Cycloisomerization of Carbamoyl Chlorides in Hexafluoroisopropanol: Stereoselective Synthesis of Chlorinated Methylene Oxindoles and Quinolinones
José F. Rodríguez, Anji Zhang, Jonathan Bajohr, Andrew Whyte, Bijan Mirabi, Mark Lautens
Abstract
Hexafluoroisopropanol (HFIP) was employed as an additive for the generation of 3-(chloromethylene)oxindoles via the chloroacylation of alkyne-tethered carbamoyl chlorides. This reaction avoids the use of a metal catalyst and accesses products in high yields and stereoselectivities. Additionally, this reaction is scalable and proved amenable to a series of product derivatizations, including the synthesis of nintedanib. The reactivity of alkene-tethered carbamoyl chlorides with hexafluoroisopropanol (HFIP) was harnessed towards the synthesis of 2-quinolinones.
Topics & Concepts
ChemistryCycloisomerizationAlkyneMethyleneStereoselectivityReactivity (psychology)Combinatorial chemistryCatalysisAlkeneOrganic chemistryAlternative medicineMedicinePathologyCatalytic C–H Functionalization MethodsFluorine in Organic ChemistrySynthesis and Biological Evaluation