Synthesis of highly substituted m-chlorophenolic biaryls by chlorine substituent-promoted Diels–Alder reaction of 2-aryl-3-chlorofurans Ram N. Ram * , Neeraj Kumar Department of Chemistry, Indian Institute of Technology, Delhi, Hauz Khas, New Delhi 110016, India article info Article history: Received 17 May 2008 Received in revised form 14 July 2008 Accepted 15 July 2008 Available online 18 July 2008 Keywords: 3-Chlorofurans Diels–Alder reaction Dimethyl acetylenedicarboxylate Chlorophenolic biaryls Chlorine effect abstract Chlorine substituent-promoted Diels–Alder reaction of 2-aryl-3-chlorofurans with dimethyl acetylene- dicarboxylate at 100  C afforded highly substituted m-chlorophenolic biaryls in 59–78% yields. Ó 2008 Published by Elsevier Ltd. 1. Introduction Biaryl structural unit is present in several bioactive natural products, 1 pharmaceuticals, 2 ligands of organometallic catalysts, 3 optoelectronics materials 4 and supramolecular assemblies. 5 A large number of biaryls in these applications are phenolic biaryls. Several modern methods for the preparation of biaryls are available, which involve transition metal-catalyzed cross-coupling of aryl halides (or less frequently pseudo-halides) with an aryl organometallic. 6 Phenolic biaryls may be prepared by these methods directly from iodophenols. However, the less reactive but more easily accessible chloro or bromophenols may be problematic unless the phenolic group is protected in an additional step because the halogen atom is deactivated further by the hydroxylate donor group formed under the basic conditions employed. 7 Therefore, direct biaryl coupling of phenols have generally been realized by their oxidative cou- pling, 6g,8 which is believed to be the Nature’s way of biaryl syn- thesis, 9 although some satisfactory Suzuki coupling procedures with bromophenols 7,10 and a few methods involving direct aryla- tion of phenols with aryl halides 11 have recently been reported. An alternative approach to phenolic biaryls involving Diels–Alder re- action of 1-aryl-3-siloxybuta-1,3-dienes with acetylenic dieno- philes followed by aromatization of the cycloadduct with DDQ has also been reported. 12 This approach to general biaryl synthesis has received renewed interest in recent times because it has the advantage of atom economy, does not generate waste stream and would not be complicated by regiochemical problem in the syn- thesis of biaryls containing a nucleofugal group, such as bromo or iodo. 13 Diels–Alder reaction of furans with acetylenic dienophiles would furnish phenolic biaryls either directly or by acid-catalyzed ring-opening of the intermediate oxabicycloheptadiene adduct. 14 However, there are only a few reports on the synthesis of phenolic biaryls through Diels–Alder reaction of 2-aryl furans, which affor- ded some simple phenolic biaryls in low to moderate yields along with oxabicyloheptadiene adducts in many cases and required long reaction time and/or Lewis acid catalysis. 15 This is probably because the efficiency of furan Diels–Alder reaction is generally afflicted by the low reactivity of a furano diene due to its aromaticity and re- versibility of the reaction due to the formation of strained oxabi- cyclo adduct. Therefore, the need to improve this synthetically versatile reaction 16 cannot be over-emphasized. Therefore, several improved procedures that involve catalysis by Lewis acids 17 have been developed. High pressure, 18 microwave heating 19 and ultra- sound 20 have also been reported to have beneficial effects on the reaction. An alternative strategy in this respect is to use a halo- furan. Experimental results show that a halogen substituent on furan ring enhances the rate and efficiency of furan Diels–Alder reaction and decreases its reversibility. 21 This, the so-called ‘halo- gen effect’ has recently been validated by theoretical calculations also. 22 An added advantage of this approach is that the halogen functionality in the adduct can be elaborated further or easily removed. Recently, we reported the synthesis of some 2-aryl-3-chloro- furans by using CuCl/bpy-catalyzed halogen atom transfer radical * Corresponding author. Tel.: þ91 11 26591508; fax: þ91 11 26582037. E-mail address: rnram@chemistry.iitd.ernet.in (R.N. Ram). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd. doi:10.1016/j.tet.2008.07.050 Tetrahedron 64 (2008) 10267–10271