Study On The Cyanomethylation Reaction Catalyzed By N-Heterocyclic Carbenes

β-Hydroxynitriles are useful building blocks for the synthesis of β-hydroxycarboxylic acids and theirderivatives, γ-amino alcohols, so attract great interesting of organic chemists. The cyanomethylationreaction is the most general, straightforward and widely applied method for synthesis of β-Hydroxynitrilesand their derivatives. The NHCs as an important organocatalyst, it attract more and more attention of theorganic workers due to the efficiency catalytic activity,environment-friendly and easy to prepare, soN-heterocyclic carbenes (NHCs) were obtained quickly development as a very important type oforganocatalysts in the past two decades. In this paper, NHCs catalyzed cyanomethylation reaction ofaldehydes with TMSAN was mainly studied, including two parts as follows：1．One stable NHC and five different types of precursor for NHC were synthesized firstly. Using theseNHCs as catalysts, TMSAN as nucleophile respectively, cyanomethylation reaction of aldehyde wassuccessfully achieved. The optimal reaction conditions was established (DMF,5mol%IPr) the generalityof the cyanomethylation was evaluated, obtain16β-Hydroxynitriles in61～84%yield. Finally, possiblereaction pathes about silicon-closely activation were proposed.2．Using these NHCs as catalysts, the cyanomethylation reaction of ketone with TMSAN was attempted,found Ketones and silicon reagents generated silyl enol ethers substance. It is worthwhile noting that theaddition of2,2,2-trifluoroacetophenone and TMSAN proceeds smoothly to give in89%yield, whichcontains a quaternary carbon center. The same time, the cyanomethylation reaction of different types imineswith TMSAN was attempted, but not obtain the target product. When attempted Ts-imines with TMSAN,however, imines with carbene forming intermediates.In summary, we have demonstrated a NHC-promoted cyanomethylation reaction of TMSAN withvarious aldehydes. The mild conditions, simple procedure provides a valuable approach for the preparationof β-Hydroxynitriles. This method has many advantages such as simple procedure, inexpensive materials,high yield, environmental friendly and so on.