Iron(III)-Catalyzed Peroxide-Mediated C-3 Functionalization of Flavones Bilal Ahmad Mir, a Arghya Banerjee, a Sourav Kumar Santra, a Suresh Rajamanickam, a and Bhisma K. Patel a, * a Department of Chemistry, Indian Institute of Technology, Guwahati, North Guwahati – 781 039, Assam, India Fax: (+ 91)-361-2690-9762; e-mail: patel@iitg.ernet.in Received: May 28, 2016; Revised: August 10, 2016; Published online: September 20, 2016 Supporting information for this article can be found under: http://dx.doi.org/10.1002/adsc.201600565. Abstract: An iron(III)-catalyzed C-3 functionaliza- tion of flavones has been achieved using tert-butyl peroxybenzoate (TBPB)/potassium persulphate (K 2 S 2 O 8 ) oxidant combinations with a suitable sol- vent. In the presence of iron(III)/tert-butyl peroxy- benzoate/potassium persulphate, the reaction of fla- vones in cycloalkanes afforded exclusive C-3 cyclo- alkylation via C sp 2 –C sp 3 coupling, whereas the sol- vent N,N-dialkylformamide provided C-3 amidation via C sp 2 –C sp 2 coupling. Under identical reaction con- ditions just by switching the solvent to chloroben- zene, C-3 methylated flavones were obtained where tert-butyl peroxybenzoate (TBPB) served as the source of the methyl group. Keywords: C–H functionalization; cycloalkylation; flavones; formamidation; iron catalysis; methyla- tion Transition metal-catalyzed C–H functionalization has undergone a renaissance in the past decade for the construction of carbon–carbon (C–C) and carbon–het- eroatom (C–X) bonds. [1] In this context cross dehy- drogenative coupling (CDC) protocols have emerged as a promising and powerful tool towards the forma- tion of C sp 2 –C sp ,C sp –C sp 2 and C sp 2 –C sp 2 bonds. [2] In recent times this CDC protocol has even made prog- ress for the formation of C sp 3 –C bonds. [3] In this con- text cycloalkanes have been employed for CDC reac- tions in the absence [4a,b] or presence of transition metal catalysts [4c–g] albeit with limited examples. Ali- phatic C sp 3 –H bonds are the most available natural re- source. Thus, methodologies for the direct functionali- zation of aliphatic C sp 3 –H bonds will expand the syn- thetic toolbox, allowing access to value-added prod- ucts with various important applications. Flavone is an important structural motif, present in many natural products and pharmaceutical molecules having a wide range of biological and pharmaceutical applications. [5] Thus, any further derivatization on this moiety may generate potentially important candi- dates. To date there are many examples where chro- mones have been employed as the coupling partner for regioselective C-2 functionalization (b-functionali- zation) with arenes, [6a,b] cycloalkanes or cyclic ethers using transition metals, [6c] hypervalent iodine [4b] or under metal-free conditions [5e] (Scheme 1). However, Scheme 1. Various routes for C-2/C-3 functionalizations of chromones/flavones. Adv. Synth. Catal. 2016, 358, 3471 – 3476  2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 3471 UPDATES DOI: 10.1002/adsc.201600565 16154169, 2016, 21, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adsc.201600565 by Jawaharlal Nehru Centre For, Wiley Online Library on [01/02/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License