Sequential Acylation/Silylation/Hetero-Claisen Rearrangement of Nitroalkanes for the Synthesis of Protected Hydroxyoxime Derivatives

Sequential acylation-silylation of nitroalkanes leads to O-silylated alpha-acyloxyoximes in high yields. The first step of the reaction involves deprotonation of nitro compound with sodium hydride promoted by DBU or alcohol/15-crown-5 system followed by treatment with acyl chloride. In situ generated acyl nitronate is further silylated by silyl triflate that triggers hetero-Claisen [3,3]-rearrangement within N-acyloxyenamine moiety furnishing orthogonally protected oxime derivatives. The procedure has large substrate scope for both nitroalkanes and acylating agents (acyl chlorides, chloroformates) and allows tuning of reaction conditions depending on the particular type of substrate. Application of obtained oxime derivatives in organic synthesis is demonstrated.

Automated summary

Sequential acylation-silylation of nitroalkanes leads to high yields of O-silylated alpha-acyloxyoximes. The reaction has a broad substrate scope for both nitroalkanes and acylating agents, with the ability to adjust reaction conditions based on the specific substrate. Additionally, the study demonstrates the application of the obtained oxime derivatives in organic synthesis.