Phosphonium coupling tautomerizable heterocycles

Phosphonium coupling of tautomerizable heterocycles and nucleophiles using the OBt-derived reagents (PyBOP, BOP) is more complicated... 

In 2004-2005, the first phosphonium coupling of tautomerizable heterocycles and amines was reported to enable the direct amination reaction. 

In recent years, direct amination of tautomerizable heterocycles with amines via phosphonium coupling has been widely utilized in the synthesis of various heterocychc compounds used for chemical building blocks or medicinal chemistry. The reaction rate of the direct amination is usually dependent upon the electronic and steric nature of the amine nucleophiles. In principle, electron-richer and sterically less-hindered alkyl amines are much more reactive than aryl amines and nitrogen heterocycles (04AP702,05JOC1957). 

In 2004-2005, we reported direct etherification of tautomerizable heterocycles with oxygen nucleophiles via phosphonium coupling to produce biaryl ethers or alkyl aryl ethers. Phenols are moderately strong nucleophiles, therefore the NaOi-Bu-promoted phosphonium coupling condition was found to be better than the Et3N-promoted condition (04AP702,05JOC1957). 

In 2012, Sharma and coworkers reported the direct arylation of tautom-erizable heterocycles with azoles under microwave conditions. This Pd/Cu catalyzed dehydrative phosphonium coupling via C—OH and C—H bond activation elegandy produced the diheteroaryl compounds via direct arylation of the tautomerizable heterocycle with boronic acids using PyBroP in the presence of Pd(OAc)2 and Cul catalysts (120L1854). 

Interestingly, during their studies on the direct arylation via dehydrative phosphonium coupling, the authors also discovered some side products, the homocoupled symmetrical biheterocycles in about 10-15% yields resulted from the tautomerizable heterocycles. This type of symmetrical biheterocycles have important applications in photochemistry... 

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