Heck reaction of b-substituted acrylates in ionic liquids catalyzed by a Pd-benzothiazole carbene complex Vincenzo Calo Á, p Angelo Nacci, Antonio Monopoli, Luigi Lopez and Anna di Cosmo Centro CNR `MISO', Dipartimento di Chimica, Universita Á di Bari, Via Amendola 173-70126 Bari, Italy Received 16 February 2001; revised 24 April 2001; accepted 10 May 2001 Abstract ÐA Pd-catalyst with benzothiazole carbene as ligands allows, in tetrabutylammonium bromide melt as solvent, very fast and ef®cient reactions of haloaromatics with b-substituted acrylates. q 2001 Elsevier Science Ltd. All rights reserved. The Heck reaction and related chemistry occupy a special place among basic types of palladium-catalyzed reactions. 1±3 In most of the papers dedicated to the Heck reaction, only a few examples of its use for the synthesis of trisubstituted ole®ns have been reported. 4±7 As some b,b- diaryl acrylates are useful intermediates for the synthesis of angiotensin II antagonist, 8 platelet activating factors antagonist, 9 and SRS-A antagonists slow-reacting substance of anaphylaxis), 10 the development of an ef®cient process for the Heck arylation of b-substituted acrylates would be of signi®cant utility. Arylation of b-substituted, a,b-unsaturated esters requires harsh reaction conditions, cyclopalladated phosphanes 5,6 or palladium acetate as catalysts, sterically hindered tertiary amines as bases and quaternary ammonium salts as phase-transfer agents in DMF or DMA as solvents 7 have been used. Recently we reported the synthesis 11,12 of a Pd catalyst 1 with benzothiazole carbenes as ligands and its application to an ef®cient Heck synthesis 13 of trans-cinnamates in tetra- butylammonium bromide TBAB) as solvent. S N CH 3 S N CH 3 Pd I I 1 In these reactions, TBAB proved to be an excellent solvent for a fast and stereoselective synthesis of E)-cinnamates. For example, bromobenzene reacted with butyl acrylate and sodium carbonate as base to give E)-butyl cinnamate in only ten minutes and 94% yield. In spite of the increasing interest in the use of ionic liquids 14 as environmentally benign solvents, different hypotheses on their role in catalysis have been reported. 2e This paper reports our results on the synthesis of b-arylsubstituted cinnamates catalyzed by 1 in TBAB as solvent and the probable effects of this solvent in stabilizing the catalyst. 1. Results and discussion Catalyst 1 ef®ciently allows the reaction of various p-substi- tuted bromoaromatics with E)-ethyl cinnamate in TBAB melt as solvent Scheme 1). As shown in Table 1, a procedure employing the catalyst 1 1.5%), sodium formate 3%) as reducing agent and sodium bicarbonate as base in TBAB at 1308C, was very effective in coupling trans-cinnamates with both electron-rich and electron-poor aryl halides with 100% conversion. Even p-nitrochlorobenzene was coupled with ethyl cinnamate as the acceptor, albeit with a lower reaction rate, to give the Tetrahedron 57 2001) 6071±6077 Pergamon TETRAHEDRON 0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII: S0040-402001)00528-2 Keywords: b-aryl cinnamates; ionic liquids; carbenes; Heck reaction. p Corresponding author. Tel.: 139-80-544-2071; fax: 139-80-544-2924; e-mail: calo@chimica.uniba.it + (3÷5%) + TBAB 1 (1.5%) Ph CO 2 Et CO 2 Et Ph Ar CO 2 Et Ph Ar 2-7 Ar X Scheme 1. Arp-CH 3 C 6 H 4 , p-CH 3 OC 6 H 4 , p-CH 3 COC 6 H 4 , a-naphthyl, p-O 2 NC 6 H 4 , p-NCC 6 H 4 ;XCl, Br.