Quinoline-derived Oxime Assisted Direct ?-C(sp~3)-H Nitrooxylation Of Alcohols

In recent years,Pd(?)-catalyzed C-H activation functionalization has made remarkable progress.Inert C-H bonds in many substrates have been effectively activated,and carbon-heteroatom chemical bonds have been successfully constructed.At the same time,the development of directing group strategies has made the regioselectivity and stereoselectivity of the reaction well controlled.Nitrate ester compounds have important application value in the fields of medicinal chemistry and energetic materials.However,the work of directly converting the inactivated C(sp³)-H bond to the nitrate ester structure is rarely reported.In this paper,we studied the transition metal-catalyzed direct nitrooxylation functionalization of alcohol substrates,which are widely present in organic molecules.The main content is divided into the following aspects:Using pyridyl benzyl ethers-masked alcohol molecule or oxime-masked alcohol molecule as substrates,a variety of experimental conditions were tried to explore the reaction conditions of the non-activated?-and?-position of the alcohol.Finally,when using palladium acetate as the catalyst,silver nitrite as the nitrate source,selective fluorine reagent as the oxidant,tetrabutylammonium bisulfate as the phase transfer catalyst,and1,2-dichloroethane as the solvent,After heating to 80?in the air atmosphere and reacting for18 h,the template substrate can generate?-nitric acid esterified product with 68%yield.Subsequently,this paper successfully completed many substrate expansion experiments under the optimal reaction conditions.This method strategy can be well compatible with various types of alcohol substrates,and finally 23?-position nitrooxylation products of oxime-masked alcohols can be obtained in a moderate to excellent yield,and the data were characterized by ¹H NMR,¹³C NMR,and HRMS.Finally,this paper also designed the subsequent derivatization reaction,realized the conversion of the nitrate ester structure to the azide group.At the same time,the directing group was successfully removed by a simple method,and the?-position nitrated alcohol compound was synthesized.Finally,through free radical capture experiment,H/D exchange experiment,cyclopalladium intermediate capture experiment and other mechanism experiments,combined with the success of previous studies,it is speculated that the free radical reaction mechanism and Pd(?)/Pd(?)of the catalytic cycle.