Efficient anodic and direct phenol-arene C,C cross-coupling the benign role of water or methanol

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1 Efficient anodic and direct phenol-arene C,C cross-coupling the benign role of water or methanol Axel Kirste 2, Bernd Elsler 1, Gregor Schnakenburg 3, Siegfried R. Waldvogel 1 * 1 Institute for Organic Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, Mainz, Germany; 2 Kekulé Institute for Organic Chemistry and Biochemistry, Bonn University, Gerhard- Domagk-Strasse 1, Bonn, Germany; 3 X-ray Analysis Department, Institute for Inorganic Chemistry, Bonn University, Gerhard-Domagk-Strasse 1, Bonn, Germany waldvogel@uni-mainz.de Supporting Information Table of contents pg General information Further results Synthesis of substrates Electrochemical protocol Analytical data NMR spectra References S1 S2 S3 S5 S6 S21 S45 General information: All reagents were used in analytical grades. Solvents were desiccated if necessary by standard methods. N-Methyl-N,N,N-triethylammonium methylsulfate (MTES) was used as supporting electrolyte, which was provided by the BASF SE. For electrochemical reactions a BDD anode and a nickel cathode were applied. BDD electrodes were obtained from CONDIAS GmbH, Itzehoe, Germany. BDD (15 µm diamond layer) on 6 mm silicon support (wafer) was used. The current quotation for best coating quality coated on both sides is about ,- per square meters. This prize might tremendously erode in near future since the patents will run out and large capacities for BDD production are currently established in Asia. Column chromatography was performed on silica gel (particle size μm and μm for flash chromatography, Merck, Darmstadt, Germany) by using mixtures of cyclohexane with ethyl acetate as eluents. For thin-layer chromatography silica gel 60 sheets on glass (F254, Merck, Darmstadt, Germany) were used. Gas chromatography was performed with a Shimadzu GC-2010 (Shimadzu, Japan) using a HP 5 column (Agilent Technologies, USA; length: 30 m, inner diameter: 0.25 mm, film: 0.25 mm, carrier gas: hydrogen). GC-MS measurements were carried out with a Shimadzu GC-2010 (Shimadzu, Japan) using a HP 1 column (Agilent Technologies, USA; length: 30 m, inner diameter: 0.25 mm, film: 0.25 mm, carrier gas: hydrogen) combined with a GCMS-QP2010. Melting points were determined S1

2 with a Melting Point Apparatus B-545 (Büchi, Flawil, Switzerland) and were uncorrected. Microanalysis was performed with a VarioMICRO cube (Elementaranalysensysteme, Hanau, Germany). Spectroscopy and Spectrometry: 1 H NMR and 13 C NMR spectra were recorded at 25 C by using a Bruker AC 300 or AV II 400 instruments (Analytische Messtechnik, Karlsruhe, Germany). Chemical shifts (d) are reported in parts per million (ppm) relative to TMS as internal standard or traces of CHCl 3 in the corresponding deuterated solvent. Mass spectra and high resolution mass spectra were obtained by using a QTof Ultima 3 (waters, Milford, Massachusetts) apparatus employing ESI X-ray analysis: All data were collected on a Nonius KappaCCD diffractometer at 123 K (Oxford Cryostream 600er series, Oxford Cryosystems, 7ab, 14ab, 16d, 18ab, and 19ab) or a STOE IPDS2T diffractometer at 123 K (Oxford Cryostream 700er series, Oxford Cryosystems, 15ab) using graphite monochromated Mo K radiation ( = Å). Intensities were measured using fine-slicing and -scans and corrected for background, polarization and Lorentz effects. Semi-empirical absorption corrections from equivalent reflections according to Blessing s method 1 (7ab, 14ab, 16d, 18ab, and 19ab) or a numerical absorption correction from face indices (15ab) were applied for the data sets. The structures were solved by direct methods and refined anisotropically by the least-squares procedure implemented in the SHELX program system. 2 The supplementary crystallographic data for this paper can be obtained free of charge from The Cambridge Crystallographic Data Center via Deposition numbers and further details are given below. Further Results: Table 4. Electrochemical phenol-arene cross-coupling reaction: variation of anode material 3 Entry Anode material Isolated yield of 1ab (%) a CE (%) b Selectivity ab : bb 1 BDD >100 : 1 c 2 graphite : 1 3 glassy carbon : 1 4 platinum >100 : 1 c a Electrolysis conditions: 50 C, constant current (j=2.8 ma/cm 2 ), undivided cell, 2 F/mol phenol, ratio phenol/arene = 1:3, 0.68 g Et 3 NMe O 3 SOMe, 27 ml (F 3 C) 2 CHOH (HFIP), 6 ml MeOH. b Current efficiency. c 1bb was not detected using GC. S2

3 Table 5. Comparison of conditions a entry phenol + aren components isolated cross-coupling product yield (%) CE d (%) selectivity AB : BB 1 42 a (33) b 42 (33) >100 : 1 c (12 : 1) 2 12 a (11) b 12 (11) >100 : 1 c (2.5 1) 3 11 a (15) b 11 (15) 4.5 : 1 (1 : 1) 4 17 a (5) b 17 (5) 1 : 1.5 (1 : 13) a Electrolysis conditions: 50 C, BDD anode, constant current (j=2.8 ma/cm 2 ), undivided cell, 2 F/mol phenol, ratio phenol/arene = 1:3, 0.68 g Et 3 NMe O 3 SOMe, 27 ml HFIP, 6 ml MeOH. b Non-optimized electrolysis conditions in pure HFIP; ratio phenol/arene = 1:10, values are taken from the reference 3. c bb was not detected using GC. d Current efficiency. Synthesis of substrates: All substrates were used from commercial sources, except the ones which are listed below. 2,4-Dimethoxyphenol (4a) 4 : A solution of 2,4- dimethoxybenzaldehyde (3.32 g, 0.02 mol) in methanol (30 ml) was prepared. At 0 C (ice bath conditions) H 2 O 2 (30%, 2.60 g, 0.02 mol) and H 2 SO 4 (98%, 0.4 ml) are added drop wise while vigorous stirring. Then, the solution was stirred for additional 24 hours at room temperature. Subsequently, the mixture was given on ice water (100 ml) and stirred for 5 minutes. The aqueous mixture was extracted with CH 2 Cl 2 (3 50 ml). The combined organic fractions are dried over Na 2 SO 4 and concentrated under reduced pressure. The remaining dark yellow liquid was purified by column chromatography on silica using a mixture of cyclohexane/ethyl acetate (2:1). After drying in vacuum ( mbar) a slightly yellow liquid S3

4 was obtained (2.67 g, mol, 87%). R f (cyclohexane/ethyl acetate = 2:1): 0.23; 1 H NMR (300 MHz, CDCl 3 ) δ = 6.82 (d, J = 8.6 Hz, 1H), 6.49 (d, J = 2.8 Hz, 1H), 6.39 (dd, J = 8.6 Hz, 2.8 Hz, 1H), 4.97 (s, 1H), 3.85 (s, 3H), 3.76 (s, 3H). 2-Hydroxy-3-methoxynaphthalene (10a) 5 : A solution of 2,3-dihydroxynaphthalene (8.01 g, 0.05 mol) in methoxy ethanol (50 ml) was prepared. At ambient temperature KOt-Bu (5.61 g, 0.05 mol) and dimethyl sulfate (6.31 g, 0.05 mol) were added in small portions while vigorous stirring. The reaction mixture was stirred at 80 C overnight. Subsequently, NaOH (15 ml, 40% in water) and water (25 ml) were added at 80 C and the solution was warmed up to room temperature. The solvent was removed under reduced pressure, the precipitate treated with hydrochloric acid (50 ml, 10%) and methylene chloride was added (20 ml). After phase separation the aqueous layer was extracted with methylene chloride (3 50 ml). The combined organic fractions were washed with water, dried over MgSO 4 and concentrated under reduced pressure. The remaining brown highly viscous liquid was purified by column chromatography in cyclohexane/ethyl acetate (85:15). After drying in vacuo a slightly yellow solid was obtained (4.55 g, mol, 52%). Mp: C, R f (cyclohexane/ethyl acetate = 85:15): 0.24; 1 H NMR (300 MHz, CDCl 3 ) δ = (m, 2H), (m, 2H), 7.41 (s, 1H), 6.09 (s, 1H), 4.15 (s, 3H). 1,2-Dimethoxy-4-methylbenzene (2b): A solution of 4- methylcatechol (12.4 g, 0.10 mol) and sodium hydroxide (10.0 g, 0.25 mol) in water (50 ml) was prepared. At 0 C (ice bath conditions) dimethyl sulfate (76.0 g, 0.6 mol, 57 ml) was added drop wise within 30 minutes while vigorous stirring. Then, the solution was stirred overnight at room temperature. Subsequently, 100 ml tert-butyl methyl ether was added and the phases were separated. The aqueous layer was extracted by tert-butyl methyl ether (3 50 ml). The combined organic fractions were washed with aqueous sodium hydroxide solution (10%, 2 30 ml), dried over MgSO 4 and concentrated under reduced pressure. The remaining yellow liquid was purified by distillation under reduced pressure (95 C, 10 mbar). A colorless liquid was obtained (7.87 g, mol, 52%). 1 H NMR (500 MHz, CDCl 3 ) δ = 6.69 (d, J = 8.6 Hz, 1H), (m, 2H), 3.79 (s, 3H), 3.77 (s, 3H), 2.23 (s, 3H). 1,3-Dimethoxy-5-methylbenzene (3b) 6 : A solution of orcinol (35.5 g, 0.29 mol) and potassium carbonate (70.1 g, 0.51 mol) in acetone (450 ml) was prepared. At 0 C (ice bath conditions) dimethyl sulfate (73.3 g, 0.59 mol, 55 ml) was added drop wise within 60 minutes while vigorous stirring. Then, the solution was heated to reflux for 24 hours. After completion of the reaction, the mixture was chilled to room S4

5 temperature and the solvent removed under reduced pressure. Subsequently, the mixture was fractionized with 100 ml tert-butyl methyl ether and 400 ml water. The aqueous layer was extracted by tert-butyl methyl ether (3 100 ml). The combined organic fractions were washed with aqueous sodium hydroxide solution (10%, 2 50 ml), dried over MgSO 4 and concentrated under reduced pressure. The remaining yellow liquid was purified by distillation under reduced pressure ( C steam temperature, 18 mbar). A slightly yellow liquid was obtained (27.0 g, 0.18 mol, 62%). 1 H NMR (400 MHz, CDCl 3 ) δ = 6.33 (d, J = 2.2 Hz, 2H), 6.28 (d, J = 2.2 Hz, 1H), 3.76 (s, 3H), 2.29 (s, 3H). 2,3-Dimethoxynaphthalene (6b) 7 : A solution of 2,3- dihydroxynaphthalene (20.4 g, 0.13 mol) and potassium carbonate (40.0 g, 0.29 mol) in acetone (300 ml) and water (20 ml) was prepared. At 0 C (ice bath conditions) dimethyl sulfate (37.1 g, mol, 28 ml) was added drop wise within 30 minutes while stirring vigorously. Then, the solution was heated to reflux overnight. After completion of the reaction, the mixture was chilled to room temperature and the solvent removed under reduced pressure. The residue solid was dissolved in CH 2 Cl 2 (100 ml) and washed with water (2 50 ml), dried over MgSO 4 and concentrated under reduced pressure. An off-white solid was obtained (21.5 g, 0.11 mol, 90%). 1 H NMR (300 MHz, CDCl 3 ) δ = (m, 2H), (m, 2H), 7.13 (s, 2H), 4.01 (s, 6H). Electrochemical protocol: General procedure for the anodic phenol-arene cross-coupling reaction: A solution of phenol component (0.005 mol), arene component (0.015 mol) and N-methyl-N,N,Ntriethylammonium methylsulfate (0.68 g, mol) in 1,1,1,3,3,3-hexafluoropropan-2-ol (27 ml) and methanol (6 ml) was transferred into a undivided electrolysis cell equipped with a BDD anode and a nickel cathode. At 50 C, a constant current electrolysis with a current density of 2.8 ma/cm 2 was performed. After 965 C (2 F per mol phenol) the electrolysis was stopped and the solvent mixture was recovered in vacuo (50 C, 150 mbar). Non-converted starting materials were recovered by short-path-distillation ( C, 10-3 mbar) and purification of the crude products by column chromatography (SiO 2, ethyl acetate/ cyclohexane) provided the coupling products. They were washed with cold n-heptane (0 C) and drying in high vacuum yielded the corresponding non-symmetrical biaryls as almost colorless solids. S5

6 Figure 2 Design of electrolysis cell equipped with BDD anode; 8 EPDM: ethylene propylene diene monomer rubber. General procedure for derivatisation of the crude products: After electrolysis, removal of the solvents and recovering of non-converted starting materials the crude product was directly subjected to a standard derivatisation protocol. Propionic anhydride (3 g, 5 eq.), N,N-4-(dimethylamino)pyridine (0.25 g, 0.5 eq.) and pyridine (5.2 g, 15 eq.) were added. The mixture was stirred for 5 hours at 25 C. A complete conversion was confirmed by gas chromatography. Then, dilute hydrochloric acid (7 N, 50 ml) was added, stirred for 5 minutes and extracted with ethyl acetate (3 50 ml). The combined organic fractions were dried over MgSO 4. After removal of the volatile components, purification by column chromatography was carried out. Alternatively, acetic acid anhydride can be used for derivatisation, but the use of propionic anhydride allows a more convenient isolation and matching micro analyses. Analytical data: Calculation of current efficiency (CE) Q [applied electric current]: in C [current time] Q [theoretically required electric current based on phenol]: in C [n(isolated phenol) 2 F] F: Faraday constant S6

7 2-Hydroxy-2,3,4,5 -tetramethoxy-5-methylbiphenyl (1ab): Purification: after removal of the solvents, recovering of starting materials by short-path-distillation was carried out. Column chromatography of the residue (cyclohexane/ethyl acetate = 4:1) yielded a slightly yellow solid. By washing with n-heptane (3 10 ml) on a glass frit and drying under reduced pressure an off-white powder was obtained. Mp: 171 C; R f (cyclohexane/ethyl acetate = 2:1): 0.33; 1 H NMR (300 MHz, CDCl 3 ) δ = 6.77 (s, 1H), 6.62 (s, 1H), 6.61 (d, J = 1.7 Hz, 1H), 6.57 (d, J = 1.7 Hz, 1H), 5.86 (s, 1H), 3.85 (s, 3H), 3.82 (s, 3H), 3.77 (s, 3H), 3.72 (s, 3H), 2.25 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , , , 98.47, 57.23, 56.43, 56.09, 55.94, 21.08; all analytic data are according to published results. 3 2-Acetoxy-2,3,4,5 -tetramethoxy-5-methylbiphenyl (1c): Purification: after completion of the derivatisation procedure using acetic acid anhydride, column chromatography was carried out (cyclohexane/ethyl acetate = 9:1 to 4:1). Removal of the solvent and drying under reduced pressure afforded a colorless solid. Mp: C; R f (cyclohexane/ethyl acetate = 4:1): 0.11; 1 H NMR (300 MHz, CDCl 3 ) δ = 6.77 (s, 1H), 6.76 (s, 1H), 6.61 (s, 1H), 6.59 (s, 1H), 3.93 (s, 3H), 3.84 (s, 3H), 3.80 (s, 3H), 3.72 (s, 3H), 2.37 (s, 3H), 2.07 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , , , , , 98.03, 56.80, 56.36, 56.04, 55.91, 21.48, 20.47; MS (EI, 70 ev): m/z(%): (38), (100), (25), (12), (14), (35), (9); (6); HRMS: m/z for C 19 H 22 O 6 calc: , found: ; micro analysis: calc (%): C 65.88, H 6.40, found (%): C 65.80, H Methyl-2-propionyloxy-2,3,4,5 -tetramethoxybiphenyl (1d): Purification: after completion of the derivatisation procedure using propionic anhydride column chromatography (cyclohexane/ethyl acetate = 9:1 to 4:1) was performed. Removal of the solvent and drying under reduced pressure afforded a colorless solid. Mp: C; R f (cyclohexane/ethyl acetate = 4:1): 0.18; 1 H NMR (400 MHz, CDCl 3 ) δ = 6.77 (s, 1H), 6.75 (s, 1H), 6.73 (s, 1H), 6.58 (s, 1H), 3.92 (s, 3H), 3.83 (s, 3H), 3.80 (s, 3H), 3.72 (s, 3H), 2.37 (s, 3H), 2.36 (q, J = 7.6 Hz, 2H), 1.06 (t, J = 7.6 Hz, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , , , , , , , , 98.00, 56.82, 56.33, 56.07, 55.95, 27.29, 21.50, 9.11; MS (EI, 70 ev): m/z(%): (21), (100), (17), (8); HRMS: m/z for C 20 H 24 O 6 calc: , found: ; micro analysis: calc (%): C 65.65, H 6.71, found (%): C 65.65, H S7

8 2-Hydroxy-3,4,5 -trimethoxy-2,5-dimethylbiphenyl (2ab): Purification: after removal of the solvents, recovering of starting materials by short-path-distillation was carried out. Column chromatography of the residue (cyclohexane/ethyl acetate = 4:1) yielded a slightly brown viscous mass. Storing at 5 C for 12 hours led to crystallization giving a yellow solid. After washing with n-heptane (3 10 ml) on a glass frit and drying under reduced pressure an off-white powder was obtained. Mp: C; R f (cyclohexane/ethyl acetate = 4:1): 0.18; 1 H NMR (300 MHz, CDCl 3 ) δ = 6.71 (s, 1H), (s, 1H), 6.62 (d, J = 1.7 Hz, 1H), 6.53 (d, J = 1.7 Hz, 1H), 5.37 (s, 1H), 3.84 (s, 3H), 3.83 (s, 3H), 3.77 (s, 3H), 2.25 (s, 3H), 2.08 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , , , , , 55.98, 55.94, 55.84, 21.08, 19.43; MS (EI, 70 ev): m/z(%): (100), (5), (9); HRMS: m/z for C 17 H 20 O 4 calc: , found: ; micro analysis: calc (%): C 70.81, H 6.99, found (%): C 70.39, H Hydroxy-2,3,4 -trimethoxy-5,6 -dime-thylbiphenyl (3ab) and 2-hydroxy-2,3,6 -trime-thoxy-4,5-dimethylbiphenyl (4ab): Purification: after removal of the solvents, recovering of starting materials by short-path-distillation was carried out. Column chromatography of the residue (cyclohexane/ethyl acetate = 9:1) led to a colorless powder which consists two regio isomers in the ratio of 4:1 for 3ab:4ab (GC). Several attempts of separation using various conditions failed. The solid was washed with n- heptane (3 10 ml) on a glass frit and dried in vacuo. Due to some overlap of several signals the major compound 3ab was only determined by NMR measurements. 1 H NMR (400 MHz, CDCl 3 ) δ = 6.59 (d, J = 1.5 Hz, 1H), 6.42 (d, J = 1.5 Hz, 1H), 6.37 (d, J = 2.2 Hz, 1H), 6.33 (d, J = 2.2 Hz, 1H), 5.22 (s, 1H), 3.81 (s, 3H), 3.74 (s, 3H), 3.62 (s, 3H), 2.33 (s, 3H), 1.99 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , , , , , , , 96.31, 55.85, 55.74, 55.18, 21.15, (2-Hydroxy-3-methoxy-5-methyl)-10-methylanthracene (5ab): Purification: after removal of the solvents, recovering of starting materials by short-pathdistillation was carried out. Column flash chromatography of the residue (cyclohexane/ethyl acetate = 9:1) yielded a bright yellow solid (0.428 g, 1.3 mmol, 26%). Mp: C; R f (cyclohexane/ethyl acetate=9:1): 0.43; 1 H NMR (300 MHz, CDCl 3 ) δ = 8.31 (d, J = 8.9 Hz, 2H), 8.15 (d, J = 8.6 Hz, 2H), (m, 2H), (m, 2H), 6.89 (d, J = 1.4 Hz), 6.34 (d, J = 8.2 Hz), 5.97 (d, J = 8.2 Hz), 4.11 (s, 3H), 3.10 (s, 3H), 2.26 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , 125.4, , , , , , , , 56.23, 21.02, 13.95; MS (EI, 70 ev): m/z(%): (20), S8

9 (28), (100), (20); HRMS: m/z for C 14 H Cl 2 O 4 calc: , found: ; micro analysis: calc (%): C 84.12, H 6.14, found (%): C 82.29, H (2-Hydroxy-3-methoxy-5-methylphenyl)-2-methoxynaphthalene (6ab): Purification: after removal of the solvents, recovering of starting materials by short-pathdistillation was carried out. Column chromatography of the residue (cyclohexane/ethyl acetate = 9:1 to 4:1) yielded a slightly yellow solid. After washing with n-heptane (3 10 ml) on a glass frit and drying under reduced pressure an off-white powder was obtained. Mp: 180 C; R f (cyclohexane/ethyl acetate = 4:1): 0.30; 1 H NMR (400 MHz, CDCl 3 ) δ = 7.80 (d, J = 9.0 Hz, 1H), (m, 1H), (m, 1H), 7.29 (d, J = 9.0 Hz, 1H), (m, 2H), 6.69 (d, J = 1.7 Hz, 1H), 6.56 (d, J = 1.9 Hz, 1H), 5.27 (s, 1H), 3.85 (s, 3H), 3.79 (s, 3H), 2.26 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , , , , , , , , 98.00, 56.82, 56.33, 56.07, 55.95, 27.29, 21.50, 9.11; all analytic data are according to published results. 3 1-(2-Hydroxy-3-methoxy-5-methylphenyl)-2,3-dimethoxynaphthalene (7ab): Purification: after removal of the solvents recovering of starting materials by short-pathdistillation was carried out. Column chromatography of the residue (cyclohexane/ethyl acetate = 9:1 to 4:1) yielded a slightly yellow solid. Recrystallizing in n-heptane/ethyl acetate = 9:1 (10 ml) and chilling to 4 C afforded a colorless solid which was filtered off by aid of a glass frit and dried under reduced pressure. Mp: 114 C; R f (cyclohexane/ethyl acetate = 4:1): 0.13; 1 H NMR (400 MHz, CDCl 3 ) δ = 7.65 (d, J = 8.1 Hz, 1H), (m, 2H), (m, 2H), 6.71 (d, J = 1.6 Hz, 1H), 6.57 (d, J = 1.6 Hz, 1H), 5.36 (s, 1H), 3.93 (s, 3H), 3.86 (s, 3H), 3.65 (s, 3H), 2.27 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , , , , , , , , , , , , 60.96, 55.91, 55.62, 21.18; MS (EI, 70 ev): m/z(%): (100), (24), (20), (7), (18), (10), (7); (10), (7); HRMS: m/z for C 20 H 20 O 4 calc: , found: ; micro analysis: calc (%): C 74.06, H 6.21, found (%): C 73.83, H Determination of the molecular structure of 7ab by X-ray analysis: Crystal structure determination of 7ab: C 20 H 20 O 4, M r = ; colourless block-like crystals (0.60 x 0.60 x 0.60 mm), obtained upon slow evaporation of the solvent from a CDCl 3 solution of 7ab at room temperature, T = 123(2) K, λ(mok α ) = Å, monoclinic, space group P2 1 /n (14), a= (7) Å, b=8.0411(5) Å, c= (8), β=104.24(0), a/b=1.5546, b/c=0.4741, c/a=1.3567, V = (127) Å 3, Z = 4, ρ calcd = g/cm 3, 2θ max = 56.0, μ = mm 1, F(000) = 688, reflections, 3914 unique reflections (R int = , completeness to θ = 97.9%), 226 parameters, GOF = 1.038, R 1 = [I > 2ς(I)], wr 2 = [all data], min./max. residual electron density 0.206/0.217 eå -3, CCDC In the solid state the biaryl is tilted by 78.28(3) forming one type of intramolecular hydrogen bonding (2.095(8) Å) between the hydroxyl and methoxy moieties (figure 4). π- stacking of the aromatic ring systems between different molecules of 7ab is the dominating S9

10 interactions for the dense packing containing no intermolecular hydrogen bondings. The mutual distance between the similarly arranged arene moieties is of about 3.4 Å (figure 4). Figure 3 Molecular structure of 7ab by X-ray analysis; left: top view, right: view along the biaryls axis Figure 4 Packing of 7ab in the solid state with hydrogen bonding highlighted in blue 4-(Dimethylamino)-1-(2-hydroxy-3-methoxy-5-methyl)-naphthalene (8ab): Purification: after removal of the solvents, recovering of starting materials by short-path- S10

11 distillation was carried out. Column flash chromatography of the residue (cyclohexane/ethyl acetate = 95:5) and drying in vacuo led to a brownish oil. R f (cyclohexane/ethyl acetate = 95:5): 0.10; 1 H NMR (300 MHz, CDCl 3 ) δ = (m, 2H), (m, 2H), 6.92 (d, J = 8.4 Hz, 1H), 6.83 (s, 1H), (m, 3H), 3.85 (s, 3H), 2.84 (s, 6H), 2.34 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , , , , , , , , , 55.93, 45.27, MS (EI, 70 ev): m/z(%): (100), (8), (28), (32); HRMS: m/z for C 20 H 21 NO 2 calc: , found: , micro analysis: calc (%): C 78.15, H 6.89, N 4.56, found (%): C 78.12, H 6.65, N Hydroxy-5-propyl-2,3,4,5 - tetramethoxybiphenyl (9ab) and 4-propyl-2,2,4,5 -tetramethoxybiphenylether (9ab ): Purification: after removal of the solvents, recovering of starting materials by short-pathdistillation was carried out. Column flash chromatography of the residue (cyclohexane/ethyl acetate = 4:1) and drying in vacuo led to yellow-brown oils. The two regio isomers were obtained in the ratio of 3:1 for 9ab:9ab ). 9ab R f (cyclohexane/ethyl acetate = 4:1): 0.13; 1 H NMR (400 MHz, CDCl 3 ) δ = 6.80 (d, J = 1.5 Hz, 1H), 6.66 (s, 1H), (m, 2H), 6.60 (d, J = 8.1 Hz, 1H), 3.92 (d, J = 4.6 Hz, 6H), 3.83 (s, 3H), 3.77 (s, 3H), 2.57 (t, 2H), 1.66 (sext, 2H), 0.97 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , , , , 98.54, 57.29, 56.48, 56.14, 56.00, 37.84, 24.75, 13.90; MS (EI, 70 ev): (100), (8), (16), (12), (6); HRMS: m/z for C 19 H 24 O 5 calc: , found: , micro analysis: calc (%): C 68.66, H 7.28, found (%): C 68.89, H ab R f (cyclohexane/ethyl acetate = 4:1): 0.31; 1 H NMR (400 MHz, CDCl 3 ) δ = 6.80 (d, J = 1.9 Hz, 1H), 6.66 (s, 1H), (m, 2H),6.60 (d, J = 8.4 Hz, 1H) 3.93 (s, 3H), 3.92 (s, 3H), 3.83 (s, 3H), 3.77 (s, 3H), 2.57 (m, 2H), 1.66 (dq, J = 7.3 Hz, 2H), 0.92 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , , , , , 57.38, 56.50, 56.48, 55.93, 37.73, 24.64, 13.81; MS (EI, 70 ev): (100), (24), (8), (10), (12); HRMS: m/z for C 19 H 24 O 5 calc: found: ; micro analysis: calc (%): C 68.66, H 7.28, found (%): C 68.74, H (1,1-Dimethylethyl)-2-hydroxy-2,3,4,5 -tetramethoxybiphenyl (10ab): Purification: after removal of the solvents, recovering of starting materials by short-pathdistillation was carried out. Column flash chromatography of the residue (cyclohexane/ethyl acetate = 3:1) and drying in vacuo led to a beige solid. R f (cyclohexane/ethyl acetate = 3:1): 0.05; 1 H NMR (300 MHz, CDCl 3 ) δ = (m, 2H), 6.64 (s, 1H), 5.96 (s, 1H), 3.92 (s, 6H), S11

12 3.84 (s, 3H), 3.79 (s, 3H), 1.32 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , , , , 98.51, 57.20, 56.55, 56.16, 56.07, 34.48, 31.59; MS (EI, 70 ev): m/z(%): (100), (76), (8), (8); HRMS: m/z for C 20 H 26 O 5 calc: , found: ; micro analysis: calc (%): C 69.34, H 7.56, found (%): C 69.07, H Hydroxy-2,3,4,5,5 -pentamethoxybiphenyl (11ab): Purification: after removal of the solvents, recovering of starting materials by short-path-distillation was carried out. Column chromatography of the residue (cyclohexane/ethyl acetate = 4:1) yielded a red viscous mass. Storing at 5 C for 12 hours led to crystallization providing a yellow solid. After washing with n-heptane (3 10 ml) on a glass frit and drying under reduced pressure a slightly yellow powder was obtained. Mp: 116 C; R f (cyclohexane/ethyl acetate = 4:1): 0.17; 1 H NMR (400 MHz, CDCl 3 ) δ = 6.80 (s, 1H), (s, 1H), 6.45 (d, J = 2.8 Hz, 1H), 6.34 (d, J = 2.8 Hz, 1H), 5.72 (s, 1H), 3.86 (s, 3H), 3.83 (s, 3H), 3.78 (s, 3H), 3.74 (s, 3H), 3.72 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , , , , , , 98.87, 98.55, 57.32, 56.49, 56.13, 56.03, 55.72; MS (EI, 70 ev): m/z(%): (100), (6), (10), (13), (10), (5); HRMS: m/z for C 17 H 20 O 6 calc: , found: ; micro analysis: calc (%): C 63.74, H 6.29, found (%): C 63.41, H Hydroxy-2,3,4,5,5 -pentamethoxybiphenyl (12ab): Purification: after removal of the solvents recovering of starting materials by short-path-distillation was carried out. By column chromatography of the residue (cyclohexane/ethyl acetate = 2:1) a slightly yellow viscous mass was obtained. Recrystallization from boiling n-heptane (30 ml) and storing at 5 C for 12 hours led to crystallization of an off-white solid. After washing with n- heptane (3 10 ml) on a glass frit and drying in vacuo a colorless solid was received. Mp: 123 C; R f (cyclohexane/ethyl acetate = 2:1): 0.14; 1 H NMR (400 MHz, CDCl 3 ) δ = 6.79 (s, 1H), (s, 2H), 6.55 (s, 1H), 5.46 (s, 1H), 3.86 (s, 3H), 3.84 (s, 6H), 3.80 (s, 3H), 3.69 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , , , , , 98.69, 56.84, 56.73, 56.34, 56.20; MS (EI, 70 ev): m/z(%): (100), (6), (5); HRMS: m/z for C 17 H 20 O 6 calc: , found: ; micro analysis: calc (%): C 63.74, H 6.29, found (%): C 63.50, H ,5-Dimethyl-2-hydroxy-2,4,5 -trimethoxybiphenyl (13ab): Purification: after removal of the solvents, recovering of starting materials by short-path-distillation was carried out. Column chromatography of the residue (cyclohexane/ethyl acetate = 9:1 to 3:1) yielded a slightly yellow solid. Washing with n-heptane (2 10 ml) on a glass frit and drying in vacuo revealed a colorless solid. Mp: 98 C; R f (cyclohexane/ethyl acetate = 4:1): 0.29; 1 H NMR (400 MHz, CDCl 3 ) δ = 6.90 (d, J = 1.6 Hz, 1H), 6.81 (s, J = 1.6 Hz, 1H), 6.76 (s, 1H), 6.58 (s, S12

13 1H), 6.33 (s, 1H), 3.87 (s, 3H), 3.79 (s, 3H), 3.76 (s, 3H), 2.72 (s, 6H); 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , , , , , , , 98.37, 57.45, 56.48, 56.20, 20.52, 16.44; All analytic data are according to published results. 3 3-Chloro-2-hydroxy-5-methyl-2',4',5'-trimethoxybiphenyl (14ab): Purification: after removal of the solvents, recovering of starting materials by short-pathdistillation was carried out. Column chromatography of the residue (cyclohexane/ethyl acetate = 3:1) yielded a colourless solid. Mp: C; R f (cyclohexane/ethyl acetate = 3:1): 0.22; 1 H NMR (300 MHz, CDCl 3 ) δ = 7.18 (d, J = 2.1 Hz, 1H), 6.96 (d, J = 2.1 Hz, 1H), 6.81 (s, 1H), 6.65 (s, 1H), 6.42 (s, 1H), 3.95 (s, 1H), 3.87 (s, 1H), 3.84 (s, 1H), 2.30 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , , , 98.29, 57.45, 56.54, 56.19, MS (EI, 70 ev): m/z(%): (100), (36), (16), (20); HRMS: m/z for C 16 H ClO 4 calc: , found: ; micro analysis: calc (%): C 62.24, H 5.55, found (%): C 62.18, H Determination of the molecular structure of 14ab by X-ray analysis: Crystal structure determination of 14ab: C 16 H 17 ClO 4, M r = ; colourless block-like crystals (0.32 x 0.26 x 0.12 mm), obtained upon slow evaporation of the solvent from a CDCl 3 solution of 14ab at room temperature, T = 100(2) K, λ(mok α ) = Å, monoclinic, space group C2/c, a= (10) Å, b= (6) Å, c= (12) Å, α=90, β= (10), γ=90, a/b=1.7253, b/c=0,7787, c/a=0.7443, V = (3) Å 3, Z = 8, ρ calcd = g/cm 3, 2θ max = 56.0, μ = mm 1, F(000) = 1296, reflections, 2822 unique reflections (R int = , completeness to θ = 97.5%), 195 parameters, GOF = 1.033, R 1 = [I > 2ς(I)], wr 2 = [all data], min./max. residual electron density 0.199/0.264 eå -3, CCDC In the solid state the biaryl is tilted by (5) (figure 5). A hydrogen bonding network between different molecules of 14ab is the dominating interactions for the dense packing containing two equivalent hydrogen bondings of parallel directions and distances (2.1155(1) Å). The mutual distance between the similarly arranged arene moieties is of about 3.5 Å (figure 6). Figure 5 Molecular structure of 14ab by X-ray analysis; left: top view, right: view along the biaryls axis S13

14 Figure 6 Packing of 14ab in the solid state with hydrogen bonding highlighted in blue 3-Bromo-2-hydroxy-5-methyl-2,4,5 -trimethoxybiphenyl (15ab): Purification: after removal of the solvents, recovering of starting materials by short-pathdistillation was carried out. Column chromatography of the residue (cyclohexane/ethyl acetate = 9:1) revealed an off-white solid. Washing with n-heptane (2 10 ml) on a glass frit and drying in vacuo yielded a colorless solid. Mp: C; R f (cyclohexane/ethyl acetate = 4:1): 0.23; 1 H NMR (400 MHz, CDCl 3 ) δ = 7.26 (d, J = 1.6 Hz, 1H), 6.92 (d, J = 1.6 Hz, 2H), 6.72 (s, 1H), 6.57 (s, 1H), 6.39 (s, 1H), 3.87 (s, 3H), 3.79 (s, 3H), 3.76 (s, 3H), 2.23 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ = , , , , , , , , , , , 98.27, 57.41, 56.53, 56.17, 20.26; MS (EI, 70 ev): m/z(%): 354.1, (97, 100), 339.0, (32, 32), 309.0, (13, 13), 307.0, (8, 8), (18), (30), (11); (15), (15), (5), (7), 69.1 (5); HRMS: m/z for C 20 H BrO 4 calc: , found: ; micro analysis: calc (%): C 54.41, H 4.85, found (%): C 54.37, H Determination of the molecular structure of 15ab by X-ray analysis: Crystal structure determination of 15ab: C 20 H 20 BrO 4, M r = ; colourless block-like crystals (0.60 x 0.48 x 0.40 mm), obtained upon slow evaporation of the solvent from a CDCl 3 solution of 15ab at room temperature, T = 123(2) K, λ(mok α ) = Å, monoclinic, space group C2/c (15), a= (5) Å, b= (3) Å, c= (4) Å, β=131.51(0), a/b=1.7029, b/c=0.7852, c/a=0.7478, V = (529) Å 3, Z = 8, ρ calcd = g/cm 3, 2θ max = 56.0, μ = mm 1, F(000) = 1440, reflections, 3604 unique reflections (R int = , completeness to θ = 99.7%), 196 parameters, GOF = 1.057, R 1 = [I > 2ς(I)], wr 2 = [all data], min./max. residual electron density /0.417 eå -3, CCDC In the solid state the biaryl is tilted by 71.89(7) forming no intramolecular hydrogen bondings (figure 7). A hydrogen bonding network between different molecules of 15ab is the dominating interactions for the dense packing containing two types of hydrogen bondings of different S14

15 directions and distances (2.106(7) Å, 2.519(5) Å). The mutual distance between the similarly arranged arene moieties is of about 3.9 Å (figure 8). Figure 7 Molecular structure of 15ab by X-ray analysis; left: top view, right: view along the biaryls axis Figure 8 Packing of 15ab in the solid state with hydrogen bonding highlighted in blue 3-Methoxy-2-propionyloxy-1-(2,4,5-trimethoxyphenyl)naphthalene (16d): Purification: after removal of the solvents, recovering of starting materials by short-pathdistillation was carried out. Column chromatography of the derivatized residue (cyclohexane/ethyl acetate = 3:1) yielded a slightly yellow solid. Mp: C; S15

16 R f (cyclohexane/ethyl acetate = 3:1): 0.19; 1 H NMR (300 MHz, CDCl 3 ) δ = (m, 1H, H-5), (m, 2H), (m, 2H), 6.71 (s, 1H), 6.61 (s, 1H), 3.96 (s, 3H), 3.93 (s, 3H), 3.76 (s, 3H), 3.62 (s, 3H), (m, 2H), 1.03 (t, J = 7.5 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , , , , , , , , , 98.25, 57.06, 56.47, 56.21, 55.99, 27.41, 9.29; MS (EI, 70 ev): m/z(%): (24), (100), (16), (12); HRMS: m/z for C 23 H 25 O 6 calc: , found: ; micro analysis: calc (%): C 69.68, H 6.10, found (%): C 69.32, H Determination of the molecular structure of 16d by X-ray analysis: Crystal structure determination of 16d: C 23 H 24 O 6, M r = ; colorless block-like crystals (0.60 x 0.40 x 0.30 mm), obtained upon slow evaporation of the solvent from a CDCl 3 solution of 16d at room temperature, T = 123(2) K, λ(mok α ) = Å, monoclinic, space group P2 1 /c, a= (11) Å, b= (5) Å, c= (13) Å, β= (4), a/b=2.5148, b/c=0.4340, c/a=0.9163, V = (2) Å 3, Z = 4, ρ calcd = g/cm 3, 2θ max = 56.0, μ = mm 1, F(000) = 840, reflections, 4681 unique reflections (R int = , completeness to θ = 99.3%), 267 parameters, GOF = 0.879, R 1 = [I > 2ς(I)], wr 2 = [all data], min./max. residual electron density /0.218 eå -3, CCDC In the solid state the biaryl is twisted by 68.64(6) forming no intramolecular hydrogen bondings (figure 9). π- stacking of the aromatic ring systems between different molecules of 16d is the dominating interactions for the dense packing containing no intermolecular hydrogen bondings. The mutual distance between the similarly arranged arene moieties is of about 3.7 Å (figure 10). Figure 9 Molecular structure of 16d by X-ray analysis; left: top view, right: view along the biaryls axis S16

17 Figure 10 Packing of 16d in the solid state 3-Bromo-2',4',5'-trimethoxy-1,2,5-trimethyl-1,1'- biphenyl-4(1h)-one (17ab) and 3-bromo-2',4',5'-trimethoxy-1,4,5-trimethyl-1,1'-biphenyl- 2(1H)-one (18ab): Purification: after removal of the solvents, recovering of starting materials by short-path-distillation was carried out. Column flash chromatography of the residue (cyclohexane/ethyl acetate = 4:1) and drying in vacuo led to a bright yellow (17ab) solid and a slightly yellow (18ab) solid. 17ab Mp: C; R f (cyclohexane/ethyl acetate = 4:1): 0.14; 1 H NMR (400 MHz, CDCl 3 ) δ = 6.91 (s, 1H), 6.47 (s, 1H), 5.80 (d, J = 1.2 Hz, 1H), 3.89 (s, 3H), 3.84 (s, 3H), 3.54 (s, 3H), 2.37 (s, 3H), 2.00 (d, J = 1.2 Hz, 3H), 1.48 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , , , 98.99, 56.86, 56.72, 56.12, 51.91, 23.12, 22.27, 20.61;MS (EI, 70 ev): m/z(%): (98), (100), (12), (12), 351 (98), 349 (100), (44), (84); HRMS: m/z for C 18 H 22 O 7 calc: , found: ; micro analysis: calc (%): C 56.70, H 5.55, found (%): C 56.86, H ab Mp: C; R f (cyclohexane/ethyl acetate = 4:1): 0.12; 1 H NMR (400 MHz, CDCl 3 ) δ = 6.89 (s, 1H), 6.49 (d, J= 1.3 Hz, 1H), 6.45 (s, 1H), 3.89 (s, 3H), 3.88 (s, 3H), 3.56 (s, 3H), 1.94 (d, J = 1.3 Hz, 3H), 1.87 (s, 1H), 1.59 (s, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ = , , , , , , , , , 98.44, 57.14, 56.45, 56.03, 48.49, 24.67, 21.84, 16.37; MS (EI, 70 ev): m/z(%): (98), (100), (20), (20), 351 (60), 349 (60), (22), (40); HRMS: m/z for C 18 H 22 O 7 calc: , found: ; micro analysis: calc (%): C 56.70, H 5.55, found (%): C 56.90, H Determination S17

18 of the molecular structure of 18ab by X-ray analysis: Crystal structure determination of 18ab: the crystals turned out to be systematically non-merohedrally twinned. The diffraction pattern could be indexed as a 2-component twin using the least-squares procedure. 9 Subsequent multi-domain integration of the data set led to a refined twin law of ( ). The data reduction and empirical absorption correction with TWINABS 10 gave a HKLF 5 file suitable for the twin refinement in SHELX, C 18 H 21 BrO 4, M r = ; slightly yellow platelets (0.42 x 0.40 x 0.08 mm), obtained upon slow evaporation of the solvent from a CDCl 3 solution of 18ab at room temperature, T = 123(2) K, λ(mok α ) = Å, monoclinic, space group P21/c, a=11.075(2) Å, b=12.387(3) Å, c=12.712(3) Å, β= (5), a/b=0.8941, b/c=0.9744, c/a=1.1478, V = (6) Å 3, Z = 4, ρ calcd = g/cm 3, 2θ max = 54.0, μ = mm 1, F(000) = 784, reflections, 3694 unique reflections (R int = , completeness to θ = 99.8%), 214 parameters, GOF = 1.067, R 1 = [I > 2ς(I)], wr 2 = [all data], refined twin BASF = , min./max. residual electron density /0.815 eå -3, CCDC In the solid state the biaryl is tilted by (5) and twisted by (13) forming no intramolecular hydrogen bondings (figure 11). The mutual distance between the similarly arranged arene moieties is of about 4.4 Å (figure 12). Figure 11 Molecular structure of 18ab by X-ray analysis; left: top view, right: view along the aryl-cyclohexadienyl axis S18

19 Figure 12 Packing of 18ab in the solid state 3,4,5-Trimethoxy-4-(2,4,5-trimethoxyphenyl)-cyclohexa-2,5-dienone (19ab): Purification: recovering of starting material by short-path-distillation was carried out. Column chromatography of the residue (cyclohexane/ethyl acetate = 1:5) and drying in vacuo yielded a slightly yellow solid (0.505 g, 1.4 mmol, 29%). Mp: C; R f (cyclohexane/ethyl acetate = 1:5): 0.21; 1 H NMR (300 MHz, CDCl 3 ) δ = 7.40 (s, 1H), 6.41 (s, 1H), 5.66 (s, 2H), 3.89 (s, 3H), 3.84 (s, 3H), 3.62 (s, 6H), 3.57 (s, 3H), 3.24 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , 97.74, 88.00, 76.29, 56.41, 56.39, 56.21, 55.90, 51.12; MS (EI, 70 ev): m/z(%): (100), (12), (12, (16), (16), (12); HRMS: m/z for C 18 H 22 O 7 calc: , found: ; Micro analysis: calc (%): C 61.71, H 6.33, found (%): C 61.44, H Determination of the molecular structure of 19ab by X-ray analysis: crystal structure determination of 19ab: C 18 H 22 O 7, M r = ; colourless needle-like crystals (0.32 x 0.24 x 0.02 mm), obtained upon slow evaporation of the solvent from a CDCl 3 solution of 19ab at room temperature, T = 123(2) K, λ(mok α ) = Å, orthorhombic, space group Pbca, a= (4) Å, b=7.3238(2) Å, c= (8) Å, α=β=γ=90, a/b = , b/c = , c/a = , V = (15) Å 3, Z = 8, ρ calcd = g/cm 3, 2θ max = 56.0, μ = mm 1, F(000) = 1488, reflections, 4011 unique reflections (R int = , completeness to θ = 99.8%), 233 parameters, GOF = 0.899, R 1 = [I > 2ς(I)], wr 2 = [all data], min./max. residual electron density 0.256/0.239 eå -3, CCDC In the solid state the biaryl is tilted by (17) and twisted by (4) (figure 13). The minimization of polarity between different molecules of 19ab is the dominating interactions for the dense packing (figure 14). S19

20 Figure 13 Molecular structure of 19ab by X-ray analysis; left: top view, right: view along the aryl axis Figure 14 Packing of 19ab in the solid state 2',4',5'-Trimethoxy-1,3-dimethyl-1,1'-biphenyl-2(1H)-one (20ab): Purification: after removal of the solvents recovering of starting materials by short-pathdistillation was carried out. Column flash chromatography of the residue (cyclohexane/ethyl acetate = 4:1) and drying in vacuo led to a dark orange solid. Mp: 94 C; R f (cyclohexane/ethyl acetate = 4:1): 0.12; 1 H NMR (400 MHz, CDCl 3 ) δ = 6.92 (s, 1H), (m, 1H), 6.45 (s, S20

21 1H), 6.09 (dd, J = 9.3 Hz, 6.0 Hz, 1H), 5.97 (dd, J = 9.3Hz, 0.8 Hz, 1H), 3.87 (s, 3H), 3.82 (s, 3H), 3.52 (s, 3H), 1.94 (s, 3H), 1.43 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ = , , , , , , , , , , 98.90, 56.85, 56.41, 56.13, 51.50, 22.70, 15.81; MS (EI, 70 ev): (100), (20), 260 (22), (88), (20); HRMS: m/z for C 19 H 24 O 5 calc: , found: ; micro analysis: calc (%): C 70.81, H 6.99, found (%): C 70.83, H NMR Spectra: Starting materials: S21

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45 References: 1. Blessing, R. H. Acta Cryst. A, 1995, 51, Sheldrick, G.M. SHELXS97 and SHELXL97: Programm for the Refinement of Crystal Structures; Dept. of Structural Chemistry, University of Göttingen: Germany, Kirste, A.;Schnakenburg, G.;Stecker, F; Fischer, A; Waldvogel, S. R. Angew. Chem. Int. Ed. 2010, 49, Michel, F.; Thomas, F; Hamman, S; Saint-Aman, E.; Bucher, C. P. J. J. Chem.-Eur. J. 2004, 10, Bolchi, C.; Catalano, P.; Fumagalli, L.; Gobbi, M.; Pallavicini, M.; Pedretti, A.; Villa, L.; Vistoli, G.; Valoti, E. Bioorg. Med. Chem. 2004, 12, Tietze, L. F.; Spiegl, D. A.; Stecker, F.; Major, J.; Raith, C.; Große, C. Chem.-Eur. J. 2008, 14, Goksu, S. Kazaz, C. Sutbeyaz, Y., Secen, H. Helv. Chim. Act. 2003, 86, Malkowsky, I. M.; Griesbach, U.; Pütter, H.; Waldvogel, S. R. Eur. J. Org. Chem. 2006, Sheldrick, G.M. CELL_NOW, 2009/2, Bruker AXS, Madison: Wisconsin, WI, Sheldrick, G.M. TWINABS, 2009/2, Bruker AXS, Madison: Wisconsin, WI, S45