1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane Bis(tetrafluoroborate) as Novel and Versatile Reagent for the Rapid Thiocyanation of Indoles, Azaindole, and Carbazole J. S. Yadav,  B. V. Subba Reddy, and Y. Jayasudhan Reddy Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India (Received January 30, 2008; CL-080107; E-mail: yadavpub@iict.res.in) SelectfluorÔ is found to catalyze efficiently the electrophilic thiocyanation of indoles and pyrrole with ammonium thiocya- nate under mild and neutral conditions to produce the corre- sponding 3-indolyl and 2-pyrrolyl thiocyanates, respectively, in excellent yields with high selectivity. This method is effective even with azaindole and carbazole while many of reported procedures failed to produce thiocyanates from azaindole. The electrophilic thiocyanation of aromatics and heteroaro- matics is one of the most important carbon–heteroatom bond- forming reactions in organic synthesis. 1 Aryl and heteroaryl thiocyanates are useful intermediates in the synthesis of sulfur- containing heterocycles. 2 They are useful intermediates for drugs and pharmaceuticals. 2b They can be easily transformed in- to various sulfur-containing functional groups. 3 The thiocyanate functionality is useful as a masked sulfanyl group. Therefore, the direct thiocyanation of aromatic systems is of prime importance. As a result, several methods have been developed for the thio- cyanation of arenes using a variety of reagents under certain con- ditions. 4 However, a few reagents such as N-halosuccinimides, ceric ammonium nitrate, acidic K10 clay, iodine/methanol, and oxone have been applied for the thiocyanation of indoles. 5,6 However, these methodologies suffer from drawbacks such as the use of strong oxidizing agents, toxicity of metal thiocya- nates, low yields of products in some cases, less availability or hard preparation of precursors and the formation of mixtures of products as a result of bisthiocyanation especially in case of pyrroles. In addition, many of these methods fail to induce electrophilic thiocyanation on azaindole. In view of the versatil- ity of thiocyanate group in the field of drugs and pharmaceuti- cals, the development of simple, convenient, and highly efficient approaches are desirable. SelectfluorÔ [1-chloromethyl-4- fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)] has recently been introduced commercially as a user-friendly electrophilic fluorinating reagent (Figure 1). 7 It is a commercially available, stable, nonvolatile, nonhy- groscopic, and easy to handle solid and is more widely used for site-selective fluorination of a variety of carbonyl com- pounds. Besides its fluorinating ability, it is also recognized as a convenient mediator of several ‘‘fluorine free’’ functionaliza- tion of organic compounds. 8 These kinds of reactions are based on the fact that F-TEDA-BF 4 has considerable oxidative power, one of the strongest in the family of N–F reagents. But investi- gations taking advantage of this property are still scarce. 9 Furthermore, there have been no examples on the use of SelectfluorÔ for the electrophilic thiocyanation of indoles. In this article, we report a simple, convenient, and efficient protocol for the thiocyanation of N-heterocycles using SelectfluorÔ in acetonitrile. Initially, we attempted the electro- philic thiocyanation of indole (1) with 1 equiv of ammonium thiocyanate (2) using a stoichiometric amount of SelectfluorÔ. N N F Cl + + 2BF 4 - Figure 1. Table 1. Thiocyanation of N-heterocycles with ammonium thiocyanate using SelectfluorÔ N H N H Me N H Et N H O 2 N N H NC N H Br N H MeO N Ph N Me Ph N H N N H N H Substrate N H Ph NEt2 NHEt Entry a b c d e f g i j k l m h n o Time/min 10 10 12 10 10 10 9.0 12 15 15 10 10 15 15 20 Yield% b 95 92 94 93 92 93 96 94 85 88 92 98 89 82 78 N H N H Me N H Et N H O 2 N N H NC N H Br N H MeO N Ph N Me Ph N H N H N H N SCN SCN SCN SCN SCN SCN SCN SCN SCN SCN SCN Product a SCN N H Ph SCN NEt2 NCS NHEt NCS a All products were characterized by 1 H NMR, IR, and mass spectrometry. b Yield refers to pure products after chromatogra- phy. 652 Chemistry Letters Vol.37, No.6 (2008) Copyright Ó 2008 The Chemical Society of Japan