DALTON FULL PAPER J. Chem. Soc., Dalton Trans., 1999, 773–779 773 Reductive coupling of halogenothiophenes and halogenothiazoles catalysed by PdII in a basic alcohol medium Yang Xie,a Geok Kheng Tan,a Yaw Kai Yan,b Jagadese J. Vittal,a Siu Choon Ng *a and T. S. Andy Hor *a a Department of Chemistry, Faculty of Science, National University of Singapore, Kent Ridge, Singapore 119260. E-mail: chmandyh@nus.edu.sg b Division of Chemistry, National Institute of Education, Nanyang Technological University, 469 Bukit Timah Road, Singapore 259756 Received 26th August 1998, Accepted 14th January 1999 A catalytic reductive coupling method has been developed whereby 2- and 3-bromo- and 2-iodothiophenes, 2-bromothiazole and 2-bromofuran are converted into their corresponding bithiophene, bithiazole and bifuran derivatives.The use of a basic alcohol medium favours the reductive coupling pathway over the hydrodehalogenation pathway, which is generally more facile when other reducing agents are used.The catalytic mechanisms are discussed. The syntheses and characterization of the proposed intermediate complexes, trans-[PdBr(C4H3S-C)(PPh3)2] 1, trans-[PdI(C4H3S-C)(PPh3)2] 2 and trans-(N,P)-[{PdBr(m-C3H2NS-C2,N)(PPh3)}2]?��� CHCl3 3 support the proposed mechanism and the catalytic results. Single-crystal X-ray crystallographic structure determinations of 2 and 3 were carried out. Introduction Bithiophenes and their derivatives are important synthetic precursors for conducting polymers1 and biologically active materials.2 Common synthetic methodologies for bithiophenes include Ullmann reaction,3 Grignard coupling 4 and the use of Ni0 as a coupling catalyst.5 While each of these methods has its values, they also have their drawbacks.For example, the Ullmann method is non-selective, requires high temperatures and can produce erratic yields 6 whereas the other two methods, especially the use of nickel(0) catalysts, require careful preparation of the catalysts which are sensitive to air and heat.Recently, a more complex cross-coupling between stannyl and silyl bromothiophenes giving 3,49-disubstituted-2,29-bithiophene has also been reported.7 Recently we reported novel Pd-catalysed hydrodebromination reactions of polybrominated thiophenes which can be used to prepare a range of less accessible bromothiophene isomers.8 A key intermediate in the proposed catalytic mechanism is a palladium–thienyl complex that undergoes rapid hydride transfer prior to elimination of the hydrodebrominated product.8 In this paper we shall describe how we can suppress the hydrodebromination step and promote a bromo–thienyl ligand exchange in an alcohol medium.The success of the latter would pave a way for the facile synthesis of bithiophene through reductive coupling. The reaction conditions and the eVects of the substrates used are described. Results and discussion Catalytic reaction Activity of diVerent catalysts.The palladium catalysts that are able to give a quantitative conversion of 2-bromothiophene under the specified conditions are given in the Experimental section (under Catalytic reactions). 2,29-Bithiophene is invariably the main product and thiophene is the minor one. Trimer 2,29:59,20-terthiophene, oligomers and small amounts of other products are also formed. The formation of these products suggests the occurrence of competing coupling, debromination and polymerization reactions [eqn.(1)]. The complex [PdCl2- (dppf)] is the most eYcient catalyst which gives the highest ratio (bithiophene : thiophene) of products in the shortest time. In spite of some success for nickel and copper complexes in related syntheses, the compounds [Cu(MeCN)4]PF6, [Cu(BH4)(PPh3)2], [NiCl2(dppp)] [dppp = Ph2P(CH2)3PPh2], [Ni{P(OEt)3}4] and [NiCl2(dppf)] exhibit no activity under the current conditions. EVects of diVerent heterocyclic halide substrates and bases.DiVerent substrates viz. 2- and 3-bromothiophene, 2-iodothiophene, 9 2-bromofuran10 and 2-bromothiazole were studied with [PdCl2(dppf)], [Pd(PPh3)4] or Pd(OAc)2 as catalysts (Table 1). Bromothiophenes, 2-iodothiophene and 2-bromofuran give quantitative conversions (entries 1–4 and 7, Table 1). 2-Iodothiophene undergoes dehalogenation more easily. The reactivity of 2-bromothiazole is lower (entries 5 and 6, Table 1). Selectivity for coupling over hydrodehalogenation is best for bromothiophenes.In order to obtain quantitative conversion of 2-bromothiophene and maximum yield of bithiophene, at least one equivalent of NaOH is required per mole of 2- bromothiophene (Table 2). The eVect of an additional quantity of a base on the yield is small, although the rate of reduction is accelerated. The eVects of KOH, pyridine, aniline, DMF, NaOMe, NaOEt, Na2CO3 or NaHCO3 were examined and compared with that of NaOH. Under similar conditions, the eVects of NaOMe, NaOEt and KOH are similar to that of NaOH (entries 1–4, Table 2), whilst the conversion is signifi- cantly lower when the less basic Na2CO3 or NaHCO3 is used (entries 5 and 6, Table 2).There is no reaction with pyridine, aniline and DMF (entries 7–9, Table 2) or when a base is not added (entry 10, Table 2). EVects of alcohols. An alcohol in this reaction serves both as a solvent and reducing agent. It solubilizes the substrates and774 J.Chem. Soc., Dalton Trans., 1999, 773–779 Table 1 The [PdCl2(dppf)], [Pd(PPh3)4] or Pd(OAc)2 catalysed coupling and debromination of diVerent monohalogeno-substrates Entry 1234 c 5 d 6 c 7 Substrate 2-Bromothiophene 3-Bromothiophene 2-Iodothiophene 2-Iodothiophene 2-Bromothiazole 2-Bromothiazole 2-Bromofuran Conversion (%) 100 100 100 100 40 31 100 t/h 2.5 3.5 2 2.5 26 30 5 Product 2,29-Bithiophene 3,39-Bithiophene 2,29-Bithiophene 2,29-Bithiophene 2,29-Bithiazole 2,29-Bithiazole 2,29-Bifuran Yield a (%) 72 74 50 48 20 15 61 Product Thiophene Thiophene Thiophene Thiophene Thiazole Thiazole Furan Yield (%) 23 20 45 43 20 16 34 b:tb 3.1 3.7 1.1 1.1 1.0 1.0 1.8 Conditions: EtOH, 10 cm3; substrate, 2.0 mmol; NaOH, 3.0 mmol; [PdCl2(dppf)], 1 mol%; 60 8C.a Obtained by GC analysis with anthracene as an internal standard. b The mole ratio of the coupling product to debromination product. c [Pd(PPh3)4] as catalyst. d Pd(OAc)2 as catalyst. Table 2 EVects of diVerent bases on the debromination and coupling of 2-bromothiophene Yield a (%) Entry 123456789 10 Base NaOMe NaOH KOH NaOEt Na2CO3 NaHCO3 Pyridine Aniline DMF — Reaction time/h 2.5 2.5 2.5 2.5 2.5 2.5 10 20 30 30 Conversion (%) 100 100 100 100 40 20 0000 Thiophene (t) 30 23 26 27 10 50000 Bithiophene (b) 70 72 71 70 30 15 0000 b:t 2.3 3.1 2.7 2.6 3.0 3.0 Conditions: EtOH, 10 cm3; 2-bromothiophene, 2.0 mmol; base, 3.0 mmol; [PdCl2(dppf)], 1 mol%; 60 8C.a Obtained by GC analysis with anthracene as an internal standard. Table 3 EVects of alcohols on the coupling and debromination of 2-bromothiophene Yield a (%) Entry 12345678 Solvent MeOH EtOH n-PrOH i-PrOH n-BuOH i-BuOH t-BuOH THF Reaction time/h 2.5 2.5 2.5 5.0 5.0 5.0 24 24 Conversion (%) 100 100 64 36 41 11 00 Thiophene (t) 43 23 16 88300 bithiophene (b) 57 72 48 28 33 800 b:t 1.3 3.1 3.0 3.5 4.1 2.7 Conditions: alcohol, 10 cm3; 2-bromothiophene, 2.0 mmol; NaOH, 3.0 mmol; [PdCl2(dppf)], 1 mol%; 60 8C.a Obtained by GC analysis with anthracene as an internal standard. the base. In MeOH and EtOH the reduction is completed after 2.5 h (entries 1 and 2, Table 3) whereas in PrOH and BuOH the conversion is significantly lower (entries 3–7, Table 3). The poorer solubility of bases in these solvents oVers one of the explanations. The steric hindrance of the alcohol also plays a key role. For example, bulky alcohols tend to be less active than their lower homologues (e.g.comparing entries 3 and 4, and 5 and 6, Table 3). The ready availability of b-hydrogen in the alcohol also plays a key role. Thus t-BuOH without an active hydrogen or non-alcohol solvents like toluene, DMSO, 1,4- dioxane and THF show no reducing activity. EVects of temperature and duration. As expected, the reaction rate increases as the temperature is raised from 20 to 78 8C (Fig. 1). The mole ratio of 2,29-bithiophene to thiophene is however fairstant over this temperature range but peaks at ª60 8C.Refluxing conditions (78 8C) lead to more polymerization products and less bithiophene. There is an induction time of 5–10 min before any product is observed (Fig. 2). The light yellow or orange solution gradually turns to dark brown or black during the course of the reaction as the palladium catalyst gradually decomposes upon the consumption of 2-bromothiophene. The product yields peak at 2.5 h duration after which solid precipitates. It is significant that the relative proportion of 2,29-bithiophene to thiophene remains essentially constant through the course of the reaction.This gives a clear indication that neither of these compounds is the precursor for the other in the reaction mechanism. Preparative-scale syntheses of bithiophenes and bifuran Based on the findings listed in Table 2, the coupling products 2,29- and 3,39-bithiophenes and 2,29-bifuran have been synthesized on a preparative scale at 60 8C in the presence of 1 mol% [PdCl2(dppf)] and NaOH in EtOH.The products are isolated by standard methods, giving 2,29- and 3,39-bithiophenes and 2,29-bifuran in 55, 65 and 50% yields respectively. The yields of bithiophenes are similar to those obtained from the Grignard coupling method,4,11 but the present method oVers a simpler procedure with the use of inexpensive reagents. The reaction mechanism The above results allow us to propose two competing mechanisms for reductive coupling and hydrodebromination (Scheme 1).In either mechanism the use of a palladium(0) precursor would enter directly as a palladium(0) catalyst whilstJ. Chem. Soc., Dalton Trans., 1999, 773–779 775 a palladium(II) pre-catalyst can be reduced easily in the presence of NaOH (or other strong base) and alcohol. Both go through an oxidative addition process to give a bromothienyl palladium(II) complex, followed by base-assisted alkoxylation to give an alkoxo thienyl complex.This key intermediate either undergoes a b-H elimination to give a hydride complex, Fig. 1 EVects of temperature on the coupling and hydrodebromination of 2-bromothiophene. Conditions: EtOH, 10 cm3; 2-bromothiophene, 2.0 mmol; NaOH, 3.0 mmol; [PdCl2(dppf)], 1 mol%. The yield was obtained by GC analysis with anthracene as an internal standard. r, Conversion; j, yield of thiophene (t); m, yield of bithiophene (b); ×, b : t. Fig. 2 EVects of reaction time on the coupling and hydrodebromination of 2-bromothiophene at 60 8C.Other conditions and symbols as in Fig. 1. Scheme 1 Proposed catalytic coupling and hydrodebromination mechanisms of 2-bromothiophene. which leads to thiophene through reductive elimination, or bithiophene through deprotonation, oxidative addition and finally reductive elimination. The latter type of mechanism, especially the involvement of a five-co-ordinated palladate,12 has been discussed.13 The observed lower eYciency of the bulkier and less acidic alcohols and those that do not have active b-H is consistent with this mechanism.The higher yield of thiophene in MeOH compared to EtOH (Table 3) is consistent with the higher acidity and the larger number of b-hydrogens of the former. The ease of b-H elimination,14 ligand exchange 15 and reductive elimination 16 on PdII has been well established. We have also substantiated this mechanism by using CD3OD and C2D5OD in the reduction of 2-bromothiophene to 2,29- bithiophene or thiophene; GC-MS analysis showed that all the thiophene is deuteriated.Isolation and characterization of the intermediates In order to have a better understanding of the catalytic mechanism we have isolated the proposed key catalytic intermediates trans-[PdBr(C4H3S-C)(PPh3)2] 1,8 trans-[PdI(C4H3S-C)(PPh3)2] 2 and trans-(N,P)-[{PdBr(m-C3H2NS-C2,N)(PPh3)}2]?��� CHCl3 3 from the stoichiometric reactions between [Pd(PPh3)4] and 2-bromothiophene, 2-iodothiophene and 2-bromothiazole respectively.These compounds were characterized by NMR and X-ray single-crystal crystallography. Complex 1 has recently been reported.8 Complexes 1, 2 and 3 were treated with bromothiophene or bromothiazole and NaOH in EtOH at 60 8C respectively. The GC and GC-MS assays confirmed the generation of bithiophene and thiophene from 1 or 2, and bithiazole and thiazole from 3.† This suggests that these complexes are possible intermediates of the reduction of the respective heterocyclic halides.Structure of trans-[PdI(C4H3S-C)(PPh3)2] 2. Complex 2, similar to 1,8 is a palladium(II) s-thienyl complex with a nearideal square-planar geometry with two phosphines [P(1)–Pd– P(1A) 176.09(7)8] as well as thienyl and iodide [I–Pd–C(1) 180.08] trans to each other (Fig. 3, Table 4). The neutral molecule possesses crystallographically imposed 2-fold rotational Fig. 3 An ORTEP17 plot of the molecular structure of trans- [PdI(C4H3S-C)(PPh3)2] 2 (50% probability ellipsoids).† No vigorous eVort was spent to determine the product ratio of hydrodebromination and coupling products. These ratios would not necessarily be the same as those obtained from the catalytic reactions because the reaction conditions are diVerent. For example, in a catalytic reaction, there is a higher chance for the hydride, e.g. [PdH(C4H3S)L2], to undergo proton abstraction (which leads to bithiophene) than for it to undergo intramolecular elimination of thiophene.776 J.Chem. Soc., Dalton Trans., 1999, 773–779 symmetry. To achieve a strong Pd–thienyl interaction [Pd–C(1) 2.019(7) Å], the thienyl plane makes a dihedral angle of 95.08 with the palladium(II) co-ordination plane to avoid steric interactions with the phenyl groups. There is no indication of h1-S co-ordination or any h2 or h4 metal interaction using the p bonds on the thienyl ring. Metallation at one of the two carbon atoms neighbouring the sulfur gives rise to two C–S bonds of slightly diVerent lengths [C(1)–S(1) 1.696(6) and C(3)–S(1) 1.645(8) Å].The strong trans influence of the thienyl group gives an unusually long Pd–I bond [2.6953(7) Å compared to many other PdII–I bonds, e.g. in the red isomer of [PdI2- (PPhMe2)2] [2.638(3) and 2.619(3) Å],18 yellow isomer of [PdI2(PPhMe2)2] [ 2.59(3) Å],18 trans-[PdI2(PPh3)2] [2.587(1) Å] 19 and [Pd2(m-dppm)2(m-I)(CH3)I]1 [2.577(6) Å].20 The weakness of this Pd–I bond also supports the ready reduction (or Table 4 Selected bond lengths (Å) and angles (8) for trans-[PdI(C4H3SC)( PPh3)2] 2 and trans-(N,P)-[{PdBr(m-C3H2NS-C2,N)(PPh3)}2]? ��� CHCl3 3 (a) trans-[PdI(C4H3S-C)(PPh3)2] 2 Pd(1)–C(1) Pd(1)–P(1) S(1)–C(1) C(1)–C(2) P(1)–C(1A) P(1)–C(1C) C(1)–Pd(1)–P(1) I(1)–Pd(1)–P(1) S(1)–C(1)–Pd(1) C(1)–S(1)–C(3) C(1)–C(2)–C(3D) S(1)–C(3)–C(3D) C(1B)–P(1)–Pd(1) 2.019(7) 2.3618(12) 1.696(6) 1.414(7) 1.831(5) 1.832(5) 88.05(3) 91.95(3) 120.6(2) 92.4(4) 111.1(6) 118.2(3) 119.6(2) Pd(1)–I(1) C(3)–C(3D) S(1)–C(3) C(2)–C(3D) P(1)–C(1B) P(1)–Pd(1)–P(1A) I(1)–Pd(1)–C(1) C(2)–C(1)–Pd(1) S(1)–C(1)–C(2) C(2)–C(3D)–C(3) C(1A)–P(1)–Pd(1) C(1C)–P(1)–Pd(1) 2.6953(7) 1.364(12) 1.645(8) 1.510(3) 1.848(5) 176.09(7) 180.0 127.9(3) 104.3(6) 106.7(4) 113.6(2) 111.2(2) (b) trans-(N,P)-[{PdBr(m-C3H2NS-C2,N)(PPh3)}2]?��� CHCl3 3 A Pd(1)–Br(1) Pd(2)–Br(2) Pd(1)–N(1) Pd(2)–N(2) Pd(1)–C(4) Pd(2)–C(1) Pd(1)–P(1) Pd(2)–P(2) N(1)–C(2) N(1)–C(1) S(1)–C(1) S(1)–C(3) C(2)–C(3) N(2)–C(4) N(2)–C(5) S(2)–C(4) S(2)–C(6) C(5)–C(6) C(4)–Pd(1)–N(1) C(4)–Pd(1)–P(1) N(1)–Pd(1)–P(1) C(4)–Pd(1)–Br(1) N(1)–Pd(1)–Br(1) P(1)–Pd(1)–Br(1) C(1)–Pd(2)–P(2) C(1)–Pd(2)–N(2) N(2)–Pd(2)–P(2) C(1)–Pd(2)–Br(2) P(2)–Pd(2)–Br(2) N(2)–Pd(2)–Br(2) C(1)–N(1)–Pd(1) N(1)–C(1)–Pd(2) Csh;Pd(1) C(4)–N(2)–Pd(2) C(5)–N(2)–Pd(2) S(1)–C(1)–Pd(2) N(2)–C(4)–Pd(1) S(2)–C(4)–Pd(1) 2.4897(8) 2.4725(8) 2.081(4) 2.071(5) 1.981(6) 1.978(6) 2.274(2) 2.266(2) 1.377(7) 1.328(7) 1.718(6) 1.696(7) 1.330(8) 1.315(7) 1.379(7) 1.715(6) 1.707(7) 1.329(9) 84.2(2) 92.1(2) 170.45(1) 170.6(2) 88.92(13) 95.51(5) 93.7(2) 83.4(2) 175.21(14) 171.1(2) 93.09(5) 90.17(13) 117.2(4) 124.5(4) 129.9(4) 118.0(4) 128.1(4) 124.6(3) 124.1(4) 124.5(3) B Pd(1A)–Br(1A) Pd(2A)–Br(2A) Pd(1A)–N(1A) Pd(2A)–N(2A) Pd(1A)–C(4A) Pd(2A)–C(1A) Pd(1A)–P(1A) Pd(2A)–P(2A) N(1A)–C(2A) N(1A)–C(1A) S(1A)–C(1A) S(1A)–C(3A) C(2A)–C(3A) N(2A)–C(4A) N(2A)–C(5A) S(2A)–C(4A) S(2A)–C(6A) C(5A)–C(6A) C(4A)–Pd(1A)–N(1A) C(4A)–Pd(1A)–P(1A) N(1A)–Pd(1A)–P(1A) C(4A)–Pd(1A)–Br(1A) N(1A)–Pd(1A)–Br(1A) P(1A)–Pd(1A)–Br(1A) C(1A)–Pd(2A)–P(2A) C(1A)–Pd(2A)–N(2A) N(2A)–Pd(2A)–P(2A) C(1A)–Pd(2A)–Br(2A) P(2A)–Pd(2A)–Br(2A) N(2A)–Pd(2A)–Br(2A) C(1A)–N(1A)–Pd(1A) N(1A)–C(1A)–Pd(2A) C(2A)–N(1A)–Pd(1A) C(4A)–N(2A)–Pd(2A) C(5A)–N(2A)–Pd(2A) S(1A)–C(1A)–Pd(2A) N(2A)–C(4A)–Pd(1A) S(2A)–C(4A)–Pd(1A) 2.4779(8) 2.4901(8) 2.078(5) 2.082(5) 1.987(6) 1.978(6) 2.269(2) 2.270(2) 1.393(8) 1.320(7) 1.721(6) 1.701(8) 1.344(9) 1.330(7) 1.380(7) 1.719(6) 1.710(6) 1.333(9) 84.9(2) 92.4(2) 174.47(14) 170.8(2) 90.21(13) 91.16(5) 93.4(2) 84.2(2) 170.77(14) 172.3(2) 91.56(5) 91.79(14) 119.1(4) 124.5(4) 128.0(4) 118.1(4) 129.5(4) 124.0(3) 124.9(4) 123.7(3) hydrogen exchange) of 2 with subsequent elimination to give thiophene.Structure of trans-(N,P)-[{PdBr(Ï-C3H2NS-C2,N)(PPh3)}2]? 1–2 CHCl3 3. Elemental analysis suggests that complex 3 contains only one phosphine group per metal atom which is diVerent from that in either 1 or 2.The 1H and 13C NMR data suggest that palladation occurs at the thiazole rings. The single 31P NMR resonance indicates a mononuclear structure or a dinuclear structure with two symmetric PPh3 groups. An array of structures are possible depending on the nuclearity and the relative disposition of the four diVerent donor atoms on the Pd viz. Br, C, N and P. In order to obtain a definitive assignment, an X-ray single-crystal diVraction study was carried out on 3.There are two crystallographically independent molecules A (Fig. 4) and B in the unit cell, but they are similar. They contain a dinuclear structure with two metal atoms bridged by two thiazole groups co-ordinated through C and N. Each PdII is essentially planar with one PPh3 and Br completing the square plane. This structure can also be viewed as a modified “face-toface A-frame” structure. It clearly indicates that the thiazole N is preferentially bonded instead of S and that the phosphine ligand prefers to be trans to the N donor, which has a lower trans influence.To our knowledge, 3 is the first palladium complex of thiazole to be characterized by NMR and single crystal X-ray crystallography. Among the few complexes of thiazole or its derivatives,21 3 is one of two with a dinuclear bridged structure. The other was prepared by electrophilic attack on a thiazole ring with methyllithium.22 An alternative view of the Pd2 structure is a six-membered metal–thiazole ring folded along the Pd ? ? ? Pd hinge at an angle of 88.5(2) (A) or 82.6(2)8 (B).The two co-ordination planes around the metal atoms are significantly skewed from coplanarity to a dihedral angle 87.3(2) (A) or 90.1(2)8 (B). With two phosphines opting to bind selectively trans to the N-donor, it gives a molecular C2 symmetry and the P(2)–Pd(2) ? ? ? Pd(1)– P(1) dihedral angle of 99.3(2) (A) or 96.6(2)8 (B). No direct Pd– Pd bond is envisaged which is consistent with the observed distance of 3.407 (A) or 3.459 Å (B).The average Pd–C (1.981), Pd–N (2.078) and Pd–Br (2.4825 Å) lengths are in agreement with reported values.23 The Pd–Br lengths are intermediate between those in e.g. trans-[PdBr2(PPh3)2] [2.425(1) Å] 24 and trans-dibromobis[2-(2-thienyl)pyridine]palladium [2.431(1) Å] 25 and in e.g. trans-[Pd(Et)(Br)(PMe3)2] [2.554(1) Å] 26 and [PdBr(C5H4N-C2, -C3 or C4)(PEt3)2] [2.522(1)–2.563(3) Å].27 This suggests that the trans influence of thiazole is stronger than bromide but weaker than ethyl or pyridyl.The Pd–P lengths (average 2.270 Å) on the contrary are slightly shorter Fig. 4 An ORTEP plot of the molecular structure of one of the two independent molecules (A) in the asymmetric unit of trans-(N,P)- [{PdBr(m-C3H2NS-C2,N)(PPh3)}2] 3 (50% probability ellipsoids).J. Chem. Soc., Dalton Trans., 1999, 773–779 777 than those found elsewhere (2.306–2.350 Å).23 Palladation imparts a very slight structural or geometric eVect on the thiazolyl group when compared with free thiazole.28 The isolation of complex 3 suggests that a dinuclear structure could also exist in equilibrium with mononuclear intermediates in the catalytic cycles for reductive dehalogenation or coupling of difunctional heterocycles.The higher stability of dinuclear complexes could explain the lower reactivity of bromothiazole compared to halogenothiophenes. Current research in our laboratory is directed at the isolation of the reaction intermediates of other multifunctional heterocycles and the study of their synthetic utilities.Experimental General All reactions were performed using standard Schlenk techniques. All solvents were degassed before use. Reagent-grade toluene and diethyl ether were distilled from sodium– benzophenone under nitrogen. The compound Pd(OAc)2, 2- and 3-bromothiophene and 2-bromothiazole were commercial products used without further purification. 2-Iodothiophene, 9 2-bromofuran,10 [PdCl2(PPh3)2],29 [PdCl2(dppf)],30 [Pd- (PPh3)4],31 [PdCl2(dppr)],‡32 [Pd(dba)2],‡33 [PdCl2(MeCN)2],34 [NiCl2(dppp)],35 [NiCl2(dppf)],36 [Ni{P(OEt)3}4],37 [Cu(Me- CN)4]PF6 38 and [Cu(BH4)(PPh3)2] 39 were prepared according to published procedures. GC and GC-MS Gas chromatographic analyses were carried out on a Hewlett- Packard (HP) 5890 Series II Plus gas chromatograph with an HP-1 capillary column (25 m × 0.32 mm, id, 0.25 mm phase thickness) with a flame ionization detection system.A split/ splitless injector was used in the splitless mode. Nitrogen was used as the carrier gas and the flow rate was 1.28 cm3 min21. The temperatures for injector and detector were 280 and 300 8C respectively. The temperature programme for the analysis of the catalytic reaction mixture was as follows: initial oven temperature held at 50 8C for 5 min, increased to 300 8C at a rate of 10 8C min21, final temperature held for 2 min.For mass spectrometric analysis of the reaction mixture a Hewlett-Packard 5890 Series I gas chromatograph equipped with an HP 5988A mass spectrometer installed with a Continuous Dynode Electron Multiplier (CDEM) was used. The ionization mode was EI. The system was operated with an HP 59970 MS ChemStation system and an NBS library database (version 3.1). The column used was a 25 m × 0.32 mm, id (0.25 mm phase thickness) HP-5 capillary column. Helium was the carrier gas and the flow rate was 1.29 cm3 min21.The temperatures for the injector, transfer line, and ion source were 280, 280 and 200 8C respectively. The mass spectrometer was tuned to perfluorotributylamine (PFTBA). The following temperature programme was used: 50 8C held for 5 min, followed by a linear increase (10 8C min21) to a final temperature of 280 8C, held for another 10 min. NMR analysis The NMR spectra were acquired on a Bruker ACF 300 spectrometer, 1H spectra being referenced to the internal reference SiMe4 with CDCl3 as solvent, 13C to the same solvent and 31P internally relative to the deuterium lock signal using the SR Command of Standard Bruker Software with the standard 85% H3PO4–D2O. Elemental analyses were carried out by the Microanalytical Laboratory of the Chemistry Department at National University of Singapore.‡ dppr = 1,19-Bis(diphenylphosphino)ruthenocene; dba = dibenzylideneacetone. Catalytic reactions The catalytic reactions were carried out under an atmosphere of nitrogen using standard Schlenk techniques.Magnetic stirring was used for all reactions. A typical procedure was as follows: 10 cm3 of degassed alcohol, 20 mmol of substrate and 30 mmol of NaOH were added to a Schlenk flask which was connected to the nitrogen gas supply and a reflux condenser. The flask was then flushed with nitrogen gas and the rate of gas flow monitored by means of a bubbler fitted at the neck of the reflux condenser.The solution was stirred for ª5 min before a 1 mol% amount of the catalyst was added. The flask was immersed in an oil-bath maintained at 60 8C for a designated duration with stirring. The reaction mixtures were analysed by GC with anthracene as an internal standard. The products were assayed by gas chromatography, identified by GC-MS analysis and confirmed by comparisons with authentic samples. Debromination of 2-bromothiophene was tested by ten palladium {viz.Pd(OAc)2, Pd(OAc)2 1 L (L = PPh3 or dppe), [Pd(dba)2], [Pd(dba)2] 1 dppe, [PdCl2L] (L = 2PPh3, 2MeCN, dppf or dppr), [Pd(PPh3)4]} and other copper and nickel catalytic systems. Only the palladium systems showed any measurable activities. The complex [PdCl2(dppf)] was the best performer in terms of the time taken for completion (2��� h) and the yields of 2,29-bithiophene (b) (72%) with respect to thiophene (t) (23%), which gives a b: t ratio of 3.1; [PdCl2(PPh3)], [PdCl2(dppf)] and [Pd(PPh3)4] also showed a reasonable b : t ratio of 2.7–2.8 : 1 taking 3 h for completion.Other palladium systems were less satisfactory (b : t 2.2–2.4 : 1; 3–6 h). Preparative-scale syntheses 2,29-Bithiophene. An oxygen-free mixture of 2-bromothiophene (8.1 g, 50 mmol) and NaOH (3.0 g, 75 mmol) in EtOH (100 cm3) was stirred at 60 8C under nitrogen for about 10 min to allow NaOH to dissolve. The complex [PdCl2(dppf)] (0.36 g, 0.5 mmol) was then added and the mixture stirred continuously at 60 8C for 2.5 h.Upon completion of reaction (monitored by TLC) the mixture was evaporated to about 20 cm3 and the solid was separated by filtration. Ice–water was then added to the filtrate to precipitate 2,29-bithiophene, which was collected by filtration to give a yield of 50%, mp 31–33 8C. Owing to the low melting point of 2,29-bithiophene, which made filtration diYcult, the filtrate can be treated alternatively by removing the solvent and distilling the crude compound in vacuo.The main fraction which distilled at bp 87–88 8C (1.5 mmHg) (lit.,4 bp 144 8C, 25 mmHg) was collected, giving pure 2,29-bithiophene (4.5 g, 55%). dH(CDCl3) 7.20 (dd, 2 H, J = 5.1, 1.2), 7.17 (dd, 2 H, J = 3.6, 1.2) and 7.01 (dd, 2 H, J = 5.1, 3.6 Hz). m/z 166 (M1, 100%). 3,39-Bithiophene. An oxygen-free mixture of 3-bromothiophene (8.1 g, 50 mmol) and NaOH (3.0 g, 75 mmol) in EtOH (100 cm3) was stirred at 60 8C under nitrogen for about 10 min to allow NaOH to dissolve.The complex [PdCl2(dppf)] (0.36 g, 0.5 mmol) was then added. The mixture was stirred continuously at 60 8C for 2.5 h. Upon completion of reaction (monitored by TLC) the mixture was evaporated to about 20 cm3 and the solid separated by filtration. Ice–water was then added to the filtrate to precipitate 3,39-bithiophene which was collected on a filter in 65% yield (5.3 g), mp 131–133 8C.40 dH(CDCl3) 7.38 (m, 2 H) and 7.35 (m, 4 H). m/z 166 (M1, 100%). 2,29-Bifuran.An oxygen-free mixture of 2-bromofuran (2.9 g, 20 mmol) and NaOH (1.4 g, 35 mmol) in EtOH (50 cm3) was stirred at 60 8C under nitrogen for about 10 min to allow NaOH to dissolve. The complex [PdCl2(dppf)] (0.144 g, 0.2 mmol) was then added. The mixture was stirred continuously at 60 8C for778 J. Chem. Soc., Dalton Trans., 1999, 773–779 Table 5 Crystallographic data and refinement details for trans-[PdI(C4H3S-C)(PPh3)2] 2 and trans-(N,P)-[{PdBr(m-C3H2NS-C2,N)(PPh3)}2]? ��� CHCl3 3 Molecular formula M Colour and habit Crystal size/mm Crystal system Space group T/K a/Å b/Å c/Å a/8 b/8 g/8 F(000) V/Å3 Z m/mm21 Dc/g cm23 Reflections collected Independent reflections Final R, R9 indices (observed data) Goodness of fit Largest diVerence peak and hole/e Å23 2 C40H33IP2PdS 840.96 Yellow prism 0.25 × 0.23 × 0.13 Orthorhombic Pbcn 293(2) 19.4193(4) 10.9234(3) 16.4094(3) 1672 3480.84(14) 4 1.600 1.605 20238 4377 (Rint = 0.0227) 0.0541, 0.1050 1.252 0.674 and 20.926 3 C42H34Br2N2P2Pd2S2?��� CHCl3 1125.58 Colourless block 0.25 × 0.10 × 0.08 Triclinic P1� 293(2) 13.2315(2) 16.6131(4) 20.0065(4) 88.055(1) 83.110(1) 86.919(1) 2214 4358.0(2) 4 2.953 1.716 25796 19089 (Rint = 0.0231) 0.0567, 0.0983 1.064 0.976 and 20.770 2.5 h.Upon completion of reaction (monitored by TLC) the mixture was evaporated to about 10 cm3 and the solid separated by filtration. The solvent was removed from the filtrate and the crude product distilled in vacuo. The main fraction which distilled at bp 65–67 8C (11 mmHg) (lit.,41 bp 63–64 8C, 11 mmHg) was collected, giving pure 2,29-bifuran (1.34 g, 50%).dH(CDCl3) 6.10 (dd, 2H), 7.01 (d, 2 H, J = 1.1) and 7.23 (d, 2 H, J = 3.3 Hz). m/z 134 (M1, 100%). trans-[PdI(C4H3S-C)(PPh3)2] 2. A mixture of [Pd(PPh3)4] (1.156 g, 1.0 mmol) and 2-iodothiophene (0.252 g, 1.2 mmol) in toluene (20 cm3) was deoxygenated and stirred overnight in a 50 cm3 Schlenk flask under argon at room temperature (r.t.).The resultant yellow solution was evaporated to dryness in vacuo. The solid residue was triturated with Et2O and the ether solution discarded. The washing was repeated twice to remove PPh3 and the residual product purified further by recrystallization from chloroform–hexane. Complex 2 was obtained as yellow crystals (0.71 g, 86%), mp ª180 8C (decomp.) (Found: C, 57.1; H, 3.7; I, 15.0; P, 7.0; Pd, 12.2; S, 3.5. C40H33IP2PdS requires C, 57.1; H, 3.9; I, 15.1; P, 7.4; Pd, 12.7; S, 3.8%); dH(CDCl3) 7.53 (m, 12 H), 7.28 (t, 18 H, PPh3), 6.82 (d, 1 H, 3JHH = 4.82, H3– Pd), 6.33 (dd, 1 H, H4–Pd) and 5.89 (d, 1 H, 3JHH = 3.25 Hz, H5–Pd); dP(CDCl3) 21.9; dC(CDCl3) 134.7 (t, 3JCP = 6.3, Co–P), 130.4 (s, Cp–P), 130.0 (t, 2JCP = 24.3, Ci–P), 127.7 (t, 4JCP = 5.3, Cm–P), 146.1 (t, 2JCP = 8.3 Hz, C1–Pd), 126.9 (s, C3–Pd), 128.3 (s, C4–Pd) and 132.0 (s, C5–Pd).trans-(N,P)-[{PdBr(Ï-C3H2NS-C2,N)(PPh3)}2]?1– 2CHCl3 3. A mixture of [Pd(PPh3)4] (0.58 g, 0.5 mmol) and 2-bromothiazole (0.41 g, 2.5 mmol) in toluene (30 cm3) was deoxygenated and stirred overnight in a 50 cm3 Schlenk flask under argon at r.t.The resultant yellow suspension was evaporated to about 5 cm3 in vacuo. The pale solid residue was filtered oV and washed with ethanol (2 × 5 cm3) and then Et2O (2 × 5 cm3). The solid was recrystallized from a CHCl3–EtOH mixture. Complex 3 was obtained as colourless crystals (0.46 g, 82%), mp ª265 8C (decomp.) (Found: C, 45.2; H, 3.4; Br, 14.0; Cl, 4.5; N, 2.6; P, 5.8; Pd, 17.9; S, 5.3.C42H34Br2N2P2Pd2S2?��� CHCl3 requires C, 45.4; H, 3.1; Br, 14.2; Cl, 4.7; N, 2.5; P, 5.5; Pd, 18.9; S, 5.7%); dH(CDCl3) 7.80 (m, Ho–P, 12 H), 7.34 (m, Hm–P, Hp–P, 18 H), 6.87 (d, 2H, 3JHH = 3.54, H4,49–Pd) and 7.88 (d, 2 H, 3JHH = 3.54 Hz, H5,59–Pd); dP(CDCl3) 30.2 (s, PPh3); dC(CDCl3) 134.8 (d, 3JCP = 11.4, Co–P), 130.8 (d, 2JCP = 44.6, Ci–P), 130.7 (s, Cp–P), 128.5 (t, 4JCP = 11.2, Cm–P), 183.8 (d, 2JCP = 2.7, C2,29–Pd), 142.5 (s, C5,59–Pd) and 120.0 (d, 2JCP = 5.4 Hz, C4,49–Pd).X-Ray crystallography Single crystals of complex 2 were grown by the diVusion method with hexane layered onto the sample solution in CHCl3, while those of 3 were grown by slow evaporation of a MeOH–CHCl3 mixture at r.t. The data crystals were mounted at the end of glass fibres. The diVraction experiments were carried out ractometer with a Mo-Ka sealed tube at 23 8C. Preliminary cell constants were obtained from 45 frames (width of 0.38 in w) of data.Final cell parameters were obtained by global refinements of reflections obtained from integration of all the frame data. The software SMART42 was used for collecting frames of data, indexing reflections and determination of lattice parameters, SAINT42 for integration of intensity of reflections and scaling, SADABS43 for absorption correction and SHELXTL44 for space group and structure determination, refinements, graphics and structure reporting.For 2, the space group Pbcn was determined unambiguously from the systematic absences. For Z = 4, there is a crystallographically imposed 2-fold symmetry present in the neutral molecule and the 2-fold rotation axis runs through Pd(1), I(1) and C(1) of thiophene. As a consequence, the thiophene ligand is disordered which has been modelled successfully. All the non-hydrogen atoms were assigned anisotropic thermal parameters and refined in the least-squares cycles.Riding models were used to place the hydrogen atoms. For 3 the space group is P1� . For Z = 4 there are two independent molecules present in the asymmetric unit. In the Fourierdi Verence routine a chloroform molecule was located and the chlorine atoms were found to be disordered along the C3 axis. Two disordered structures were resolved (occupancies 0.55/ 0.45) and included in the refinement cycles. The occupancy factors were obtained from the ratios of the electron densities of Cl atoms in the Fourier-diVerence map and not refined.Common isotropic thermal parameters were refined for each group and an isotropic thermal parameter was refined for the carbon atom of the solvate. Anisotropic thermal parameters were refined for all the non-hydrogen atoms in the neutral molecule. Riding models were used to place the hydrogen atoms in the neutral molecule. DiVerences in the orientations of the phenyl rings were found when the two independent moleculesJ.Chem. Soc., Dalton Trans., 1999, 773–779 779 were superimposed onto each other. The program MISSYM45 did not find any additional symmetry in the crystal lattice. The crystallographic data and refinement details are shown in Table 5. CCDC reference number 186/1316. Acknowledgements We are grateful to the National University of Singapore (NUS) (RP 960655) for support of this work. We thank the technical staV in the Department of Chemistry at NUS for assistance and T.Y. W. Chia for some preliminary work. Technical assistance from J. S. L. Yeo and Y. P. Leong is appreciated. Y. X. thanks NUS for a scholarship award. References 1 B. Krische, J. Hellberg and C. Lilja, J. Chem. Soc., Chem. Commun., 1987, 1476; J. Tanguy, A. Pron, M. Zargoska and I. Kulszewicz- Bajer, Synth. Met., 1991, 45, 81; M. Zargoska, I. Kulszewicz-Bajer, A. Pron, I. Firlej, P. Bernier and M. Galtier, Synth. Met., 1991, 45, 385; J. Roncali, Chem.Rev., 1992, 92, 711; 1997, 97, 173; S. C. Ng, H. S. O. Chan, H. H. Huang and R. S. H. Seow, J. Chem. Res., 1996, (S) 232; (M) 1285; S. C. Ng, H. S. O. Chan and P. Miao, J. Mater. Sci. Lett., 1997, 16, 1170; H. S. O. Chan, S. C. Ng, R. S. H. Seow and M. J. G. Moderscheim, J. Mater. Chem., 1992, 2, 1135. 2 R. Taylor, in Thiophene and Its Derivatives, ed. S. Gronowitz, Wiley, New York, 1985, vol. 44 (part 1), ch. 3. 3 J. W. Sease and L. Zechmeister, J. Am. Chem. Soc., 1947, 69, 270. 4 K.Tamao, S. Kodama, I. Nakajima and M. Kumada, Tetrahedron, 1982, 38, 3347. 5 M. F. Semmelhack, P. M. Helquist and L. D. Jones, J. Am. Chem. Soc., 1971, 93, 5908. 6 H. Wynberg and A. Logothetis, J. Am. Chem. Soc., 1956, 78, 1958. 7 L. Antolini, F. Goldoni, D. Iarossi, A. Mucci and L. Schenetti, J. Chem. Soc., Perkin Trans. 1, 1997, 1957. 8 Y. Xie, S. C. Ng, T. S. A. Hor and H. S. O. Chan, J. Chem. Res. (S), 1996, 150; Y. Xie, S. C. Ng, B. Wu, F. Xue, T. C. W. Mak and T.S. A. Hor, J. Organomet. Chem., 1997, 531, 175; Y. Xie, B. M. Wu, F. Xue, S. C. Ng, T. C. W. Mak and T. S. A. Hor, Organometallics, 1998, 17, 3988. 9 H. Y. Lew and C. R. Noller, Org. Synth., 1963, Coll. Vol. 4, 545. 10 R. Sornay, J. M. Meunier and P. Fournari, Bull. Soc. Chim. Fr., 1971, 990. 11 A. E. Lipkin, J. Gen. Chem. USSR, 1963, 33, 188; S. Gronowitz and H.-O. Karlsson, Ark. Kemi, 1960, 17, 89; K. Tamao, K. Sumitani, Y. Kiso, M. Zembayashi, A. Fujioka, K. Kodama, I.Nakajima, A. Minato and M. Kumada, Bull. Chem. Soc. Jpn., 1976, 49, 1958; D. G. Morrell and J. K. Kochi, J. Am. Chem. Soc., 1959, 84, 1421. 12 C. Amatore, A. Jutand and A. Suarez, J. Am. Chem. Soc., 1993, 115, 9531. 13 E. Negishi and F. Liu, in Metal-Catalyzed Cross-Coupling Reactions, eds. F. Diederich and P. J. Stang, Wiley-VCH, Weinheim, 1998, ch. 1, p. 34. 14 F. Ozawa, T. I. Son, S. Ebina, K. Osakada and A. Yamamoto, Bull. Chem. Soc. Jpn., 1981, 54, 1868; W. De Gaaf, J.Boersma, W. J. J. Smeets, A. L. Spek and G. van Koten, Organometallics, 1989, 8, 2907; F. Ozawa, I. Takashi and A. Yamamoto, J. Am. Chem. Soc., 1980, 102, 6457. 15 F. Balegroune, P. Braunstein, T. M. G. Carneiro, D. Grandjean and D. Matt, J. Chem. Soc., Chem. Commun., 1989, 582; F. Balegroune, D. Grandjean, D. Lakkis and D. Matt, J. Chem. Soc., Chem. Commun., 1992, 1084; P. Braunstein, T. M. G. Carneiro, D. Matt, F. Balegroune and D. Grandjean, Organometallics, 1989, 8, 1737. 16 R. Sustmann, J. Lau and M. Zipp, Recl. Trav. Chim. Pays-Bas, 1986, 105, 356; R. Sustmann and J. Lau, Chem. Ber., 1986, 119, 2531. 17 C. K. Johnson, ORTEP, Report ORNL 5138, Oak Ridge National Laboratory, Oak Ridge, TN, 1976. 18 N. A. Bailey and R. Mason, J. Chem. Soc. A, 1968, 2594. 19 T. Debaerdemaeker, A. Kutoglu, G. Schmid and L. Weber, Acta Crystallogr., Sect. B, 1973, 29, 1283. 20 M. M. Olmstead, J. P. Farr and A. L. Balch, Inorg. Chim. Acta, 1981, 52, 47. 21 E. S. Raper, Coord.Chem. Rev., 1994, 129, 91; H. G. Raubenheimer, F. Scott, S. Cronje, P. H. van Rooyen and K. Psotta, J. Chem. Soc., Dalton Trans., 1992, 1009; S. K. Hadjikakou, P. Aslanidis, P. Karagiannidis, D. Mentzafos and A. Terzis, Polyhedron, 1991, 10, 935; Inorg. Chim. Acta, 1991, 186, 199; L. P. Battaglia, A. B. Corradi, M. R. Cramarossa, I. M. Vezzosi and J. G. Giusti, Polyhedron, 1993, 12, 2235; R. Castro, J. A. Garcia-Vazquez, J. Romero, A. Sousa, C. A. McAuliVe and R. Pritchard, Polyhedron, 1993, 12, 2241. 22 G. Boche, C. Hilf, K. Harms, M. Marsch and J. C. W. Lohrenz, Angew. Chem., Int. Ed. Engl., 1995, 34, 487. 23 K. Nakatsu, K. Kinoshita, H. Kanda, K. Isobe, Y. Nakamura and S. Kawaguchi, Chem. Lett., 1980, 913. 24 Y. Xie, S. C. Ng, T. C. W. Mak and T. S. A. Hor, unpublished results. 25 T. J. Giordano, W. M. Butler and P. G. Rasmussen, Inorg. Chem., 1978, 17, 1917. 26 K. Osakada, Y. Ozawa and A. Yamamoto, J. Chem. Soc., Dalton Trans., 1991, 759. 27 K. Isobe, E. Kai, Y. Nakamura, K. Nishimoto, T. Miwa, S. Kawaguchi, K. Kinoshita and K. Nakatsu, J. Am. Chem. Soc., 1980, 102, 2475. 28 L. Nygaard, E. Asmussen, J. H. Hoeg, R. C. Maheshwari, C. H. Nielsen, I. B. Petersen, J. Rastrup-Andersen and G. O. Soerensen, J. Mol. Struct., 1971, 8, 225. 29 R. F. Heck, in Palladium Reagents in Organic Syntheses, Academic Press, New York, 1985, ch. 1, p. 18. 30 T. Hayachi, M. Konishi, Y. Kobori, M. Kumada, T. Higuchi and K. Hirotsu, J. Am. Chem. Soc., 1984, 106, 158. 31 D. R. Coulson, Inorg. Synth., 1972, 13, 121. 32 J. M. Brown and P. J. Guiry, Inorg. Chim. Acta, 1994, 220, 249. 33 M. F. Rettig and P. M. Maitlis, Inorg. Synth., 1977, 17, 134. 34 J. R. Doyle, P. E. Slade and H. B. Jonassen, Inorg. Synth., 1960, 6, 218. 35 G. Booth and J. Chatt, J. Chem. Soc., 1965, 3238. 36 B. Corain, B. Longato, G. Favero, D. Ajò, G. Pilloni, U. Russo and F. R. Kreissl, Inorg. Chim. Acta, 1989, 157, 259. 37 M. Meier and F. Basolo, Inorg. Synth., 1990, 28, 104. 38 G. J. Kubas, Inorg. Synth., 1979, 19, 90. 39 T. N. Sorrell and P. S. Pearlman, J. Org. Chem., 1980, 45, 3449. 40 E. Khor, S. C. Ng, H. C. Li and S. Chai, Heterocycles, 1991, 32, 1805. 41 R. C. Larock and J. C. Bernhardt, J. Org. Chem., 1977, 42, 1680. 42 SMART & SAINT Software Reference Manuals, Version 4.0, Siemens Energy & Automation, Inc., Analytical Instrumentation, Madison, WI, 1996.3 G. M. Sheldrick, SADABS, a Software for Empirical Absorption Correction, University of Göttingen, 1996. 44 SHELXTL Reference Manual, Version 5.03, Siemens Energy & Automation, Inc., Analytical Instrumentation, Madison, WI, 1996. 45 Y. LePage, J. Appl. Crystallogr., 1987, 20, 264. Paper 9/00419J