Cycloisomerization of Carbamoyl Chlorides in Hexafluoroisopropanol: Stereoselective Synthesis of Chlorinated Methylene Oxindoles and Quinolinones. Issue 34 (16th July 2021)

• Record Type: Journal Article
• Authors: Rodríguez, José F.; Zhang, Anji; Bajohr, Jonathan; Whyte, Andrew; Mirabi, Bijan; Lautens, Mark
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 34(2021)
• Page Start: 18478
• Page End: 18483
• Publication Date: 2021-07-16
• Subjects: chloroacylation -- cycloisomerization -- HFIP -- methylene oxindoles -- stereoselectivity; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202103323
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : The application of hexafluoroisopropanol (HFIP) as a reagent in the cycloisomerization of alkyne‐tethered carbamoyl chlorides is demonstrated. The chlorinated methylene oxindole products are obtained in excellent E ‐selectivities. This reactivity was also extended towards the synthesis of chlorinated methylene pyrrolidones and 2‐quinolinones.