Carbon-Carbon Bond Formation via Palladium-Catalyzed Reductive Coupling of Aryl Halides in Air and Water Sripathy Venkatraman, Taisheng Huang, Chao-Jun Li* Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, USA Fax:(  1)-504-8655596, e-mail: cjli@tulane.edu Received: November 1, 2001; Accepted: February 24, 2002 Abstract: Palladium-catalyzed reactions in general are carried out under an inert atmosphere because the palladium intermediates involved in the catalytic cycles are often known to be sensitive to oxygen. In thispaper,wereportthatvariouspalladium-catalyzed reductive couplings proceed smoothly under an air atmosphere and in aqueous medium. Under the air atmosphere reaction conditions, palladium-triphenyl- phosphinecomplexwasfoundtobeinactive.Byusing zinc as the reducing reagent, aryl halides were homo- coupled to give symmetrical biaryls either in aqueous acetone or in water in the presence of a catalytic amountof18-crown-6atroomtemperature.Botharyl iodides and aryl bromides reacted efficiently under the current reaction conditions. The reaction of arylhalosilanes with aryl halides under refluxing conditions in air and water catalyzed by palladium generated unsymmetrical biaryls efficiently in the presence of either KOH or NaF. Such air-stable couplings are also suitable for a Suzuki-type coupling and a Stille-type coupling. Keywords: aryl halides; biaryls; C  C coupling; cross- coupling; crown compounds; palladium Introduction Palladium-catalyzedreductivecouplingsareamongthe most important carbon-carbon bond forming reactions inmodernsyntheticorganicchemistry. [1] Suchreactions include the p-ally1 chemistry (also asymmetric), [2] the Stille coupling, [3] the Heck reaction, [4] the Suzuki reaction, [5] theSonogashiracoupling, [6] andmanyothers. While these reactions have also been successful in aqueous media, [7] they are generally very sensitive towardsairand,often,particularcareneedstobetaken to exclude air from the reaction system. In addition to the requirement of an inert gas atmosphere, these reactions are often carried out in the presence of a phosphinecompound(whichservedasthecoordinating ligandtostabilizethereactivepalladiumintermediate). In the course of our quest for novel methodologies in aqueousmedia, [8] wecameacrossthisunusualcondition wherein the palladium catalyst seemed to be stable in the air. [9] Subsequently, we found that contrary to generalbeliefs,palladium-catalyzedreductivecouplings inairandwaterarequitegeneral.Herein,wereportthe detailed study of using such catalytic reactions to synthesize symmetrical biaryls via Ullmann-type homo-coupling of aryl halides and unsymmetrical biaryls via cross-coupling of arylhalosilanes with aryl halides. Results and Discussion Ullmann-Type Coupling to Generate Symmetrical Biaryls Conventionally, symmetrical biaryls have been synthe- sizedviatheUllmannreaction [10] ofreductivearylhalide coupling, [11] where copper is used in stoichiometric quantities. [12] Generally, the Ullmann coupling is also carried out at a high temperature, typically above 200 8C.Recently,ithasbeenshownthat,inthepresence of copper(I) thiophene-2-carboxylate, these reactions can be carried out under mild conditions. [13] Palladium has also been shown to catalyze aryl halide homo- couplings under elevated reaction temperatures in the presence of a reducing reagent. [14] Ni/C has also been foundbyLipshutztobeaneffectivecatalystforcoupling of aryl halides. [15] As an effort in developing transition metal-catalyzed carbon-carbon bond formation reac- tionsinwater,weexaminedthepotentialofcarryingout such couplings by using palladium-catalyzed couplings inwater,Equation(1). Ar-Ar ArX Pd cat. M/solvent air atmosphere (1) FULL PAPERS Adv. Synth. Catal. 2002, 344,No.3+4 ¹ VCH Verlagsgesellschaft mbH, 69451 Weinheim, Germany, 2002 1615-4150/02/3443+4-399±405 $ 17.50+.50/0 399