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All reactions were carried out with magnetic stirring and, if air or moisture sensitive, in flame- dried glassware under argon. Syringes were used to transfer reagents, and solvents were purged with argon prior to use.

Solvents

Solvents were dried according to standard methods by distillation from drying agents as stated below and were stored under argon.

CH2Cl2 and toluene were predried over CaCl2(s) and distilled from CaH2(s).

Diethyl ether and THF were continueously refluxed and freshly distilled from sodium benzophenone ketyl under nitrogen.

1,2-dimethoxyethane (DME) was predried over CaCl2(s) and freshly distilled from sodium benzophenone ketyl under nitrogen.

Dimethylformamide (DMF) was heated to reflux for 14 h over CaH2(s) and distilled from CaH2(s).

Ethanol was treated with Phthalic anhydride (25g/L) and sodium, heated to reflux for 6 h and distilled.

Methanol was treated with magnesium turnings (20g/L) and sodium, heated to reflux for 6 h and distilled.

Pyridine and triethylamine were dried over KOH(s) and distilled from KOH(s).

Reagents

Reagents of >98% purity were used as obtained.

n-Butyllithium was used as a 1.5 M solution in hexane purchased by Chemetall.

CuCN·2LiCl solution (1.0 M/THF) was prepared by drying CuCN (869 mg, 10 mmol) and LiCl (848 mg, 20 mmol) in a Schlenk flask under vacuum for 5 h at 140 °C. After cooling to room temperature, dry THF (10 mL) was added and stirred continuously until the salts were dissolved.

Phenylmagnesium chloride was used as a 2.0 M solution in THF purchased by Chemetall. i-PrMgCl: A dry three-necked flask equipped with an argon inlet, a dropping funnel and a

thermometer was charged with magnesium turnings (110 mmol). A small amount of THF was added to cover the magnesium, and a solution of isopropyl chloride (100 mmol) in THF (50 mL) was added dropwise, keeping the temperature of the mixture below 30 °C (water bath). After the addition was complete, the reaction mixture was stirred for 12 h at room temperature. The grey solution of i-PrMgCl was cannulated to another flask under argon and removed in this way from excess of magnesium. A yield of ca. 95-98 % of i-PrMgCl was

Experimental Part 92 obtained and the i-PrMgCl-solution was titrated prior to use according to reported literature.105

i-PrMgCl·LiCl: A dry three-necked flask equipped with an argon inlet, a dropping funnel and

a thermometer was charged with magnesium turnings (110 mmol) and anhydrous LiCl (100 mmol). A small amount of THF was added to cover the magnesium, and a solution of isopropyl chloride (100 mmol) in THF (50 mL) was added dropwise, keeping the temperature of the mixture below 30 °C (water bath). After the addition was complete, the reaction mixture was stirred for 12 h at room temperature. The grey solution of i-PrMgCl·LiCl was cannulated to another flask under argon and removed in this way from excess of magnesium. A yield of ca. 95-98 % of i-PrMgCl·LiCl was obtained and the i-PrMgCl·LiCl-solution was titrated prior to use according to reported literature.105

TMPMgCl·LiCl: A dry and nitrogen-flushed 250 mL Schlenk flask, equipped with a magnetic stirrer and a septum, was charged with freshly titrated i-PrMgCl·LiCl(100 mL, 1.2 M in THF, 120 mmol). 2,2,6,6-Tetramethylpiperidine (TMPH) (19.8 g, 126 mmol, 1.05 equiv.) was added dropwise at room temperature. The reaction mixture was stirred at room temperature until gas evolution was completed (ca. 24 h).20 The concentration of the solution of TMPMgCl·LiCl was titrated by using benzoic acid in dry THF and 4- (phenylazo)diphenylamine as an indicator.

ZnBr2 solution (1.0 M/THF) was prepared by drying ZnBr2 (33.78 g, 150 mmol) under

vacuum for 5 h at 150 °C. After cooling to room temperature, dry THF (150 mmol) was added and stirred continuously until the salts were dissolved.

ZnCl2 solution (1.0 M/THF) was prepared by drying ZnCl2 (20.45 g, 150 mmol) under

vacuum for 5 h at 150 °C. After cooling to room temperature, dry THF (150 mmol) was added and stirred continuously until the salts were dissolved.

The following reagents were prepared according to literature procedures:

2,6-diiodophenol,106 tert-butyl-(1-ethoxy-vinyloxy)-dimethyl-silane, 107 2-iodo-benzene-1,3- diol (28),75c 3-hydroxy-4-iodopyridine,84 2-Methoxy-pyridin-3-ol,86 4-{[(4-chlorophenyl) sulfonyl]oxy}-3-iodobenzonitrile (27q),79 allyl-phenyl-amine, 108 4-(allylamino) benzonitrile,108 _{palladium(II)bis(dibenzylidenacetone),}109 _{tri-(2-furyl)phosphine.}110

Chromatography

Thin layer chromatography (TLC) was performed using aluminium plates coated with SiO2 (Merck 60, F-254). The spots were visualized by UV light and/or by staining of the TLC plate with the solution bellow followed by heating with a heat gun:

• KMnO4 (0.3 g), K2CO3 (20 g), KOH (0.3 g) in water (300 mL)

105 _{(a) H. S. Lin, L. Paquette, Synth. Commun.}

1994, 24, 2503; (b) A. Krasovskiy, P. Knochel, Synthesis 2006, 5, 890.

106 _{S. Adimurthy, G. Ramachandraiah, Tetrahedron Lett.}

2004, 45, 5251. 107 _{J. S. Nowick, R. L. Danheiser, Tetrahedron}

1988, 44, 4113. 108 _{S.-C. Yang, C.-W. Hung, Synthesis}

1999, 1747. 109 _{Y. Takahashi, T. Ito, S. Sakai, Chem. Comm.}

1970, 1065.

110 _{D. W. Allen, B. G. Hutley, M. T. J. Mellor, J. Chem. Soc. Perkin Trans. II}

Experimental Part 93 Flash column chromatography was performed using SiO2 60 (0.04-0.063 mm, 230-400 mesh ASTM) from Merck. The diameters of the columns and the amount of silicagel were calculated according to the recommendation of W. C. Still.111

Analysis

Analytical data collection was done as follows:

• Melting points were uncorrected and measured on a Büchi B-540 apparatus. • NMR spectra were recorded on a Bruker ARX 200, AC 300, WH 400, or AMX

600 instruments. Chemical shifts were given relative to CDCl3 (7.26 ppm for 1H NMR, 77.0 ppm for 13C NMR), DMSO-d6 (2.50 ppm for 1H NMR, 39.4 ppm for 13_{C NMR), acetone-d6 (2.04 ppm for} 1_{H NMR, 29.3 ppm for} 13_{C NMR). For the} characterization of the observed signal multiplicities the following abbreviations were applied: s (single), d (doublet), dd (double doublet), dt (double triplet), t (triplet), td (triple doublet), q (quartet), quint (quintet), m (multiplet), as well as br (broad).

• IR spectra were recorded from 4000-400 cm-1 on a Nicolet 510 FT-IR, a Perkin- Elmer 281 IR spectrometer, or a Perkin Elmer Spectrometer BX FT-IR-System with a Smith Dura sampl IR II ATR-unit. Samples were measured either as neat materials (neat) or as a film between potassium bromide plates (film) or as potassium bromide tablets (KBr). The absorption bands are reported in wave numbers (cm-1). For the band characterization the following abbreviations were applied: br (broad), s (strong), m (medium), vs (very strong), w (weak).

• Gas chromatography (GC) was perfomed using a Hewlett-Packard 5890 Series II (Column A: 2.5 % phenylmethylpolysiloxane (HP Ultra 2) 12 m × 0.2 mm × 0.33

μm). The compounds were detected with a flame ionization detector.

• Mass spectroscopy: Mass spectra were recorded on a Varian MAT CH 7A for electron impact ionization (EI) and high resolution mass spectra (HRMS) on a Varian MAT 711 spectrometers. Fast atom bombardment (FAB) samples were recorded in either a 2-nitrobenzyl alcohol- or glycerine-matrix. Additionally, for the combination of gas chromatography with mass spectroscopic detection, a GC/MS from Hewlett-Packard HP 6890/MSD 5973 was used (Column B: 5 % phenylmethylpolysiloxane (HP 5) 30 m × 0.25 mm × 0.25 μm; Column C: 5 % phenylmethylpolysiloxane (HP 5) 15 m × 0.25 mm × 0.25 μm).

• Elemental analysis was carried out on a Heraeus CHN-Rapid-Elementanalyzer in the microanalytical laboratories of the Department Chemie und Biochemie, Ludwig-Maximilians Universität, Munich.

111 _{W. C. Still, M. Khan, A. Mitra, J. Org. Chem.}

Experimental Part 94