TETRAHEDRON LETTERS Tetrahedron Letters 42 (2001) 5373–5376 Pergamon Synthesis of symmetrical triarylphosphines from aryl fluorides and red phosphorus: scope and limitations Terence L. Schull,* Susan L. Brandow and Walter J. Dressick Center for Bio /Molecular Science and Engineering, Code 6950, U.S. Naval Research Laboratory, 4555 Overlook Avenue, SW, Washington, DC 20375 -5348, USA Received 29 May 2001; revised 14 June 2001; accepted 15 June 2001 Abstract—The reaction of aryl fluorides with phosphide anion, generated in situ from the reduction of red phosphorus by lithium metal in liquid ammonia, gave symmetrical triarylphosphines in fair to good yields. Phosphonodiamide, sulfonamide, 2-oxazolyl, and nitrile groups were stable to the reaction conditions, while nitro and bromo substituents were not. para -Substituted aryl fluorides gave higher yields than meta -substituted aryl fluorides, and ortho -substituted aryl fluorides failed to react. © 2001 Published by Elsevier Science Ltd. Functionalized triarylphosphines are widely used as ligands for transition metal complexes 1 and as synthetic intermediates for the preparation of novel materials. 2 The classical method for preparing triarylphosphines involves the reaction of Grignard reagents or aryl- lithium reagents with phosphorus halides. 3 More recent methods include the palladium-catalyzed phosphination of aryl triflates using triarylphosphines, 4 the palladium- catalyzed coupling of aryl halides with trimethylstan- nyl- or trimethylsilyldiphenylphosphines, 5 nucleophilic phosphanylation of aryl fluorides in superbasic media, 6 palladium-catalyzed P-C cross-coupling reactions of primary and secondary phosphines with functionalized aryl iodides, 7 or a combination of nucleophilic phos- phanylation and palladium-catalyzed P-C coupling. 8 Our interest in the symmetrical triarylphosphine P(4- C 6 H 4 PO 3 Na 2 ) 3 , triphenylphosphine triphosphonate (TPPTP), led us to the development of a synthesis of this compound, 9 which combines the nucleophilic aro- matic substitution chemistry of aryl fluorides with the in situ formation of phosphide anion in liquid ammonia using red phosphorus and alkali metals. 10 In this way, the use of the very expensive and toxic phosphine gas was avoided. The surprising result of this preparation was that the triarylphosphine was formed almost exclusively, even when sub-stoichiometric amounts of the aryl fluoride precursor were used. The selectivity of the reaction and convenience of the preparation prompted us to investi- gate whether this methodology was general in scope. In a typical reaction, 9 a suspension of red phosphorus in liquid ammonia is stirred with three equivalents of lithium metal in the presence of one equivalent of tert -butanol, added slowly as a 10% solution in THF. The presence of a proton donor accelerates the reduc- tion of the red phosphorus and is believed to result in an equilibrium mixture of H 2 P - and LiNH 2 . 10 A THF solution of the aryl fluoride is then added dropwise and the reaction is stirred at reflux (-33°C). With reactive substrates, an immediate color change is observed, and the reaction mixture becomes a deep red by the end of the addition. In these cases, the dry ice in the Dewar condenser is not replenished, and the liquid ammonia is allowed to slowly evaporate while stirring the reaction mixture at room temperature overnight. The work-up consists simply of adding water and ether to the residual reaction mixture, filtering if necessary, and separation of the phases. We have found that the reaction is restricted to acti- vated aryl fluorides containing electron-withdrawing groups in the para - or meta -position. In contrast to nucleophilic phosphanylations with PH 3 in DMSO 6a or Ph 2 PK in DME or THF, 11 the reaction failed for ortho -substituted aryl fluorides, presumably because Keywords : aryl fluoride; liquid ammonia; lithium phosphide; red phosphorus; triarylphosphine. * Corresponding author. Tel.: (202) 404-6043; fax: (202) 767-9594; e-mail: tls@cbmse.nrl.navy.mil 0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd. PII:S0040-4039(01)01059-0