Studies On The Cyanation Reaction Of Bifunctional Cyanating Reagent With Nitroolefin Or Sterone

The cyano group widely exists in natural products and drug molecules,and could serve as a versatile synthetic handle.Therefore,the selective synthesis of nitriles is of great importance.Using bifunctional cyanating reagents Me₂?CH₂Cl?Si CN as the cyanating source,this thesis has achieved two parts of research work:improving the asymmetric cyanation of nitroalkenes in terms of enantioselectivity and substrate scope,and optimizing the synthetic procedure of 17?-cyano-17?-hydroxyandrosta-17-?chloromethyl?dimethylsilyl ether.The specific work is described below.1)A highly enantioselective cyanation of?-alkyl and?-CF₃-?-aryl/alkyl substituted nitroolefins with the cyanating source Me₂?CH₂Cl?Si CN is realized by using chiral?salen?Ti Cl₂/phosphorane complex as the catalyst,affording a series of chiral?-nitronitriles with good to excellent yields and enantioselectivities.Notably,this method could achieve the best enantioselectivity and the broadest substrate scope so far in the asymmetric cyanation of nitroolefins.Control experiments and mechanistic studies have shown that the activation of?salen?Ti Cl₂ complex by phosphorane is important to improve the reactivity and enantioselectivity.In addition,Me₂?CH₂Cl?Si CN proves to be more active than TMSCN in this reaction.The products obtained can be applied for the efficient synthesis of chiral?²-or?^2,2-amino acids and fluorinated nitrogen-containing heterocycles.2)A facile one-step synthesis of steroidal drug intermediate 17?-cyano-17?-hydroxyandrosta-17-?chloromethyl?dimethylsilyl ether from Me₂?CH₂Cl?Si CN is futher optimized by using 4 mol%inexpensive DBU as the catalyst.The reaction can be scaled up to 100 mmol in air at room temperature,affording the target pure product in 72%yield through a simple post-treatment and recrystallization,and a total yield of 85%is achieved if the mother liquor is purified by column chromatography.Compared to the reported two-step synthesis,this method has some following advantages such as improved atomic economy and step economy,mild reaction conditions,simple post-treatment,obviously reduced waste generation and cost in purification.