Palladium phosphonium salts

Phosphonium salts can be synthesized by the transition-metal-catalyzed addition reaction of triaryphosphines and acids to unsaturated compounds. The reaction of PPh3, CH3SO3H, and alkynes in the presence of a palladium or rhodium catalyst gave alkenylphosphonium salts. Although Pd(PPh3)4 directed the C-P bond formation at the internal carbon atom of aliphatic 1-alkynes (Markovnikov mode), [RhCl(cod)]2... 

Allylphosphonium salts are synthesized by substitution of allyl halides with PPh3. The use of allyl alcohol, allyl acetate, or nitropropene with a palladium catalyst has also been reported.19 It is shown in this study that the organophosphorous compounds can be obtained by a palladium-catalyzed addition to an allene. A notable aspect of this method is that it can control the stereochemistry of the phosphonium salt, and that (Z)-allylphosphonium salts have been obtained in pure form for the first time. 

More recently a variation of this mechanism was reported by Novak [37], The mechanism involves nucleophilic attack at co-ordinated phosphines and it explains the exchange of aryl groups at the phosphine centres with the intermediacy of metal aryl moieties. After the nucleophilic attack the phosphine may dissociate from the metal as a phosphonium salt. To obtain a catalytic cycle the phosphonium salt adds oxidatively to the zerovalent palladium complex (Figure 2.38). Note where the electrons go . 

Interestingly, various phosphonium salts have been applied [13] as constituents of palladium catalysts for hydrodimerization of butadiene and isoprene about the same time when the results of Kuraray were disclosed. These were obtained by quatemization of aminoalkylphosphines with methyl iodide or HQ (Ph2P-R-NH2 type compounds are known to yield phosphonium salts with these reagents). Although the catalysts prepared in situ from [PdCU] were reasonably active (TOF-s of 10-20 h ) the reactions always yielded complex product mixtures with insufficient selectivity towards the desired 1,7-octadienyl derivatives. 

In a 1985 patent by Hoffmann-La Roche, the Wittig condensation was also the crucial step in assembling isotretinoin (1, Scheme 2). Under the optimized conditions, 1.03 equivalents of phosphonium salt 8 was condensed with 1 equivalent of hydroxybutenolide 9 in the presence of 1.25 equivalents of 2 N KOH in isopropanol at -30°C for 1 to 1.5 h. The product (91.5% total yield) consisted of 75.9% of 2-cis-4-cis-vitamin A acid (10) and 16.7% of isotretinoin (1). Without separation, the mixture of 10 and 1 was subjected to palladium-catalyzed isomerization conditions the mixture was heated at 50°C for 1 h in acetonitrile in the presence of 0.10 mol% of palladium(n) nitrate, four equivalents (based on palladium nitrate) of triphenylphosphine and 2... 

The process reported here uses a clever combination of the factors that promote catalyst life and efficiency. The soluble phosphine or its phosphonium salt, used in a molar excess of about 50 over palladium, stabilizes the palladium complex in aqueous solution the sulfolane-water solution ensures the solubility of the reactants, while extraction with hexane under CO2 pressure recovers the product with only small contamination by palladium, phosphorus or nitrogen. The phosphine or its phosphonium salt and the ammonium bicarbonate remain in the aqueous solution. Since the TON is good and the solution can be recycled, consumption of palladium is very low. 

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