 (s, 3), 0.87 (s, 3), 0.70 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 184.5, 160.7, 148.9, 136.5, 121.6, 121.5, 57.6, 54.0, 47.3, 43.9, 36.0, 32.2, 27.5, 19.7, 19.0, RMS (ESI) m/z: Calculated for C N 2 [M+] , found SI- 9

10 N N BnO Compound S5 Experimental: The title compound was prepared from known substrate S6 2 (0.757 g, 2.0 mmol) following the standard imine formation procedure 1. There was no further purification needed, affording crude product S5 as a light orange solid (quantitative). Physical state: light orange solid 1 NMR (600 Mz, Chloroform-d) δ 8.37 (d, J = 5.0 z, 0), (m, 4), 7.26 (s, 13), 6.95 (d, J = 5.1 z, 0), 5.37 (dt, J = 5.1, 1.8 z, 1), 4.59 (d, J = 16.7 z, 1), 4.57 (s, 2), 4.51 (d, J = 16.6 z, 1), 3.29 (tt, J = 11.3, 4.5 z, 1), (m, 2), 2.33 (s, 3), 2.29 (dt, J = 17.9, 9.5 z, 2), 2.07 (dddd, J = 23.0, 12.8, 4.8, 2.6 z, 2), (m, 1), (m, 2), (m, 4), (m, 2), 1.18 (ddd, J = 12.8, 10.3, 5.9 z, 1), (m, 5), 0.92 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 185.9, 160.5, 149.0, 147.8, 141.5, 139.2, 128.6, 127.8, 127.6, 122.8, 122.6, 121.3, 78.7, 70.2, 58.2, 53.5, 50.8, 45.8, 39.4, 37.5, 37.3, 34.3, 31.8, 31.6, 28.6, 28.2, 23.6, 21.4, 21.0, 19.7, RMS (ESI) m/z: Calculated for C N 2 O [M+] , found SI- 10

11 N N O Compound S7 Experimental: The title compound was prepared from trans-androsterone (0.757 g, 2.0 mmol) following the standard imine formation procedure 1. There was no further purification needed, affording crude product S7 as a light orange solid (quantitative). Physical state: light orange solid 1 NMR (600 Mz, Chloroform-d) δ 8.37 (dd, J = 5.0, 0.7 z, 1), 7.24 (s, 1), 6.95 (dd, J = 5.1, 0.9 z, 1), 4.58 (d, J = 16.5 z, 1), 4.51 (d, J = 16.6 z, 1), (m, 1), (m, 1), 2.33 (s, 3), (m, 1), (m, 1), (m, 4), (m, 1), (m, 1), 1.52 (qd, J = 11.0, 4.1 z, 1), (m, 8), (m, 2), (m, 2), 0.89 (s, 3), 0.85 (s, 3), (m, 1). 13 C NMR (151 Mz, Chloroform-d) δ 186.1, 160.5, 148.9, 147.8, 122.8, 122.6, 71.5, 58.2, 55.0, 53.2, 46.0, 45.1, 38.4, 37.2, 35.9, 35.4, 34.4, 31.6, 31.7, 28.8, 28.2, 23.5, 21.4, 21.2, 16.7, 12.6 RMS (ESI) m/z: Calculated for C N 2 O [M+] , found SI- 11

12 N N Compound S8 Experimental: The title compound was prepared from substrate 5 3 (3.79 g, 14.0 mmol) following the standard imine formation 1. There was no further purification needed, affording crude product S8 as a light orange solid (quantitative). Physical state: light orange solid 1 NMR (600 Mz, Chloroform-d) δ 8.33 (d, J = 5.0 z, 1), (m, 1), (m, 1), 5.54 (dd, J = 9.8, 1.8 z, 1), 5.21 (dd, J = 9.8, 2.6 z, 1), 4.56 (d, J = 16.5 z, 1), 4.49 (d, J = 16.5 z, 1), 2.45 (dd, J = 18.3, 9.0 z, 1), (m, 1), 2.29 (s, 3), (m, 1), (m, 1), (m, 1), (m, 3), (m, 2), (m, 2), (m, 1), (m, 1), 1.14 (dt, J = 8.3, 4.4 z, 1), (m, 1), 0.93 (s, 3), 0.91 (s, 3), 0.79 (t, J = 4.8 z, 1), 0.43 (dd, J = 8.1, 5.1 z, 1). 13 C NMR (151 Mz, Chloroform-d) δ 185.5, 160.3, 148.8, 147.7, 132.6, 126.0, 122.7, 122.5, 58.0, 51.7, 46.61, 46.60, 42.8, 36.7, 36.2, 34.6, 31.6, 28.2, 25.9, 25.2, 23.4, 22.0, 21.3, 18.0, 16.7, RMS (ESI) m/z: Calculated for C N 2 [M+] , found SI- 12

13 N N TBSO Compound S9 Experimental: The title compound was prepared from substrate S10 4 (0.757 g, 2.0 mmol) following the standard imine formation procedure 2. There was no further purification needed, affording crude product S9 as a light orange solid (quantitative). Physical state: light orange solid 1 NMR (600 Mz, Chloroform-d) δ 8.37 (d, J = 5.0 z, 1), 7.25 (s, 1), (m, 1), 5.34 (d, J = 5.4 z, 1), 4.59 (d, J = 16.5 z, 1), 4.51 (d, J = 16.5 z, 1), (m, 1), 2.45 (dd, J = 18.5, 8.5 z, 1), 2.33 (s, 3), (m, 2), (m, 1), (m, 2), (m, 2), (m, 4), 1.54 (m, 2), (m, 2), (m, 1), (m, 2), 1.04 (s, 3), 0.92 (s, 3), 0.89 (s, 9), 0.06 (s, 6). 13 C NMR (151 Mz, Chloroform-d) δ 186.0, 160.5, 148.9, 147.8, 142.1, 122.8, 122.6, 120.9, 72.8, 58.2, 53.6, 50.8, 45.8, 43.0, 37.6, 37.0, 34.3, 32.3, 31.8, 31.6, 28.3, 26.2, 23.6, 21.4, 21.0, 19.7, 18.5, 16.5, RMS (ESI) m/z: Calculated for C N 2 OSi [M+] , found SI- 13

14 N N AcO Compound S11 Experimental: The title compound was prepared from substrate S12 5 (0.757 g, 2.0 mmol) following the standard imine formation procedure 1. There was no further purification needed, affording crude product S11 as a light orange solid (quantitative). Physical state: light orange solid 1 NMR (600 Mz, Chloroform-d) δ 8.37 (dd, J = 5.0, 0.8 z, 1), 7.24 (dt, J = 1.7, 0.8 z, 1), 6.95 (d, J = 5.0 z, 1), 5.40 (d, J = 5.3 z, 1), (m, 1), 4.59 (d, J = 16.8 z, 1), 4.52 (d, J = 16.6 z, 1), (m, 1), (m, 3), 2.33 (s, 3), (m, 2), 2.03 (s, 3), (m, 3), (m, 7), (m, 2), (m, 1), 1.06 (s, 3), 0.92 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 185.9, 170.8, 160.4, 148.9, 147.8, 140.2, 122.8, 122.6, 122.3, 74.1, 58.2, 53.4, 50.6, 45.8, 38.3, 37.2, 37.0, 34.2, 31.7, 31.5, 28.2, 28.0, 23.6, 21.7, 21.4, 20.9, 19.6, RMS (ESI) m/z: Calculated for C N 2 O 2 [M+] , found SI- 14

15 O O Tf 2 O, 2,4,6-collidine, C 2 Cl 2, -78 C; i-pr 2 N 2, -78 C 0 C 67% i-pr 2 N O imine formation 2 quantitative i-pr 2 N N N Compound S13 Experimental: Trifluoromethanesulfonic anhydride (1.75 ml, 10.4 mmol, 1.50 equiv) in C 2 Cl 2 (18.0 ml) was added dropwise to a pre-cooled (-78 C) solution of dehydro-epi-androsterone (2.00 g, 6.93 mmol) and 2,4,6-collidine (1.50 ml, 11.1 mmol, 1.60 equiv) in C 2 Cl 2 (14.0 ml). The reaction mixture was stirred at -78 C for 30 min, then a pre-cooled solution (-78 C) of diisopropylamine (9.70 ml, 69.0 mmol, 10.0 equiv) was slowly added to the reaction solution. The reaction mixture was warmed from -78 C to rt over 1.5 h. The reaction was quenched with saturated aqueous NaCO 3 (20 ml), and the layers were separated. The aqueous layer was extracted with C 2 Cl 2 (3 x 10 ml). The combined organic layers were washed with 1 M Cl (20 ml), dried over Na 2 SO 4, and concentrated in vacuo. The crude residue was purified by column chromatography (pre-washed with 5% triethylamine hexanes silica, 85:15 hexanes:etoac to 1:3 hexanes:etoac) to give substrate S14 (1.73 g, 4.64 mmol, 67%) as a white solid. Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ 5.27 (d, J = 5.0 z, 1), 3.13 (hept, J = 6.4 z, 2), 2.55 (tt, J = 12.1, 3.8 z, 1), 2.43 (dd, J = 19.3, 8.8 z, 1), 2.35 (td, J = 12.9, 2.6 z, 1), (m, 2), (m, 2), (m, 2), (m, 5), 1.52 (tt, J = 12.5, 9.1 z, 1), 1.44 (td, J = 13.3, 4.2 z, 2), (m, 2), 1.07 (td, J = 13.3, 4.0 z, 1), (m, 14), 0.86 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 221.4, 144.1, 119.0, 54.7, 52.0, 50.7, 47.7, 44.8, 40.3, 39.1, 37.0, 36.0, 31.8, 31.7, 31.1, 29.4, 23.4, 23.3, 22.1, 20.5, 19.7, RMS (ESI) m/z: Calculated for C NO [M+] , found MP: C [α] D (c 1.0, CCl 3 ) The title compound was prepared from substrate S14 (0.757 g, 2.0 mmol) following the standard imine formation procedure 2. There was no further purification needed, affording crude product S13 as a light orange solid (quantitative). Physical state: light orange solid 1 NMR (600 Mz, Chloroform-d) δ 8.40 (d, J = 5.0 z, 1), 7.25 (s, 1), 6.98 (d, J = 5.1 z, 1), 5.32 (d, J = 5.5 z, 1), 4.62 (d, J = 16.6 z, 1), 4.54 (d, J = 16.6 z, 1), 3.18 (hept, J = 6.5 z, 2), 2.60 (ddt, J = 12.1, 7.5, 3.8 z, 1), (m, 1), (m, 2), 2.36 (s, 3), (m, 1), (m, 3), (m, 8), (m, 1), (m, 3), 1.04 (s, 3), 1.03 (t, J = 6.5 z, 12), 0.95 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 186.1, 160.5, 148.9, 147.8, 144.3, 122.8, 122.6, 119.3, 58.2, 54.8, 53.6, 51.1, 45.8, 44.8, 40.4, 39.2, 37.1, 34.4, 31.9, 31.6, 29.5, 28.3, 23.6, 23.5, 23.4, 21.4, 21.0, 19.8, RMS (ESI) m/z: Calculated for C N 3 [M+] , found SI- 15

16 General Procedure for Schönecker Oxidation Standard Procedure 1: Schönecker Oxidation using [Cu(CN) 4 PF 6 ] The imine substrate (0.50 mmol), copper(i) tetrakis(acetonitrile) hexafluorophosphate (0.242 g, 0.65 mmol, 1.30 equiv), (+)-sodium-(l)-ascorbate (0.198 g, 1.00 mmol, 2.00 equiv) were added to a round-bottom-flask (RBF). Acetone (1.65 ml) and methanol (1.65 ml) were added at room temperature and stirred for 5 min (reaction mixture is brown). O 2 from a balloon was bubbled through the reaction mixture for 5 min (resulting in a blue/green solution), after which the reaction was heated to 50 C under an O 2 atmosphere for 1.5 h. The reaction mixture was then cooled to room temperature, ethyl acetate (3 ml) and saturated aqueous Na 4 EDTA (6 ml, p ~10) were added and the reaction mixture was stirred for 1 h. The layers were separated. The aqueous layer was extracted with ethyl acetate (3 x 10 ml), dried over sodium sulfate, and concentrated in vacuo. The crude product was purified by flash column chromatography. Standard Procedure 2: Schönecker Oxidation using Cu(OTf) 2 The imine substrate (0.50 mmol), copper(ii) triflate (0.235 g, 0.65 mmol, 1.30 equiv), (+)- sodium-(l)-ascorbate (0.198 g, 1.00 mmol, 2.00 equiv) were added to a round-bottom-flask (RBF). Acetone (1.65 ml) and methanol (1.65 ml) were added at room temperature and stirred for 5 min (reaction mixture may turn brown). O 2 from a balloon was bubbled through the reaction mixture for 5 min (resulting in a blue/green solution), after which the reaction was heated to 50 C under an O 2 atmosphere for 1.5 h. The reaction mixture was then cooled to room temperature, ethyl acetate (3 ml) and saturated aqueous Na 4 EDTA (6 ml, p ~10) were added and the reaction mixture was stirred for 1 h. The layers were separated. The aqueous layer was extracted with ethyl acetate (3 x 10 ml), dried over sodium sulfate, and concentrated in vacuo. The crude product was purified by flash column chromatography. Note about work-up: The imine is usually partially hydrolyzed during the EDTA work-up but full hydrolysis occurs upon column chromatography. SI- 16

17 Pictorial guide for Schönecker Oxidation Schönecker Oxidation using [Cu(CN) 4 PF 6 ] Addition of DEA imine, Cu(CN) 4 PF 6, and L-ascorbic acid sodium salt to RBF Addition of acetone followed by methanol to RBF (reaction mixture will be a brown color) SI- 17

18 O 2 is bubbled through the reaction mixture for 5 min. Reaction mixture turns from brown to blue/green color SI- 18

19 Reaction is heated to 50 C for 1.5 h under O 2 TLC: Lane 1: starting material (imine) Lane 2: co-spot Lane 3: rxn spot Elution solvent: 1:1 hexanes:etoac Stain: anisaldehyde. TLC Notes: Imine partial hydrolyzes on the TLC to the corresponding ketone. Aqueous saturated EDTA Na 4 solution is spotted on the co-spot and rxn spot (to break up the allow the copper complex). EDTA spot is white Reaction is removed from heat and cooled to room temperature SI- 19

20 Aqueous saturated Na 4 EDTA solution (3 ml) and ethyl acetate (6 ml) added to the reaction mixture. Reaction mixture is stirred for 1 h. Two distinct layers are seen: -blue/green layer is aqueous -orange/brown layer is organic Crude product is separated (more water and ethyl acetate can be added to aid in the separation of layers), then extracted with ethyl acetate (3 x 10 ml). Organic layer is dried over sodium sulfate SI- 20

21 Crude product is concentrated in vacuo. Dried crude product SI- 21

22 Schönecker Oxidation using Cu(OTf) 2 Addition of DEA imine, Cu(OTf) 2, and L- ascorbic acid sodium salt to RBF Addition of acetone followed by methanol to RBF (reaction mixture will be green/blue color). SI- 22

23 After a short period of time the reaction mixture will turn to a brown color. O 2 is bubbled through the reaction mixture for 5 min. Reaction mixture turns from brown to blue/green color. SI- 23

24 Reaction is heated to 50 C for 1.5 h under O 2 Reaction is cooled to room temperature See [Cu(CN) 4 PF 6 ] pictorial guide for reaction experimental work-up (vide supra) SI- 24

25 Compound 7 (Table 2, entry 1). Experimental: The title compound was prepared from S2 (0.196 g, 0.50 mmol) following the standard Schönecker oxidation 1. The residue was purified by column chromatography (vide supra) to afford product 7 as a white solid (0.137 g, 0.45 mmol, 90%). The title compound was prepared from S2 (0.196 g, 0.50 mmol) following the standard Schönecker oxidation 2. The residue was purified by column chromatography (silica, 2:3 hexanes:etoac to 1:9 hexanes:etoac) to afford product 7 6 as a white solid (0.104 g, 0.34 mmol, 68%). Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ (m, 1), 3.79 (dd, J = 11.3, 4.7 z, 1), (m, 1), 3.10 (s, 1), 2.46 (dd, J = 19.5, 9.0 z, 1), 2.31 (ddd, J = 13.1, 5.0, 2.2 z, 1), (m, 1), (m, 2), (m, 1), (m, 3), (m, 3), (m, 2), (m, 1), (m, 2), 1.03 (s, 3), 0.94 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 223.0, 141.2, 120.9, 72.8, 71.6, 51.6, 49.7, 49.3, 42.3, 37.3, 36.9, 35.9, 31.7, 30.8, 30.5, 28.4, 21.9, 19.5, 8.2. SI- 25

26 O O O Compound 8 (Table 2, entry 2) Experimental: The title compound was prepared from S3 (0.194 g, 0.50 mmol) following the standard Schönecker oxidation 1. The residue was purified by column chromatography (vide supra) to afford product 8 as a white solid (93 mg, 0.31 mmol, 62%). The title compound was prepared from S3 (0.194 g, 0.50 mmol) following the standard Schönecker oxidation 2. The residue was purified by column chromatography (silica, 1:1 hexanes:etoac to 1:3 hexanes:etoac) to afford product 8 7 as a white solid (95 mg, 0.32 mmol, 64%) Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ 7.18 (dd, J = 8.6, 1.1 z, 1), 6.72 (dd, J = 8.6, 2.8 z, 1), 6.65 (d, J = 2.7 z, 1), 3.98 (dd, J = 11.3, 4.6 z, 1), 3.78 (s, 3), 3.08 (s, 1), (m, 2), (m, 2), (m, 1), 2.17 (dt, J = 19.2, 8.9 z, 1), (m, 1), (m, 1), 1.74 (tt, J = 12.3, 9.0 z, 1), (m, 4), 0.98 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 222.8, 157.9, 137.7, 131.3, 126.3, 114.2, 111.7, 72.8, 55.4, 52.2, 48.6, 42.4, 37.5, 36.0, 33.2, 29.7, 26.4, 21.6, 8.5 RMS (ESI) m/z: Calculated for C O 3 [M+] , found SI- 26

27 Compound 9 (Table 2, entry 3) Experimental: The imine substrate S4 (0.121 g, 0.50 mmol), copper(i) tetrakis(acetonitrile) hexafluorophosphate (0.242 g, 0.65 mmol, 1.30 equiv), (+)-sodium-(l)-ascorbate (0.198 g, 1.00 mmol, 2.00 equiv) were added to a RBF. Acetone (1.65 ml) and methanol (1.65 ml) were then added at room temperature and stirred for 5 min. O 2 gas was bubbled through the reaction mixture for 5 min then heated to 50 C under an O 2 atmosphere for 3 h. Additional copper(i) tetrakis(acetonitrile) hexafluorophosphate (0.186 g, 0.50 mmol, 1.00 equiv), (+)-sodium-(l)- ascorbate (99 mg, 0.50 mmol, 1.00 equiv) were added and heated at 50 C for an additional 3 h. The reaction mixture was cooled to room temperature, and ethyl acetate (3 ml) and saturated aqueous Na 4 EDTA (6 ml, p ~10) were added and the reaction mixture was stirred for 15 h. The layers were separated. The aqueous layer was extracted with ethyl acetate (3 x 10 ml), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography (vide supra) to afford product 9 as a white solid (79 mg, 0.47 mmol, 94%). The imine substrate S4 (0.121 g, 0.50 mmol), copper(ii) triflate (0.235 g, 0.65 mmol, 1.30 equiv), (+)-sodium-(l)-ascorbate (0.198 g, 1.00 mmol, 2.00 equiv) were added to a RBF. Acetone (1.65 ml) and methanol (1.65 ml) were then added at room temperature and stirred for 5 min. O 2 gas was bubbled through the reaction mixture for 5 min then heated to 50 C under an O 2 atmosphere for 3 h. Additional copper(ii) triflate (0.181 g, 0.50 mmol, 1.00 equiv), (+)- sodium-(l)-ascorbate (99 mg, 0.50 mmol, 1.00 equiv) were added and heated at 50 C for an additional 3 h. The reaction mixture was cooled to room temperature, and ethyl acetate (3 ml) and saturated aqueous Na 4 EDTA (6 ml, p ~10) were added and the reaction mixture was stirred for 15 h. The layers were separated. The aqueous layer was extracted with ethyl acetate (3 x 10 ml), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography (silica, 50% ethyl acetate hexanes) to afford product 9 8 as a white solid (72 mg, 0.43 mmol, 87%). Note: To facilitate isolation of the ketone, stirring for 15 h was necessary to hydrolyze the imine completely. Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ 3.87 (dd, J = 12.0, 4.8 z, 1), 3.64 (dd, J = 11.9, 7.6 z, 1), 2.53 (dd, J = 7.9, 5.3 z, 1), (m, 1), 2.07 (t, J = 4.5 z, 1), (m, 1), 1.86 (d, J = 18.5 z, 1), (m, 1), 1.59 (ddd, J = 14.0, 9.4, 4.8 z, 1), 1.39 (ddd, J = 13.0, 9.3, 4.0 z, 1), 1.00 (s, 3), 0.98 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 221.2, 61.9, 60.8, 47.0, 44.2, 43.7, 26.9, 26.2, 21.0, SI- 27

28 Compound 10 (Table 2, entry 4) Experimental: The title compound was prepared from S5 (0.241 g, 0.50 mmol) following the standard Schönecker oxidation 1. The residue was purified by column chromatography (vide supra) to afford product 10 as a white solid (0.109 g, 0.28 mmol, 55%). The title compound was prepared from S5 (0.241 g, 0.50 mmol) following the standard Schönecker oxidation 2. The residue was purified by column chromatography (silica, 7:3 hexanes:etoac to 2:3 hexanes:etoac) to afford product 10 9 as a white solid (0.144 g, 0.37 mmol, 73%). Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ (m, 3), (m, 2), (m, 1), 4.57 (s, 2), 3.81 (dd, J = 11.3, 4.7 z, 1), 3.29 (tt, J = 11.3, 4.5 z, 1), 3.11 (brs, 1), (m, 2), (m, 1), (m, 2), (m, 2), 1.88 (dt, J = 13.3, 3.5 z, 1), 1.82 (dt, J = 13.2, 4.7 z, 1), (m, 4), (m, 1), (m, 1), (m, 2), 1.06 (s, 3), 0.97 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 222.9, 141.3, 139.1, 128.5, 127.7, 127.6, 120.8, 78.4, 72.8, 70.1, 51.5, 49.7, 49.3, 39.2, 37.3, 37.2, 35.9, 30.7, 30.6, 28.4, 28.3, 21.8, 19.5, 8.2. SI- 28

29 Compound 11 (Table 2, entry 5) Experimental: The title compound was prepared from S7 (0.197 g, 0.50 mmol) following the standard Schönecker oxidation 1. The residue was purified by column chromatography (vide supra) to afford product 11 as a white solid (0.123 g, 0.40 mmol, 80%). The title compound was prepared from S7 (0.197 g, 0.50 mmol) following the standard Schönecker oxidation 2. The residue was purified by column chromatography (silica, 2:3 hexanes:etoac to 1:4 hexanes:etoac) to afford product as a white solid (0.101 g, 0.33 mmol, 66%). Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ 3.74 (dd, J = 11.3, 4.7 z, 1), 3.58 (tt, J = 11.1, 4.8 z, 1), 3.00 (s, 1), 2.44 (ddd, J = 19.5, 9.0, 1.1 z, 1), (m, 1), (m, 1), (m, 3), (m, 2), (m, 4), (m, 6), 1.11 (tt, J = 12.5, 3.3 z, 1), (m, 1), 0.93 (s, 3), 0.83 (s, 3), 0.79 (ddd, J = 12.8, 10.6, 4.2 z, 1). 13 C NMR (151 Mz, Chloroform-d) δ 223.2, 73.0, 71.3, 52.9, 51.9, 49.4, 45.0, 38.1, 37.1, 36.0, 35.9, 34.3, 31.7, 30.6, 28.6, 28.5, 21.9, 12.4, 8.5. SI- 29

30 O O Compound 12 Experimental: The title compound was prepared from S8 (1.31 g, 3.50 mmol) following the standard Schönecker oxidation 1. The residue was purified by column chromatography (vide supra) to afford product 12 as a white solid (0.403 g, 1.41 mmol, 40%). The title compound was prepared from S8 (0.187 g, 0.50 mmol) following the standard Schönecker oxidation 2. The residue was purified by column chromatography (silica, 30% ethyl acetate hexanes) to afford product 12 as a white solid (3 mg, 0.01 mmol, 2%). Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ 5.53 (dd, J = 9.7, 1.8 z, 1), 5.26 (dd, J = 9.8, 2.6 z, 1), (m, 1), 2.98 (brs, 1), (m, 1), (m, 1), (m, 2), (m, 4), 1.61 (dd, J = 12.0, 7.8 z, 1), (m, 1), (m, 2), 1.17 (dt, J = 8.3, 4.3 z, 1), 0.99 (s, 3), (m, 1 ), 0.92 (s, 3), 0.83 (t, J = 4.8 z, 1), 0.48 (dd, J = 8.1, 5.2 z, 1). 13 C NMR (126 Mz, Chloroform-d) δ 222.5, 133.5, 124.0, 73.1, 52.6, 48.2, 44.5, 42.9, 36.9, 36.0, 35.1, 31.7, 29.3, 26.0, 25.2, 21.9, 18.0, 14.9, 8.5. RMS (ESI) m/z: Calculated for C O 2 [M+] , found MP: C [α] D (c 1.0, CCl 3 ) TLC: R f 0.43 (7:3 hexanes:ethyl acetate, anisaldehyde [blue]) X-Ray: for coordinates see page SI-63 SI- 30

31 Compound 13 (Table 2, entry 7) Experimental: The title compound was prepared from S9 (0.253 g, 0.50 mmol) following the standard Schönecker oxidation 1. The residue was purified by column chromatography (vide supra) to afford the product 13 as a white solid (0.108 g, 0.26 mmol, 52%). The title compound was prepared from S9 (0.253 g, 0.50 mmol) following the standard Schönecker oxidation 2. The residue was purified by column chromatography (silica, 4:1 hexanes:etoac to 3:2 hexanes:etoac) to afford the product 13 as a white solid (0.106 g, 0.25 mmol, 51%). Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ (m, 1), 3.78 (dd, J = 11.3, 4.7 z, 1), 3.46 (tt, J = 11.0, 4.8 z, 1), 3.07 (s, 1), 2.45 (dd, J = 19.6, 8.8 z, 1), (m, 1), 2.18 (m, 1), (m, 2), (m, 1), (m, 2), (m, 1), (m, 3), (m, 1), (m, 1), 1.23 (ddd, J = 12.6, 10.5, 5.9 z, 1), (m, 2), 1.02 (s, 3), 0.94 (s, 3), 0.87 (s, 9), 0.04 (s, 6). 13 C NMR (151 Mz, Chloroform-d) δ 222.9, 141.9, 120.4, 72.9, 72.5, 51.6, 49.8, 49.4, 42.9, 37.4, 37.0, 35.9, 32.2, 30.8, 30.6, 28.4, 26.1, 21.9, 19.6, 18.4, 8.2, -4.40, RMS (ESI) m/z: Calculated for C O 3 Si [M+] , found MP: C [α] D (c 1.0, CCl 3 ) TLC: R f 0.44 (7:3 hexanes:etoac, anisaldehyde [blue]) SI- 31

32 Compound 14 (Table 2, entry 8) Experimental: The title compound was prepared from S11 (0.217 g, 0.50 mmol) following the standard Schönecker oxidation 1. The residue was purified by column chromatography (vide supra) to afford product 14 as a white solid (78 mg, 0.23 mmol, 46%). The title compound was prepared from S11 (0.217 g, 0.50 mmol) following the standard Schönecker oxidation 2. The residue was purified by column chromatography (silica, 4:1 hexanes:etoac to 2:3 hexanes:etoac) to afford product 14 as a white solid (0.105 g, 0.30 mmol, 61%). Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ (m, 1), 4.57 (tt, J = 11.6, 4.6 z, 1), 3.79 (dd, J = 11.3, 4.7 z, 1), 3.06 (s, 1), 2.45 (dd, J = 19.5, 9.0 z, 1), 2.34 (ddd, J = 13.1, 5.1, 2.0 z, 1), (m, 1), (m, 2), 2.01 (s, 3), (m, 1), (m, 2), 1.78 (dt, J = 13.1, 4.7 z, 1), (m, 4), (m, 1), (m, 1), (m, 2), 1.03 (s, 3), 0.93 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 222.8, 170.6, 140.1, 121.9, 73.7, 72.7, 51.5, 49.6, 49.2, 38.2, 37.1, 37.0, 35.9, 30.7, 30.5, 28.3, 27.8, 21.8, 21.6, 19.4, 8.2. RMS (ESI) m/z: Calculated for C O 4 [M+] , found MP: C [α] D (c 1.0, CCl 3 ) TLC: R f 0.2 (7:3 hexanes:etoac, anisaldehyde [blue]) SI- 32

33 O O i-pr 2 N Compound 15 (Table 2, entry 9). Experimental: The title compound was prepared from S13 (0.238 g, 0.50 mmol) following the standard Schönecker oxidation 1. The residue was purified by column chromatography (vide supra) to afford product 15 as a white solid (60 mg, 0.16 mmol, 32%). The title compound was prepared from S13 (0.238 g, 0.50 mmol) following the standard Schönecker oxidation 2. The residue was purified by column chromatography (pre-washed with 5% triethylamine hexanes silica, 85:15 hexanes:etoac to 1:3 hexanes:etoac) to afford product 15 as a white solid (0.132 g, 0.34 mmol, 68%) Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ 5.28 (d, J = 5.2 z, 1), 3.80 (dd, J = 11.3, 4.7 z, 1), 3.14 (hept, J = 6.6 z, 2), 3.07 (s, 1), 2.56 (tt, J = 12.1, 3.9 z, 1), 2.46 (dd, J = 19.5, 8.8 z, 1), (m, 1), (m, 2), (m, 1), 1.91 (ddd, J = 13.5, 4.1, 2.2 z, 1), (m, 2), (m, 4), (m, 2), (m, 1), (m, 2), 1.00 (s, 3), (m, 12), 0.95 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 223.2, 144.2, 118.8, 73.0, 54.7, 51.6, 49.8, 49.6, 44.8, 40.3, 39.1, 37.2, 36.0, 30.9, 30.7, 29.4, 28.4, 23.5, 23.3, 21.9, 19.7, 8.3 RMS (ESI) m/z: Calculated for C NO3 [M+] , found MP: C [α] D (c 1.0, CCl 3 ) TLC: R f 0.45 (TLC pre-soaked with triethylamine, 7:3 hexanes:etoac, anisaldehyde [blue]) X-Ray: for coordinates see page SI-96 SI- 33

34 Optimization for Cyclopropyl-Alkene Formation SI- 34

35 O O O O dehydro-epi-andrsterone (DEA) Tf 2 O, 2,4,6-collidine, C 2 Cl 2 :Et 2 O, -78 C; Et 3 N 35% 5 Et 3 N S15 OTf Compound 5 Experimental: Trifluoromethanesulfonic anhydride (0.88 ml, 5.21 mmol, 1.50 equiv) in C 2 Cl 2 (9.3 ml) was added dropwise to a pre-cooled (-78 C) solution of dehydro-epi-androsterone (1.00 g, 3.47 mmol) and 2,4,6-collidine (0.73 ml, 5.55 mmol, 1.60 equiv) in C 2 Cl 2 (7.0 ml) and Et 2 O (1.7 ml). The reaction mixture was stirred at -78 C for 1 h, then a pre-cooled solution (-78 C) of triethyl amine (7.3 ml, 52 mmol, 15 equiv) was slowly added to the reaction solution. The reaction mixture was warmed from -78 C to -20 C over 5 h (by placing the reaction in a -20 C freezer overnight). The reaction was quenched with saturated aqueous NaCO 3 (20 ml), and the layers were separated. The aqueous layer was extracted with C 2 Cl 2 (3 x 10 ml). The combined organic layers were washed with 1 M Cl (20 ml), dried over Na 2 SO 4, and concentrated in vacuo. The crude mixture was triturated with diethyl ether (3 x 15 ml) (5 dissolves in diethyl ether and S15 remains a solid (1.18 g, 2.25 mmol, 65%)) and the combined organic washes were concentrated in vacuo The light orange crude residue was then purified via flash chromatography on silica gel (8:2 hexanes:etoac) to give cyclopropane alkene 5 (0.328 g, 1.21 mmol, 35%) as a white solid. On 5.25 g scale the reaction yields 1.48 g of 5 (5.46 mmol, 30%) and 6.17 g of S15 (11.84 mmol, 65%). Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ 5.57 (dd, J = 9.7, 1.8 z, 1), 5.27 (dd, J = 9.8, 2.5 z, 1), (m, 1), (m, 1), (m, 2), (m, 6), (m, 1), (m, 2), (m, 1), 1.19 (dt, J = 8.4, 4.4 z, 1), (m, 1), 0.93 (s, 3), 0.93 (s, 3), 0.83 (t, J = 4.8 z, 1), 0.48 (dd, J = 8.1, 5.2 z, 1). 13 C NMR (151 Mz, Chloroform-d) δ 221.0, 133.1, 125.1, 50.4, 48.7, 46.5, 42.9, 37.0, 36.2, 36.1, 32.0, 31.7, 26.0, 25.3, 22.1, 21.7, 18.0, 15.0, RMS (ESI) m/z: Calculated for C O [M+] , found MP: C [α] D (c 1.0, CCl 3 ) TLC: R f 0.56 (7:3 hexanes:ethyl acetate, anisaldehyde [blue]). X-Ray: for coordinates see page SI-48 SI- 35

36 Compound S15 Physical state: pale-white solid 1 NMR (600 Mz, Chloroform-d) δ (m, 1), 3.46 (q, J = 7.3 z, 6), (m, 1), 2.80 (s, 1), 2.64 (t, J = 12.7 z, 1), (m, 2), (m, 4), (m, 3), (m, 3), (m, 2), 1.40 (t, J = 7.3 z, 9), (m, 2), (m, 1), 1.03 (s, 3), 0.87 (s, 3). 13 C NMR (151 Mz, Chloroform-d) δ 220.9, 138.3, 124.6, 71.8, 53.5, 51.8, 50.1, 47.7, 38.4, 36.9, 36.0, 33.2, 31.5, 31.4, 30.9, 23.2, 22.0, 20.5, 19.6, 13.7, 9.5. RMS (ESI) m/z: Calculated for C NO [M+] , found MP: C [α] D (c 1.0, CCl 3 ) TLC: R f 0.00 (7:3 hexanes:ethyl acetate, anisaldehyde [blue]). X-Ray: for coordinates see page SI-73 SI- 36

37 O O TMSO OTMS O O TMSOTf, TEA Pd(OAc) 2 ; FeCl 3 59% 12 Compound S17 S16 S17 Experimental: In a flame-dried flask, trimethylsilyl triflate (2.80 ml, 15.5 mmol, 3.00 equiv) was added as a fast-drop to the precooled (0 C) reaction mixture of substrate 12 (1.48 g, 5.17 mmol) and triethylamine (2.90 ml, 20.7 mmol, 4.00 equiv) in C 2 Cl 2 (26 ml). The reaction mixture was stirred at 0 C for 50 min. The pale yellow reaction was quenched with saturated aqueous sodium bicarbonate (20 ml) and DI 2 O (20 ml). The layers were then separated. The aqueos layer was further extracted with C 2 Cl 2 (3 x 20 ml). The combined organic layers were dried over sodium sulfate, and then concentrated in vacuo to deliver crude S16. The crude compound was submitted to the next reaction without further purification. Pd(OAc) 2 (1.39 g, 6.20 mmol, 1.20 equiv) was added to a solution of crude substrate S16 (5.17 mmol) in acetonitrile (69 ml) at room temperature and the reaction was stirred for 12 h. Over the course of the reaction, the color turned from dark orange to black. The reaction mixture was monitored by TLC and after consumption of starting material (ca. 12h), the reaction mixture was cooled to 0 C. FeCl O (2.79 g, 10.3 mmol, 2.00 equiv) was then added in one portion at 0 C and stirring continued for 30 min at the same temperature. Following which, potassium carbonate (4.29 g, 31.0 mmol, 6.0 equiv) was added to the reaction mixture. The reaction mixture was filtered through a silica plug and concentrated in vacuo. The crude substrate was purified via flash chromatography on silica gel (7:3 hexanes:etoac to 4:6 hexanes:etoac) to give compound S17 (0.867 g, 3.05 mmol, 59%) as a light yellow solid and recovered starting material 12 (0.306 g, 1.07 mmol, 21%). Physical state: light yellow solid 1 NMR (600 Mz, Chloroform-d) δ 7.68 (dd, J = 6.0, 1.9 z, 1), 6.06 (dd, J = 6.0, 3.1 z, 1), 5.69 (d, J = 9.7 z, 1), 5.33 (dd, J = 9.7, 2.5 z, 1), 4.13 (dd, J = 10.5, 5.0 z, 1), 2.92 (s, 1), (m, 1), 2.35 (ddd, J = 11.9, 3.2, 1.9 z, 1), 1.92 (dt, J = 12.9, 4.5 z, 1), (m, 2), (m, 1), 1.49 (td, J = 13.0, 10.5 z, 1), 1.40 (ddd, J = 13.4, 9.7, 3.9 z, 1), (m, 1), 1.19 (s, 3), (m, 1), 0.97 (s, 3), 0.88 (t, J = 4.9 z, 1), 0.53 (dd, J = 8.1, 5.3 z, 1). 13 C NMR (151 Mz, Chloroform-d) δ 213.9, 159.6, 134.4, 131.8, 123.1, 71.6, 55.4, 53.5, 46.2, 43.1, 37.2, 32.4, 31.6, 29.3, 26.1, 25.2, 18.3, 16.3, 15.0 RMS (ESI) m/z: Calculated for C O 2 [M+] , found MP: C [α] D (c 1.0, CCl 3 ) TLC: R f 0.32 (7:3 hexanes:ethyl acetate, anisaldehyde [blue]) SI- 37

38 O O O O SiO 2, DIPEA, C 7 F 8 57% S17 21 Compound 21 Experimental: SiO 2 (3.15 g, 100 wt%) was added in one portion to the reaction mixture of substrate S17 (0.395 g, 1.39 mmol) and diisopropylethyl amine (15.0 ml, 86.9 mmol, 55.0 equiv) in octafluorotoluene (35 ml) at room temperature. The orange reaction mixture was stirred for 15 h (until satisfactory conversion was observed by TLC). The mixture was then filtered through a silica plug and concentrated in vacuo. The crude reaction mixture was purified via flash chromatography on silica gel (85:15 hexanes:etoac to 75:25 hexanes:etoac) to give compound 21 (0.225 g, mmol, 57%) as a clear yellow oil and recovered starting material S17 (68 mg, mmol, 17%). Physical state: clear oil 1 NMR (600 Mz, Chloroform-d) δ 5.72 (dd, J = 9.7, 1.8 z, 1), 5.66 (q, J = 2.1 z, 1), 5.37 (dd, J = 9.8, 2.5 z, 1), 3.63 (dd, J = 11.4, 4.3 z, 1), 3.07 (ddd, J = 23.2, 4.0, 1.8 z, 1), 2.87 (dt, J = 23.1, 2.3 z, 1), (m, 1), 2.74 (d, J = 1.7 z, 1), (m, 1), (m, 2), 1.62 (dd, J = 12.3, 8.0 z, 1), 1.46 (td, J = 12.7, 11.3 z, 1), (m, 2), 1.20 (s, 3), (m, 1), 0.96 (s, 3), 0.85 (t, J = 4.9 z, 1), 0.52 (dd, J = 8.1, 5.2 z, 1). 13 C NMR (151 Mz, Chloroform-d) δ 223.7, 150.3, 134.1, 122.8, 115.2, 72.8, 55.8, 44.0, 43.1, 41.8, 36.3, 31.7, 29.5, 26.2, 25.2, 17.6, 15.1, RMS (ESI) m/z: Calculated for C O [M+] , found [α] D (c 1.0, CCl 3 ) TLC: R f 0.42 (7:3 hexanes:ethyl acetate, anisaldehyde [blue]). SI- 38

39 O O O O Mn(acac) 2, PhSi 3 O 2, dioxane 67% O Compound 22 Experimental: Substrate 21 (290.0 mg, 1.02 mmol), Mn(acac) 2 (126.6 mg, 0.50 mmol, 0.50 equiv) and triphenylphosphine (535 mg, 2.04 mmol, 2.00 equiv) were taken up in anhydrous EtO (20 ml). O 2 was bubbled through the pale brown suspension for 30 min while the reaction was vigorously stirred. Phenylsilane (0.377 ml, 3.06 mmol, 3.00 equiv) was then added via syringe (1.00 equiv added every 30 min) over 1.5 h with the reaction vigorously stirred under an O 2 balloon at room temperature. The stirring was continued for a further 3 h after the silane addition. Over the course of the reaction, the pale brown suspension turns to a clear brown solution before turning dark at the end of the reaction. Saturated sodium thiosulfate (20 ml) was then added and the stirring continued under normal atmosphere for 30 min. Ethyl acetate (20 ml) and DI 2 O (20 ml) was added and the layers separated. The aqueos layer was further extracted with EtOAc (3 x 20 ml). The combined organic layers were dried over sodium sulfate, and then concentrated in vacuo to deliver crude 22. The crude mixture was then purified via flash chromatography on silica gel (3:1 hexanes:etoac to 1:1 hexanes:etoac) to give compound 22 (206 mg, mmol, 67%) as a white solid. Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ 5.74 (dd, J = 9.9, 1.2 z, 1), 5.37 (dd, J = 9.9, 2.7 z, 1), 3.55 (dd, J = 11.6, 4.1 z, 1), (m, 1), 2.45 (ddd, J = 19.2, 9.2, 1.7 z, 1), (m, 1), 2.07 (s, 1), (m, 1), 1.90 (ddd, J = 14.1, 9.6, 1.7 z, 1), (m, 2), 1.72 (dd, J = 13.9, 8.2 z, 1), 1.66 (dd, J = 12.7, 8.1 z, 1), 1.51 (s, 1), (m, 1), (m, 2), 1.09 (s, 3), 0.99 (ddd, J = 13.9, 11.7, 8.1 z, 1), 0.91 (s, 3), 0.86 (t, J = 4.8 z, 1), 0.53 (dd, J = 8.1, 5.3 z, 1). 13 C NMR (151 Mz, Chloroform-d) δ 221.5, 134.6, 121.8, 82.8, 69.8, 59.4, 42.9, 38.4, 36.6, 34.3, 31.8, 28.8, 28.0, 26.1, 25.3, 17.6, 15.0, 7.3. RMS (ESI) m/z: Calculated for C O 3 [M+] , found MP: [α] D (c 1.0, CCl 3 ) TLC: R f 0.50 (1:1 hexanes:ethyl acetate, anisaldehyde [blue]). X-Ray: for coordinates see page SI-107 SI- 39

40 O O OEt, LaCl 3 Li O O O O 51%, 20% rsm O Compound 23 Experimental: In a flame-dried flask, ethyl vinyl ether (2.00 ml, 20.9 mmol, 56.3 equiv) was added to dry TF (8.00 ml) under Ar and chilled to -78 C. t-buli (4.00 ml, 1.7 M in pentanes, 6.80 mmol, 18.3 equiv) was then added dropwise. The now yellow solution was allowed to stir for 30 min at -78 C before allowing to warm to -20 C for a further 30 min, during which the yellow color turn pale. The vinyl lithium solution was then cooled to -78 C and a solution of LaCl 3 2LiCl (12.00 ml, 0.59 M in TF, 7.08 mmol, 19.1 equiv) added dropwise via syringe. The orange suspension was allowed to stir at -78 C for an additional 1 h. In a separate flame-dried flask, 22 (112 mg, mmol, 1.00 equiv) was dissolved in dry TF (3.00 ml) under Ar. The TF solution of 22 was then transferred via syringe to the stirring vinyl lanthanum solution. Additional TF (3.00 ml) was used to ensure complete transfer of the substrate. The reaction was then stirred under Ar in a dry ice/acetone bath for 12 h, during which the bath temperature rose from -78 C to -40 C. The reaction was then quenched by the addition of saturated aqueous ammonium chloride (15 ml) before allowing to warm to room temperature. The biphasic mixture was further diluted with more saturated ammonium chloride (50 ml) and EtOAc (5 ml). The layers were separated and the aqueous layer was further extracted with EtOAc (5 x 6 ml). The combined organic layers was first concentrated in vacuo to remove the volatiles and then taken up in TF (5 ml) and 1M Cl (5 ml). The biphasic mixture was stirred vigorously for 1 h before the layers were again separated and the aqueous layer was further extracted with EtOAc (5 x 6 ml). The combined organic layers were dried over magnesium sulfate, and then concentrated in vacuo to deliver the crude as a yellow gum. The crude mixture was then purified via flash chromatography on silica gel (3:1 hexanes:etoac to 6:4 hexanes:etoac) to give compound 23 (66 mg, mmol, 51%) as a white solid and recovered 22 (22 mg, mmol, 20%). Physical state: white solid 1 NMR (600 Mz, Chloroform-d) δ 5.70 (dd, J = 9.8, 1.7 z, 1), 5.30 (dd, J = 9.9, 2.6 z, 1), 4.29 (s, 1), (m, 1), 2.98 (s, 1), 2.77 (ddd, J = 14.5, 12.0, 5.1 z, 1), 2.34 (s, 3), 2.19 (dt, J = 10.5, 2.2 z, 1), (m, 2), (m, 2), (m, 4), (m, 2), 1.21 (dt, J = 8.6, 4.5 z, 1), 1.16 (s, 3), (m, 1), 0.89 (s, 3), 0.83 (t, J = 4.8 z, 1), 0.51 (dd, J = 8.1, 5.2 z, 1). 13 C NMR (151 Mz, Chloroform-d) δ 213.3, 133.7, 123.1, 91.8, 87.8, 70.4, 60.8, 42.7, 42.2, 38.2, 36.6, 32.9, 31.8, 31.7, 31.5, 28.4, 26.0, 25.3, 17.8, 14.9, 6.6. RMS (ESI) m/z: Calculated for C O 4 Na [M+Na] , found MP: 188 C (Decomposition) [α] D (c 0.45, CCl 3 ) TLC: R f 0.41 (1:1 hexanes:ethyl acetate, anisaldehyde [blue]). X-Ray: for coordinates see page SI-118 SI- 40

41 SI- 41

42 O O O 1. Br; Ag(TFA) 2. TFA/ 2 O O O O O 23 60% O O 2 pergularin Pergularin, Compound 2 Experimental: 23 (30 mg, mmol, 1.00 equiv) was first taken up in EtOAc (5.0 ml). Br (10 μl, 33% in AcO) was added and the reaction stirred for 15 min at room temperature. Then, DI 2 O (1.0 ml) followed by AgTFA (0.100 g, mmol, 5.22 equiv) was added. The flask was wrapped in foil and allowed to stir for 4 h in the dark at room temperature. Saturated sodium bicarbonate (3.0 ml) and brine (3.0 ml) were then added and the reaction mixture filtered over a pad of Celite. The layers were separated and the aqueous layer was further extracted with EtOAc (5 x 2.0 ml). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to deliver the crude as a yellow wax. The crude compound was submitted to the next reaction without further purification. The crude compound was first dissolved in TF (2.0 ml) followed by sequential addition of DI 2 O (1.0 ml) and trifluoroacetic acid (1.0 ml). The reaction mixture was then allowed to stir at room temperature for 12 h; afterwhich, the volatiles were remove in vacuo. The crude mixture was then purified via flash chromatography on silica gel (3:1 hexanes:etoac to EtOAc) to give pergularin 2 (19 mg, mmol, 60%) as a waxy solid. Physical state: waxy solid 1 NMR (600 Mz, thanol-d4) δ (m, 1), (m, 2), 2.94 (ddd, J = 15.0, 12.3, 4.1 z, 1), 2.28 (ddd, J = 13.0, 5.1, 2.2 z, 1), 2.23 (s, 3), (m, 2), (m, 2), (m, 3), (m, 2), 1.63 (dt, J = 12.8, 4.4 z, 1), (m, 1), 1.40 (q, J = 12.5 z, 1), (m, 1), 1.20 (s, 3), 1.11 (td, J = 13.7, 3.9 z, 1), 1.03 (s, 3). 13 C NMR (151 Mz, thanol-d4) δ 211.6, 141.2, 122.6, 93.0, 90.0, 72.4, 69.6, 59.9, 44.7, 43.0, 38.5, 38.0, 37.6, 32.8, 32.3, 32.0, 31.5, 27.7, 27.3, 20.1, 7.2. RMS (ESI) m/z: Calculated for C O 5 Na [M+Na] , found [α] D (c 1.0, O), reported [α] D (c 0.1, O) 11 TLC: R f 0.56 (ethyl acetate, anisaldehyde [blue]). SI- 42

43 Comparison Table: pergularin, 2 1 NMR (d 5 -pyridine) 13 C NMR (d 5 -pyridine) isolation 12 synthetic difference isolation synthetic difference n.r (1) n.r (1) n.r (1) n.r (1) (1) (1) (1) (3) n.r (1) n.r (1) n.r (1) (SQC) n.r (1) (SQC) n.r (8) (SQC) n.r (1) (SQC) , n.r (1) (SQC) (3) n.r (1) n.r (1) (3) n.r. not reported; difference in the observed chemical shift is due to different reference used (d 5 - pyridine vs TMS) SI- 43

44 O O O NaB 4, 0 C O O O O O 2 pergularin 75% O O 1 utendin Utendin, Compound 1 Experimental: Pergularin 2 (10 mg, mmol) was first taken up in dry O (3.0 ml) under Ar and cooled to -15 C. Sodium borohydride (30 mg, mmol, 28.9 equiv) was added in one portion with stirring. The reaction was allowed to warm to 0 C over the course of 2 h, during which TLC analysis showed the full comsumption of the starting material. The reaction was then quenched by the slow additon of 1M Cl (1.0 ml). The reaction mixture was then diluted with EtOAc (2.0 ml) and the layers separated. The aqueous layer was further extracted with EtOAc (5 x 2.0 ml). The combined organic layers were dried over magnesium sulfate, and then concentrated in vacuo. The crude mixture was either taken onto the next step towards tomentogenin or it was purified via flash chromatography on silica gel (3:1 hexanes:etoac to EtOAc) to give utendin 1 (7.5 mg, mmol, 75%, inseparable mixture of diastereomers 5:1) as a white waxy solid. Physical state: white waxy solid 1 NMR (600 Mz, thanol-d4) δ 5.40 (dt, J = 4.7, 2.1 z, 1), 3.96 (q, J = 6.5 z, 1), 3.52 (dd, J = 11.6, 4.6 z, 1), (m, 1), 2.28 (ddd, J = 13.2, 5.1, 2.2 z, 1), (m, 1), (m, 1), (m, 2), (m, 7), (m, 2), (m, 1), 1.18 (d, J = 6.5 z, 3), 1.14 (s, 3), (m, 1), 1.04 (s, 3). 13 C NMR (151 Mz, thanol-d4) δ 141.1, 122.7, 89.7, 89.6, 73.7, 72.4, 71.1, 57.9, 44.3, 42.9, 38.5, 37.9, 37.2, 34.8, 32.3, 32.1, 31.6, 27.3, 20.1, 17.0, 8.7. RMS (ESI) m/z: Calculated for C O 5 Na [M+Na] , found [α] D (c 0.1, O), reported [α] D (c 1.1, O) 13 TLC: R f 0.32 (ethyl acetate, anisaldehyde [blue]). SI- 44

45 Comparison Table: utendin, 1 1 NMR (d 5 -pyridine) 13 C NMR (d 5 -pyridine) isolation 14 synthetic difference isolation synthetic difference (1) 0.14 n.r (1) 0.32 n.r (1) 0.26 n.r (1) 0.28 n.r n.r (1) (SQC) - n.r n.r (1) (SQC) - n.r n.r (1) (SQC) - n.r n.r (1) (SQC) - n.r n.r (10) - n.r (3) 0.39 n.r (3) 0.26 n.r n.r (1) - n.r n.r (1) - n.r (3) 0.26 n.r n.r n.r n.r n.r n.r n.r n.r. not reported; difference in the observed chemical shift is due to different reference used (d 5 - pyridine vs TMS) SI- 45

46 O O O NaB 4, 0 C O O O Pd/C, 2 O O O O O 2 pergularin 75% O O 1 utendin 80% O O 3 tomentogenin Tomentogenin, Compound 3 Experimental: The resulting crude product 1 of the sodium borohydride reduction of pergularin 2 (6.6 mg, mmol) was taken up in O (2.0 ml) under Ar. Pd/C (1.5 mg, 5 wt%) was added and the atmosphere exchanged with 2 via sparging using a needle and balloon for 30 min. The reaction mixture was stirred vigorously for 24 h. After which, the reaction was filtered over a pad of Celite and purified via flash chromatography on silica gel (3:1 hexanes:etoac to EtOAc) to give tomentogenin 3 (4.8 mg, mmol, 60%, 2 steps, inseparable mixture of diastereomers 5:1) as a white waxy solid. Physical state: white waxy solid 1 NMR (600 Mz, thanol-d4) δ 3.94 (q, J = 6.4 z, 1), (m, 1), 3.46 (dd, J = 11.5, 4.6 z, 1), 1.94 (dq, J = 12.9, 3.4 z, 1), (m, 2), (m, 4), (m, 2), (m, 1), (m, 5), 1.17 (d, J = 6.5 z, 3), (m, 1), 1.11 (s, 3), (m, 2), (m, 1), 0.85 (s, 3). 13 C NMR (151 Mz, thanol-d4) δ 89.4 (2C), 73.7, 71.9, 71.4, 58.2, 47.3, 46.0, 40.8, 38.9, 38.4, 36.8, 35.1, 32.2, 31.7, 31.5, 29.8, 27.9, 17.0, 12.8, 8.9. RMS (ESI) m/z: Calculated for C O 5 Na [M+Na] , found [α] D (c 0.2, O), reported [α] D (c 0.95, O) 15 TLC: R f 0.31 (ethyl acetate, anisaldehyde [blue]). X-Ray: for coordinates see page SI-128 SI- 46

47 Comparison Table: tomentogenin, 3 1 NMR (d 5 -pyridine) 13 C NMR (d 5 -pyridine) isolation 16 synthetic difference isolation synthetic difference n.r n.r n.r n.r (2C) n.r n.r n.r n.r n.r n.r n.r n.r n.r n.r n.r n.r n.r n.r n.r n.r n.r. not reported; difference in the observed chemical shift is due to different reference used (d 5 - pyridine vs TMS) SI- 47

48 Compound 5 Table 1. Crystal data and structure refinement for baran517_a. Identification code baran517_a Empirical formula C19 26 O Formula weight Temperature K Wavelength Å Crystal system Monoclinic Space group P Unit cell dimensions a = (3) Å a= 90. b = (10) Å b= (2). c = (6) Å g = 90. Volume (6) Å 3 Z 4 Density (calculated) Mg/m 3 Absorption coefficient mm -1 F(000) 592 Crystal size 0.3 x 0.2 x 0.1 mm 3 Theta range for data collection to Index ranges -12<=h<=12, -7<=k<=7, -26<=l<=27 Reflections collected Independent reflections 5347 [R(int) = ] Completeness to theta = % Absorption correction Semi-empirical from equivalents Max. and min. transmission and Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 5347 / 1 / 365 Goodness-of-fit on F Final R indices [I>2sigma(I)] R1 = , wr2 = SI- 48

49 R indices (all data) R1 = , wr2 = Absolute structure parameter 0.04(9) Extinction coefficient n/a Largest diff. peak and hole and e.å -3 Table 2. Atomic coordinates ( x 10 4 ) and equivalent isotropic displacement parameters (Å 2 x 10 3 ) for baran517_a. U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. x y z U(eq) O(1) 4783(1) 6129(3) 994(1) 42(1) O(2) 595(2) 10567(3) 4191(1) 48(1) C(35) 1492(2) 3545(4) 1908(1) 34(1) C(20) 4221(2) 4424(4) 891(1) 35(1) C(32) -537(2) 1321(4) 1660(1) 34(1) C(7) 6333(2) 4886(4) 4256(1) 38(1) C(1) 1200(2) 8875(4) 4221(1) 37(1) C(37) 3303(2) 3300(3) 1270(1) 32(1) C(25) 583(2) -389(4) 632(1) 37(1) C(34) 633(2) 2463(4) 1435(1) 31(1) C(3) 2347(2) 5664(4) 4629(1) 37(1) C(23) 2408(2) 2252(4) 803(1) 31(1) C(16) 3893(2) 9066(4) 3163(1) 34(1) C(15) 4838(2) 7880(4) 3582(1) 31(1) C(18) 2160(2) 8135(4) 3801(1) 33(1) C(24) 1394(2) 861(4) 1067(1) 31(1) C(4) 3129(2) 7072(4) 4230(1) 32(1) C(11) 7666(2) 9753(4) 3504(1) 42(1) C(8) 6889(2) 6098(4) 3782(1) 34(1) C(5) 4196(2) 6018(4) 3919(1) 31(1) C(26) -642(2) -537(4) 663(1) 38(1) C(27) -1315(2) 504(4) 1129(1) 36(1) C(17) 2766(2) 9984(4) 3468(1) 35(1) C(6) 5115(2) 4827(4) 4320(1) 37(1) C(13) 6006(2) 6981(4) 3294(1) 33(1) C(36) 2575(2) 4818(4) 1654(1) 34(1) SI- 49

50 C(12) 6773(2) 8850(4) 3022(1) 38(1) C(19) 1489(2) 6441(4) 3392(1) 37(1) C(22) 3280(2) 1232(4) 374(1) 35(1) C(29) -2658(2) -115(4) 1213(1) 40(1) C(10) 8210(2) 5596(4) 3632(1) 38(1) C(14) 5667(2) 5191(4) 2844(1) 38(1) C(9) 7927(2) 7792(4) 3899(1) 38(1) C(21) 4291(2) 3033(4) 345(1) 41(1) C(33) -185(2) -578(4) 2078(1) 38(1) C(38) 4075(2) 1567(4) 1630(1) 36(1) C(28) -2360(2) 2183(4) 999(1) 42(1) C(31) -1409(2) 3019(4) 1937(1) 39(1) C(2) 1175(2) 7112(5) 4692(1) 41(1) C(30) -2217(2) 4034(4) 1436(1) 45(1) Table 3. Bond lengths [Å] and angles [ ] for baran517_a. O(1)-C(20) 1.207(3) O(2)-C(1) 1.207(3) C(35)-(35A) C(35)-(35B) C(35)-C(34) 1.537(3) C(35)-C(36) 1.539(3) C(20)-C(37) 1.519(3) C(20)-C(21) 1.523(3) C(32)-C(34) 1.551(3) C(32)-C(27) 1.529(3) C(32)-C(33) 1.531(3) C(32)-C(31) 1.551(3) C(7)-(7) C(7)-C(8) 1.476(3) C(7)-C(6) 1.328(3) C(1)-C(18) 1.527(3) C(1)-C(2) 1.524(4) C(37)-C(23) 1.542(3) SI- 50

51 C(37)-C(36) 1.524(3) C(37)-C(38) 1.547(3) C(25)-(25) C(25)-C(24) 1.498(3) C(25)-C(26) 1.328(3) C(34)-(34) C(34)-C(24) 1.552(3) C(3)-(3A) C(3)-(3B) C(3)-C(4) 1.539(3) C(3)-C(2) 1.547(3) C(23)-(23) C(23)-C(24) 1.530(3) C(23)-C(22) 1.536(3) C(16)-(16A) C(16)-(16B) C(16)-C(15) 1.541(3) C(16)-C(17) 1.541(3) C(15)-(15) C(15)-C(5) 1.551(3) C(15)-C(13) 1.554(3) C(18)-C(4) 1.538(3) C(18)-C(17) 1.522(3) C(18)-C(19) 1.544(3) C(24)-(24) C(4)-(4) C(4)-C(5) 1.529(3) C(11)-(11A) C(11)-(11B) C(11)-C(12) 1.531(3) C(11)-C(9) 1.509(4) C(8)-C(13) 1.531(3) C(8)-C(10) 1.514(3) C(8)-C(9) 1.524(3) C(5)-(5) C(5)-C(6) 1.500(3) SI- 51

52 C(26)-(26) C(26)-C(27) 1.475(3) C(27)-C(29) 1.516(3) C(27)-C(28) 1.528(3) C(17)-(17A) C(17)-(17B) C(6)-(6) C(13)-C(12) 1.549(3) C(13)-C(14) 1.529(3) C(36)-(36A) C(36)-(36B) C(12)-(12A) C(12)-(12B) C(19)-(19A) C(19)-(19B) C(19)-(19C) C(22)-(22A) C(22)-(22B) C(22)-C(21) 1.539(3) C(29)-(29A) C(29)-(29B) C(29)-C(28) 1.508(3) C(10)-(10A) C(10)-(10B) C(10)-C(9) 1.497(3) C(14)-(14A) C(14)-(14B) C(14)-(14C) C(9)-(9) C(21)-(21A) C(21)-(21B) C(33)-(33A) C(33)-(33B) C(33)-(33C) C(38)-(38A) C(38)-(38B) SI- 52

53 C(38)-(38C) C(28)-(28) C(28)-C(30) 1.507(4) C(31)-(31A) C(31)-(31B) C(31)-C(30) 1.537(3) C(2)-(2A) C(2)-(2B) C(30)-(30A) C(30)-(30B) (35A)-C(35)-(35B) C(34)-C(35)-(35A) C(34)-C(35)-(35B) C(34)-C(35)-C(36) (17) C(36)-C(35)-(35A) C(36)-C(35)-(35B) O(1)-C(20)-C(37) 126.7(2) O(1)-C(20)-C(21) 125.6(2) C(37)-C(20)-C(21) (18) C(34)-C(32)-C(31) (18) C(27)-C(32)-C(34) (17) C(27)-C(32)-C(33) (19) C(27)-C(32)-C(31) (17) C(33)-C(32)-C(34) (17) C(33)-C(32)-C(31) (18) C(8)-C(7)-(7) C(6)-C(7)-(7) C(6)-C(7)-C(8) 122.7(2) O(2)-C(1)-C(18) 126.2(2) O(2)-C(1)-C(2) 126.5(2) C(2)-C(1)-C(18) (19) C(20)-C(37)-C(23) (17) C(20)-C(37)-C(36) (18) C(20)-C(37)-C(38) (17) C(23)-C(37)-C(38) (17) SI- 53

54 C(36)-C(37)-C(23) (17) C(36)-C(37)-C(38) (18) C(24)-C(25)-(25) C(26)-C(25)-(25) C(26)-C(25)-C(24) 122.6(2) C(35)-C(34)-C(32) (17) C(35)-C(34)-(34) C(35)-C(34)-C(24) (16) C(32)-C(34)-(34) C(32)-C(34)-C(24) (17) C(24)-C(34)-(34) (3A)-C(3)-(3B) C(4)-C(3)-(3A) C(4)-C(3)-(3B) C(4)-C(3)-C(2) (19) C(2)-C(3)-(3A) C(2)-C(3)-(3B) C(37)-C(23)-(23) C(24)-C(23)-C(37) (17) C(24)-C(23)-(23) C(24)-C(23)-C(22) (18) C(22)-C(23)-C(37) (17) C(22)-C(23)-(23) (16A)-C(16)-(16B) C(15)-C(16)-(16A) C(15)-C(16)-(16B) C(15)-C(16)-C(17) (17) C(17)-C(16)-(16A) C(17)-C(16)-(16B) C(16)-C(15)-(15) C(16)-C(15)-C(5) (16) C(16)-C(15)-C(13) (17) C(5)-C(15)-(15) C(5)-C(15)-C(13) (17) C(13)-C(15)-(15) C(1)-C(18)-C(4) 99.57(17) SI- 54

55 C(1)-C(18)-C(19) (17) C(4)-C(18)-C(19) (18) C(17)-C(18)-C(1) (19) C(17)-C(18)-C(4) (17) C(17)-C(18)-C(19) (18) C(25)-C(24)-C(34) (17) C(25)-C(24)-C(23) (17) C(25)-C(24)-(24) C(34)-C(24)-(24) C(23)-C(24)-C(34) (17) C(23)-C(24)-(24) C(3)-C(4)-(4) C(18)-C(4)-C(3) (17) C(18)-C(4)-(4) C(5)-C(4)-C(3) (19) C(5)-C(4)-C(18) (17) C(5)-C(4)-(4) (11A)-C(11)-(11B) C(12)-C(11)-(11A) C(12)-C(11)-(11B) C(9)-C(11)-(11A) C(9)-C(11)-(11B) C(9)-C(11)-C(12) (19) C(7)-C(8)-C(13) (18) C(7)-C(8)-C(10) 120.0(2) C(7)-C(8)-C(9) 121.4(2) C(10)-C(8)-C(13) (18) C(10)-C(8)-C(9) 59.06(15) C(9)-C(8)-C(13) (19) C(15)-C(5)-(5) C(4)-C(5)-C(15) (17) C(4)-C(5)-(5) C(6)-C(5)-C(15) (17) C(6)-C(5)-C(4) (17) C(6)-C(5)-(5) C(25)-C(26)-(26) SI- 55

56 C(25)-C(26)-C(27) 122.9(2) C(27)-C(26)-(26) C(26)-C(27)-C(32) (18) C(26)-C(27)-C(29) 120.1(2) C(26)-C(27)-C(28) 121.5(2) C(29)-C(27)-C(32) (19) C(29)-C(27)-C(28) 59.40(15) C(28)-C(27)-C(32) 108.0(2) C(16)-C(17)-(17A) C(16)-C(17)-(17B) C(18)-C(17)-C(16) (17) C(18)-C(17)-(17A) C(18)-C(17)-(17B) (17A)-C(17)-(17B) C(7)-C(6)-C(5) 122.6(2) C(7)-C(6)-(6) C(5)-C(6)-(6) C(8)-C(13)-C(15) (16) C(8)-C(13)-C(12) (17) C(12)-C(13)-C(15) (18) C(14)-C(13)-C(15) (17) C(14)-C(13)-C(8) (18) C(14)-C(13)-C(12) (18) C(35)-C(36)-(36A) C(35)-C(36)-(36B) C(37)-C(36)-C(35) (18) C(37)-C(36)-(36A) C(37)-C(36)-(36B) (36A)-C(36)-(36B) C(11)-C(12)-C(13) (19) C(11)-C(12)-(12A) C(11)-C(12)-(12B) C(13)-C(12)-(12A) C(13)-C(12)-(12B) (12A)-C(12)-(12B) C(18)-C(19)-(19A) SI- 56

57 C(18)-C(19)-(19B) C(18)-C(19)-(19C) (19A)-C(19)-(19B) (19A)-C(19)-(19C) (19B)-C(19)-(19C) C(23)-C(22)-(22A) C(23)-C(22)-(22B) C(23)-C(22)-C(21) (17) (22A)-C(22)-(22B) C(21)-C(22)-(22A) C(21)-C(22)-(22B) C(27)-C(29)-(29A) C(27)-C(29)-(29B) (29A)-C(29)-(29B) C(28)-C(29)-C(27) 60.71(15) C(28)-C(29)-(29A) C(28)-C(29)-(29B) C(8)-C(10)-(10A) C(8)-C(10)-(10B) (10A)-C(10)-(10B) C(9)-C(10)-C(8) 60.80(15) C(9)-C(10)-(10A) C(9)-C(10)-(10B) C(13)-C(14)-(14A) C(13)-C(14)-(14B) C(13)-C(14)-(14C) (14A)-C(14)-(14B) (14A)-C(14)-(14C) (14B)-C(14)-(14C) C(11)-C(9)-C(8) (19) C(11)-C(9)-(9) C(8)-C(9)-(9) C(10)-C(9)-C(11) 118.2(2) C(10)-C(9)-C(8) 60.13(15) C(10)-C(9)-(9) C(20)-C(21)-C(22) (18) SI- 57

58 C(20)-C(21)-(21A) C(20)-C(21)-(21B) C(22)-C(21)-(21A) C(22)-C(21)-(21B) (21A)-C(21)-(21B) C(32)-C(33)-(33A) C(32)-C(33)-(33B) C(32)-C(33)-(33C) (33A)-C(33)-(33B) (33A)-C(33)-(33C) (33B)-C(33)-(33C) C(37)-C(38)-(38A) C(37)-C(38)-(38B) C(37)-C(38)-(38C) (38A)-C(38)-(38B) (38A)-C(38)-(38C) (38B)-C(38)-(38C) C(27)-C(28)-(28) C(29)-C(28)-C(27) 59.89(15) C(29)-C(28)-(28) C(30)-C(28)-C(27) (19) C(30)-C(28)-C(29) 118.1(2) C(30)-C(28)-(28) C(32)-C(31)-(31A) C(32)-C(31)-(31B) (31A)-C(31)-(31B) C(30)-C(31)-C(32) (19) C(30)-C(31)-(31A) C(30)-C(31)-(31B) C(1)-C(2)-C(3) (18) C(1)-C(2)-(2A) C(1)-C(2)-(2B) C(3)-C(2)-(2A) C(3)-C(2)-(2B) (2A)-C(2)-(2B) C(28)-C(30)-C(31) 104.3(2) SI- 58

59 C(28)-C(30)-(30A) C(28)-C(30)-(30B) C(31)-C(30)-(30A) C(31)-C(30)-(30B) (30A)-C(30)-(30B) Symmetry transformations used to generate equivalent atoms: Table 4. Anisotropic displacement parameters (Å 2 x 10 3 ) for baran517_a. The anisotropic displacement factor exponent takes the form: -2p 2 [ h 2 a* 2 U h k a* b* U 12 ] U 11 U 22 U 33 U 23 U 13 U 12 O(1) 37(1) 37(1) 53(1) 0(1) 3(1) -6(1) O(2) 39(1) 44(1) 62(1) -9(1) 12(1) 1(1) C(35) 33(1) 35(1) 33(1) -4(1) 4(1) 3(1) C(20) 28(1) 35(1) 42(1) 3(1) -1(1) 3(1) C(32) 32(1) 34(1) 36(1) 2(1) 4(1) 1(1) C(7) 35(1) 40(1) 37(1) 4(1) 1(1) 4(1) C(1) 28(1) 41(1) 42(1) -9(1) 3(1) -6(1) C(37) 30(1) 28(1) 36(1) -1(1) 0(1) 0(1) C(25) 40(1) 35(1) 34(1) -3(1) 6(1) -4(1) C(34) 31(1) 31(1) 32(1) 1(1) 3(1) 1(1) C(3) 34(1) 45(1) 33(1) 1(1) 5(1) -7(1) C(23) 32(1) 28(1) 33(1) 0(1) 1(1) 1(1) C(16) 34(1) 33(1) 35(1) 4(1) 6(1) -3(1) C(15) 31(1) 29(1) 33(1) -2(1) 4(1) -3(1) C(18) 29(1) 34(1) 36(1) -1(1) 3(1) -2(1) C(24) 31(1) 30(1) 33(1) 0(1) 2(1) 1(1) C(4) 30(1) 34(1) 32(1) -2(1) 3(1) -4(1) C(11) 35(1) 36(1) 56(1) -5(1) 12(1) -5(1) C(8) 29(1) 35(1) 38(1) -4(1) 4(1) -1(1) C(5) 30(1) 32(1) 32(1) 1(1) 3(1) -3(1) C(26) 39(1) 40(1) 34(1) 0(1) -2(1) -10(1) C(27) 31(1) 36(1) 39(1) 6(1) 1(1) -1(1) C(17) 34(1) 32(1) 40(1) 2(1) 2(1) 2(1) SI- 59

60 C(6) 37(1) 38(1) 38(1) 6(1) 7(1) 1(1) C(13) 32(1) 32(1) 35(1) 0(1) 6(1) -1(1) C(36) 33(1) 32(1) 37(1) -5(1) 0(1) -1(1) C(12) 34(1) 39(1) 43(1) 3(1) 11(1) 0(1) C(19) 33(1) 40(1) 36(1) -2(1) 0(1) -2(1) C(22) 34(1) 36(1) 36(1) -2(1) 5(1) -1(1) C(29) 30(1) 42(1) 49(1) 7(1) 0(1) -3(1) C(10) 29(1) 41(1) 42(1) -4(1) 3(1) -2(1) C(14) 34(1) 43(1) 37(1) -6(1) 4(1) 1(1) C(9) 29(1) 43(1) 43(1) -9(1) 4(1) -2(1) C(21) 38(1) 43(1) 43(1) -2(1) 8(1) -4(1) C(33) 35(1) 40(1) 39(1) 5(1) 5(1) -1(1) C(38) 34(1) 36(1) 37(1) 0(1) -2(1) 1(1) C(28) 33(1) 44(1) 50(1) 10(1) -2(1) -2(1) C(31) 34(1) 39(1) 46(1) -1(1) 9(1) 0(1) C(2) 31(1) 57(2) 36(1) -3(1) 6(1) -8(1) C(30) 34(1) 38(1) 63(2) 6(1) 5(1) 4(1) Table 5. ydrogen coordinates ( x 10 4 ) and isotropic displacement parameters (Å 2 x 10 3 ) for baran517_a. x y z U(eq) (35A) (35B) (7) (25) (34) (3A) (3B) (23) (16A) (16B) (15) SI- 60

61 (24) (4) (11A) (11B) (5) (26) (17A) (17B) (6) (36A) (36B) (12A) (12B) (19A) (19B) (19C) (22A) (22B) (29A) (29B) (10A) (10B) (14A) (14B) (14C) (9) (21A) (21B) (33A) (33B) (33C) (38A) (38B) (38C) (28) (31A) SI- 61

62 (31B) (2A) (2B) (30A) (30B) SI- 62

63 Compound 12 Table 1. Crystal data and structure refinement for Baran490. Report date Identification code Empirical formula Molecular formula YYSEE03102 C19 26 O2 C19 26 O2 Formula weight Temperature Wavelength Crystal system K Å Monoclinic Space group P Unit cell dimensions a = (5) Å α= 90. b = (3) Å β= (10). c = (6) Å γ = 90. Volume (6) Å 3 Z 2 Density (calculated) Mg/m 3 Absorption coefficient mm -1 F(000) 312 SI- 63