A dramatic enhancing effect of InBr₃ towards the oxidative Sonogashira cross-coupling reaction of 2-ethynylanilines

Abstract

The addition of InBr3 to the oxidative Sonogashira cross-coupling reaction of 2-ethynylaniline with (E)-trimethyl(3,3,3-trifluoroprop-1-enyl)silane led to a dramatic increase in the reactivity to afford the corresponding 1,3-enynes bearing a trifluoromethyl group on their terminal sp(2) carbon. The subsequent cyclization of these 1,3-enynes under palladium catalysis provides access to the corresponding indoles bearing a 3,3,3-trifluoroprop-1-enyl group at their 2-position.

NCBSI/KI: A Reagent System for Iodination of Aromatics through In Situ Generation of I-Cl

“…The crude product was recrystallized in 1:1 ethanol−water and dried under vacuum to obtain 2-iodo-4-nitroaniline, 2a,1.84 g (96% yield, 98.9% purity) as yellow crystalline solid: mp 105−107 °C (lit. 34 General Procedure for the Di-iodination Reaction. To a solution of KI (2.4 g, 14.48 mmol) in anhydrous DMF (8.0 mL), cooled to 15−20 °C, was added NCBSI (4.8 g, 14.48 mmol) in portions while the temperature was maintained at 15−20 °C.…”

“…The experimental procedure followed for the synthesis of 2a using 2-nitroaniline (1.0 g, 7.24 mmol) substrate produced 1.85 g (97% yield, 98.8% purity) as a yellow crystalline solid: mp 121−123 °C (lit. 34 mp 124−125 °C); 1 H NMR (400 MHz, CDCl 3 ) δ 8.41 (d, J = 1.9 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 6.59 (d, J = 8.8 Hz, 1H), 6.08 (s, 2H).…”

“…The filtrate was quenched and stirred with a 25 mL mixture of 1% sodium thiosulfate and 5% sodium bicarbonate solution (1:1) for 15 min, and the product precipitated was filtered. The crude product was recrystallized in 1:1 ethanol–water and dried under vacuum to obtain 2-iodo-4-nitroaniline, 2a ,1.84 g (96% yield, 98.9% purity) as yellow crystalline solid: mp 105–107 °C (lit . mp 106–107 °C); 1 H NMR (400 MHz, CDCl 3 ) 8.56 (d, J = 2.4 Hz, 1H), 8.06 (dd, J = 8.9, 2.5 Hz, 1H), 6.70 (d, J = 8.9 Hz, 1H), 4.85 (s, 2H).…”

Synthesis of Asthma Drug Zafirlukast (Accolate) Using Intramolecular Oxidative Coupling via sp3 C–H Bond Activation

“…To add value to this reaction, appropriately substituted alkynyl aniline derivative 5f was prepared in a one-pot threestep process. 2-bromoaniline 7 was subjected to Sonogashira coupling with trimethylsilyl-acetylene using palladium catalyst, followed by desilylation with the addition of K 2 CO 3 40 and subsequent Sonogashira coupling in the same flask with methyl 4-iodo-3-methoxybenzoate 10 furnished 5f in 58% overall yield over three steps (Scheme 3). To our satisfaction, sodium persulfate in hot dimethyl sulfoxide (DMSO), in absence of any external catalyst, facilitated the entire sequence of sp 3 The task of converting 6f to zafirlukast was accomplished following four easy synthetic transformations (Scheme 3).…”

Synthesis of Small Fluorescent Molecules and Evaluation of Photophysical Properties

“…For this purpose, two compounds with the simplest substitution pattern, 2-TFPE-aniline ( 3a ) and 4-TFPE-aniline ( 3b ), were prepared to determine their fluorescent responses. For the synthesis, they were obtained in moderate yields based on our previous report using the Hiyama cross-coupling reaction of corresponding aryl iodide with ( E )-3,3,3-trimethyl­(3,3,3-trifluoro-1-propenyl)­silane ( 2 ) . Their photophysical properties, fluorescence emissions, molar absorption coefficients (ε), and quantum yields (Φ f ), were measured as shown in Table .…”