Enantioselective Palladium‐Catalyzed [3+2] Cycloaddition of Trimethylenemethane and Fluorinated Ketones

• Published in: Angewandte Chemie Vol. 130; no. 38; pp. 12513 - 12517
• Main Authors: Trost, Barry M., Mata, Guillaume
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 17.09.2018
• Subjects: Aldehydes; Aliphatic compounds; Amides; Asymmetrische Katalyse; Atom economy; Chemical synthesis; Chemistry; Cycloaddition; Cycloadditionen; Dihydrofurane; Enantiomers; Esters; Fluor; Fluorination; Intermediates; Ketones; Palladium
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201807308

A nitrile‐substituted trimethylenemethane (TMM) donor undergoes palladium‐catalyzed [3+2] cycloadditions with fluorinated ketones to generate tetrasubstituted trifluoromethylated centers in high enantioselectivity under mild conditions. The generation of the palladium–TMM complex was achieved by a self‐deprotonation strategy, which shows remarkable improvements in regiocontrol, efficiency, and atom economy of asymmetric [3+2] cycloadditions. Moreover, the versatility of the nitrile group provides direct access to a variety of synthetically useful intermediates, including amides, aldehydes, and esters. The developed reaction conditions allow for the synthesis of a wide variety of aromatic, heteroaromatic, and aliphatic fluorinated dihydrofurans in excellent regio‐ and enantioselectivities. Eine Palladium‐katalysierte enantioselektive [3+2]‐Cycloaddition eines Nitril‐substituierten Trimethylenmethan(TMM)‐Donors wurde entwickelt. Die Generierung des TMM wurde durch die Acidität der C‐H‐Bindung neben der Nitril‐Gruppe ermöglicht. Der Donor reagierte mit verschiedenen fluorierten Ketonen zu 2,2‐disubstituierten Dihydrofuranen in hohen Ausbeuten und Enantioselektivitäten.