Asymmetric Synthesis of Fluorinated Allenes by Rhodium‐Catalyzed Enantioselective Alkylation/Defluorination of Propargyl Difluorides with Alkylzincs

• Published in: Angewandte Chemie International Edition 2021-09, Vol.60 (38), p.20771-20775
• Main Authors: Ng, Jia Sheng, Hayashi, Tamio
• Format: Article
• Language: English
• Subjects: Alkylation; asymmetric defluorination; Asymmetric synthesis; axially chiral allenes; Chemical bonds; Chemical synthesis; chiral diene ligands; Defluorination; Difluorides; Enantiomers; enantioselectivity; Fluorides; Fluorination; Rhodium
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202109290

The reaction of propargyl difluorides R1CF2C≡CR2 with alkylzincs R3ZnCl giving axially chiral fluorinated allenes R1FC=C=CR2R3 with high enantioselectivity (up to 99 % ee) was found to be catalyzed by a chiral diene/rhodium complex. A key step in the catalytic cycle is selective elimination of one of the enantiotopic fluorides at the β‐position of an alkenyl‐Rh intermediate, which is generated by regioselective addition of R3‐Rh onto the triple bond of the starting difluorides. The reaction of propargyl difluorides, R1CF2C≡CR2, with alkylzincs, R3ZnCl, giving axially chiral fluorinated allenes, R1FC=C=CR2R3, with high enantioselectivity (up to 99 % ee) was found to be catalyzed by a chiral diene/rhodium complex. A key step in the catalytic cycle is selective elimination of one of the enantiotopic fluorides at the β‐position of an alkenyl‐Rh intermediate, which is generated by regioselective addition of R3‐Rh onto the triple bond of the starting difluorides.