4- Cyano-benzene-boronic acid

Scheme 2 Synthesis of 4-cyano-benzene-boronic acid...

Experimental conditions 5-bromoindole 3(1 mmol), 4-cyano-benzene-boronic acid 4 (1.5 mmol), sodium carbonate (2 mmol) and the catalyst were heated in a 50 ml Schlenk-tube to 80 °C in toluene (6 ml), ethanol (1 ml) and water (1 ml) for the indicated time. The conversion was determined by GLC... 

Synthesis of 4-cyano-benzene-boronic acid 4. A vacuum isolated triple jacket reactor was charged with THF (76.5 g), triisopropylborate (49.8 g, 265 mmol), and toluene (88 g), and the mixture was cooled to —70°C. A solution of 4-bromo-benzonitrile 2 (40 g, 220 mmol) in toluene (210 g) was added within 20 min and a fine suspension is formed. BuLi (15% in hexane, 131 g, 308 mmol) was added dropwise within 4 h keeping the reaction temperature below —70°C. Hydrochloric... 

Synthesis of 5-(4-cyano-phenyl)-indole 1. A double jacket reactor was charged with 5-bromo-indole 3 (50 g, 250 mmol), 4-cyano-benzene-boronic acid 4 (38.7 g, 263 mmol), and isopropanol (393 g). The reactor was purged with nitrogen. Pd(PTol3)2Cl2 (0.2 g, 0.25 mmol) was added, and the reaction mixture was heated to reflux. Sodium carbonate solutimi (2 M, 250 ml, 500 mmol) was dosed within 2 h. The reaction was stirred for additional 90 min at reflux. The isopropanol was distilled off until the temperature of the distillation residue reached lOO C. The reaction mixture was cooled to room temperature and was extracted with dichloromethane (1,000 ml). The organic phase was extracted with water (250 ml) and was filtered slowly through a bed of silica (40 g) and charcoal (4 g). The filter bed was washed with dichloromethane (100 ml). To the combined dichloromethane phases, toluene (500 ml) was added and dichloromethane was distilled of until the distillation residue reached a temperature of 110°C. The product solution was cooled to 95°C and was seeded. The suspension was cooled slowly (l°C/min) to room temperature. The product is filtered, washed with toluene (50 ml), and dried at 60°C. 5-(4-cyano-phenyl)-indole 1 was obtained as colorless crystals (42.6 g, 188 mmol, 75%). 

To introduce the cyano group at C-1, diethylaluminum cyanide can be used in benzene solution without a catalyst and gives anomeric mixtures of the a,/ ano-mers, the ratios of which depend on the temperature used [42] (Sect. 3). Otherwise trimethylsilyl cyanide together with boron trifluoride etherate can be employed to introduce the cyano group [40,41]. Organozinc derivatives of the Reformatski type, e. g. (cyanoethyl)zinc iodide, can be used with Lewis acid catalysis [64] exceptionally, however, zinc/copper analogues favour the formation of C-3-substituted glycals [65]. 

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