Aqueous conditions phosphine-free method

D.iii.b. Aqueous Phosphine-Free Method. The use of palladium catalysts without the addition of phosphine ligands for cross-coupling with organoboron compounds in aqueous media allows a dramatic increase in catalyst efficiency, with the reaction being performed under milder conditions. 

Besides iodo- and bromoderivatives, the Heck reaction has been applied to diazonium and iodonium salts, always in phosphine-free processes. The former are usually processed in alcoholic solutions, sometimes in the presence of water.f The reactions of aryl and alkenyliodonium salts are done under very mild conditions in aqueous solvents,t i t ° which allows one to use this method for selective arylation (alkenyladon) of allylic alcohols (Scheme 34). 

It should be noted that cross-coupling in the presence of phosphine complexes of palladium usually requires high amounts of catalyst, with initial loadings of 25-30 mol% not being uncommon. An entirely new approach to the Suzuki reaction is phosphine-free palladium catalysis. The use of palladium catalysts without the addition of phosphine ligands for cross-coupling with organoboron compounds in aqueous media opened a new chapter in the story of this powerful synthetic method. This approach allows catalyst efficiency to be dramatically increased, and the reaction to be performed under milder conditions. 

There is only a single example of application of this method to the synthesis of biologically interesting compounds. Stockland et al. carried out rhodium-catalyzed hydrophosphinylation of ethynyl steroids of type 185, as shown in Scheme 47.46, to obtain terminal phosphinates or phosphine oxide derivatives 186.As mentioned earlier, the reaction afforded -products exclusively. The authors examined different reaction conditions, with a focus on the green approach hence, solvent-free and aqueous conditions were used in combination with microwave heating. 

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