Supported palladium catalysis using a heteroleptic 2-methylthiomethyl- pyridine–N,S–donor motif for Mizoroki–Heck and Suzuki–Miyaura coupling, including continuous organic monolith in capillary microscale flow-through mode Roderick C. Jones a, * , Allan J. Canty a, * , Jeremy A. Deverell a, b , Michael G. Gardiner a , Rosanne M. Guijt b , Thomas Rodemann c , Jason A. Smith a , Vicki-Anne Tolhurst a a School of Chemistry, University of Tasmania, Private Bag 75, Hobart TAS 7001, Australia b Australian Centre for Research on Separation Science (ACROSS), Private Bag 75, Hobart TAS 7001, Australia c Central Science Laboratory (CSL), University of Tasmania, Private Bag 74, Hobart TAS 7001, Australia article info Article history: Received 16 April 2009 Received in revised form 24 June 2009 Accepted 2 July 2009 Available online 8 July 2009 Keywords: Catalysis Supported catalysis Monolith Flow-through microreactor Pyridine Methylthiomethylpyridine abstract Flow-through catalysis utilising (2-methylthiomethylpyridine)palladium(II) chloride species covalently attached to a macroporous continuous organic polymer monolith synthesised within fused silica capillaries of internal diameter 250 mm is described, together with related studies of ground bulk monolith compared with supported catalysis on Merrifield and Wang beads and homogeneous catalysis under identical con- ditions to bulk supported catalysis. The monolith substrate, poly(chloromethylstyrene-co-divinylbenzene), has a backbone directly related to Merrifield and Wang resins. The homogeneous precatalyst PdCl 2 (L 2 ) (L 2 ¼4-(4-benzyloxyphenyl)-2-methylthiomethylpyridine) contains the benzyloxyphenyl group on its pe- riphery as a model for the spacer between the ‘PdCl 2 (NwS)’ centre and the polymer substituent of the resins and monolith. Suzuki–Miyaura and Mizoroki–Heck catalysis exhibit anticipated trends in reactivity with variation of aryl halide reagents for each system, and show that supported catalysis on beads and monolith gives higher yields than for homogeneous catalysis. The synthesis of 2-methylthiomethylpyridines is presented, together with crystal structures of 4-bromo-2-bromomethylpyridine hydrobromide, 4-(4- hydroxyphenyl)-2-methylthiomethylpyridine (L 1 ), PdCl 2 (L 1 ) and PdCl 2 (L 2 ). Hydrogen bonding occurs in 4-bromo-2-bromomethylpyridine hydrobromide as N–H/Br interactions, in 4-(4-hydroxyphenyl)-2- methylthiomethylpyridine as O–H/N to form chains, and in PdCl 2 (L 1 ) as O–H/Cl interactions leading to adjacent p-stacked chains oriented in an antiparallel fashion. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction We have recently examined the ability of palladium(II) com- plexes of neutral 2-organothiomethylpyridine-N,S donor ligands to facilitate Mizoroki–Heck catalysis, in order to explore potential roles for heteroleptic ligands that may exhibit hemilabile activity during the catalytic cycle (Fig. 1). 1 The role of this ligand motif in palladium catalysis has also been explored by Chelucci for addition of diethylzinc to benzaldehyde 2a,b and for allylic substitution, 2a and by Canovese for trimerisation of dimethylacetylene dicarboxylate, 2c and the stoichiometric synthesis of fluoranthenes 2d–f and 2,4-di- ene-6-ynes. 2f We have recently commenced the development of flow-through capillary 3 and chip 3b based microreactors (100– 250 mm internal diameter) employing continuous macroporous organic monolith as support for palladium-catalysed Suzuki– Miyaura 3 and Sonogashira 3c reactions. This flow-through N A B SR R a b c Figure 1. (A) 2-Organothiomethylpyridine ligands (R¼Me, Ph). (B) Polymeric supports (i) Merrifield resin [R¼Cl, typically 2–3% divinylbenzene (DVB) crosslinker]; (ii) Wang resin [R¼p-BrCH 2 C 6 H 4 O, typically 1% DVB]; and (iii) poly(chloromethylstyrene-co-di- vinylbenzene) monolith (CMS/DVB, R¼Cl, typically CMS/DVB ratio w3:2 and (CMS/ DVB)/(porogen) ratio w2:3 in preparations to give highly porous continuous polymeric monolith). * Corresponding authors. Tel.: þ61 3 6226 2162; fax: þ61 3 6226 2858. E-mail addresses: rcj@utas.edu.au (R.C. Jones), allan.canty@utas.edu.au (A.J. Canty). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2009.07.013 Tetrahedron 65 (2009) 7474–7481 Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet