A simple iodination protocol via in situ generated ICl using NaI/FeCl 3 Arasambattu K. Mohanakrishnan, * Chandran Prakash and Neelamegam Ramesh Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India Received 4 November 2005; revised 27 December 2005; accepted 19 January 2006 Available online 14 February 2006 Abstract—A novel iodination of silyl-enol ethers using hitherto unexplored NaI/FeCl 3 system is reported. The procedure has been extended to the iodination of aromatic and hetero aromatic compounds. q 2006 Elsevier Ltd. All rights reserved. 1. Inroduction In general iodination is a relatively difficult process compared to bromination and hence several additives have been used to enhance the rate of iodination reaction. 1 Olah and co-workers reported an iodination of electron-deficient aromatic com- pounds using N-iodosuccinimide in trifluoromethanesulfonic acid. 2 Tour and Kosynkin reported 3 a facile preparation of iodoanilines using a combination of benzyltriethylammonium dichloroiodate and sodium bicarbonate. A novel synthesis of heterocyclic iodo compounds are reported using potassium dichloroiodate under aqueous condition. 4 Colobert and co-workers reported a mild and regioselective iodination of electron-rich aromatics using N-iodosuccinimide in the presence of a catalytic amount of TFA, 5 wherein the iodination was proceeded through the formation of iodotrifluroacetate. Bedekar and co-workers reported 6 an environmentally benign halogenation of aromatic amines, hydrocarbons and naphthols. Recently, Krishnan Mohan et al. reported a regioselective oxiiodination of aromatic compounds using ammonium iodide and oxone. 7 A regioselective bromination of aromatic compounds using LiBr-tetrabutylammonim peroxydisulfate has been observed. 8 Braddock and co-workers reported a similar bromination using LiBr-(diacetoxyiodo)- benzene. 9 Sha and co-workers reported a facile iodination of silyl-enol ether using NaI and m-CPBA. 10 2. Results and discussion In an ongoing project we required a wide variety of a-bromo/iodo ketones for our work on the synthesis of carbocyclic natural products involving a tandem cyclization of a a-carbonyl radical. The required silyl-enol ethers were smoothly prepared via a CuI promoted 1,4-addition of various Grignards to enones. Initially the iodination/ bromination of silyl-enol ether 1a was tried using NIS/NBS without any success. The existing procedure for iodination using NaI/ m-CPBA requires the preparation of dry m-CPBA, which is somewhat difficult and also problematic. Additionally we had a lot of problems with the reproduci- bility of this iodination reaction using NaI/m-CPBA protocol. Considering the synthetic utility of a-iodo ketones we sought to develop a simple procedure, which can iodinate silyl-enol ether in a reasonable yield. We envisioned that FeCl 3 11 could be used for oxidation of the iodide under a mild condition. Our method is based on the generation of electrophilic iodonium ion in situ via the interaction of NaI with FeCl 3 in acetonitrile. As a model reaction silyl-enol ether 1a 12 was reacted with NaI and FeCl 3 (1:2 molar ratio) in acetonitrile at 0 8C to room temperature for 2h followed by usual workup and column chromatographic purification afforded iodo compound 2a in 72% yield, Scheme 1. It should be mentioned that when the iodination was performed with 1 mol equiv of NaI/FeCl 3 (1:1 molar ratio) it was found to be incomplete. Tetrahedron 62 (2006) 3242–3247 0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2006.01.067 O Me TMS TMS CH 3 CN O Me TMS I NaI/FeCl 3 0 °C to rt 2 h 1a 2a Scheme 1. Preparation of iodoketone 2a. Keywords: Iodination; Silyl-enol ether; Iodo cycloalkanones; Iodoindoles. * Corresponding author. Tel.: C91 44 24451108; fax: C91 44 22352494; e-mail: mohan_67@hotmail.com