Synthesis Of Oxindole With Quaternary Carbon Center By N-Heterocyclic Carbene Catalysis Or Thermolysis

3,3-disubstituted oxindoles are a class of heterocycles with potential biological activities,which are ubiquitous in many natural products and drugs.As a result,construction of C-3 substituted oxindole skeleton has attracted much attention.However,access to C-3 disubstituted oxindoles has been a great challenge since the construction of quaternary carbon center usually encounters the problem of steric hindrance.In recent years,researchers have made great progresses in the construction of oxindoles with quaternary carbon centers using N-arylacrylamides as starting materials.However,most of these reactions require the employments of transition metals,photocatalysis or stoichiometric oxidants.Considering that the addition of a transition metal,photocatalyst and oxidant might cause series of problems,such as high cost,high toxicity and environmental unfriendliness,it is extremely urgent to develop various green and efficient methods to build 3,3-disubstituted oxindoles from simple and easily-accessed materials.Based on this,the main contents of this paper are as follows:First,we developed a synthetic route to 3,3-disubstituted oxindole via nitrogen heterocyclic carbene catalysis from simple and readily available N-arylacrylamides andα-bromo esters,employing Cs₂CO₃ as base.In addition,we have also developed a synthetic method for 3,3-disubstituted oxindole stemming from cyanoalkylation in the absence of any external additives.Ring-opening reaction of cyclobutanone oxime ester can be realized by simple heating,along with subsequentialγ-cyanoalkyl radical generation,which then smoothly reacts with N-aryl acrylamide to afford oxindoles derivatives with quaternary carbon centers.In conclusion,we mainly studied the construction of 3,3-disubstituted oxindoles with quaternary carbon centers by redox-neutral radical reaction in the absence of any metals,oxidants and photocatalysts.These green protocols feature high efficiency,broad substrate scope,good functional group tolerance,simple procedures and could be amplified to a gram scale.They provide new viewpoints for the synthesis of3,3-disubstituted oxindoles and might have potentially wide application prospects.