Deuteriodifluoromethylation and gem‐Difluoroalkenylation of Aldehydes Using ClCF2H in Continuous Flow

• Main Authors: Fu, Wai Chung (Author), Jamison, Timothy F (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Chemistry (Contributor)
• Format: Article
• Language: English
• Published: Wiley, 2020-11-25T23:00:02Z.
• Subjects: Article
• Online Access: Get fulltext

The deuteriodifluoromethyl group (CF₂D) represents a challenging functional group due to difficult deuterium incorporation and unavailability of precursor reagents. Herein, we report the use of chlorodifluoromethane (ClCF₂H) gas in the continuous flow deuteriodifluoromethylation and gem-difluoroalkenylation of aldehydes. Mechanistic studies revealed that the difluorinated oxaphosphetane (OPA) intermediate can proceed via alkaline hydrolysis in the presence of D₂O to provide α-deuteriodifluoromethylated benzyl alcohols or undergo a retro [2+2] cycloaddition under thermal conditions to provide the gem-difluoroalkenylated product.
Defense Advanced Research Project Agency (DARPA) (Contract ARO W911NF-16-2-0023)