Utilization of fluoroform for difluoromethylation in continuous flow: a concise synthesis of α-difluoromethyl-amino acidsElectronic supplementary information (ESI) available: Experimental procedures, further optimization data and characterization of all compounds. See DOI: 10.1039/c7gc02913f

Fluoroform (CHF 3 ) can be considered as an ideal reagent for difluoromethylation reactions. However, due to the low reactivity of fluoroform, only very few applications have been reported so far. Herein we report a continuous flow difluoromethylation protocol on sp 3 carbons employing fluoroform as a reagent. The protocol is applicable for the direct C α -difluoromethylation of protected α-amino acids, and enables a highly atom efficient synthesis of the active pharmaceutical ingredient eflornithine. Difluoromethylated esters, malonates and amino acids (including the drug eflornithine) are obtained by a gas-liquid continuous flow protocol employing the abundant waste product fluoroform as an atom-efficient reagent.