Iron-Based Eutectic Mixtures in Organic Synthesis: Recent Progress and Future Directions

Over the past decade, a variety of acidic deep eutectic solvents have emerged as effective and sustainable alternatives to volatile organic compounds (VOCs) in several organic transformations.1 Within this framework, Lewis acidic deep eutectic solvents (LADESs) based on iron salts are particularly attractive, as iron is an earth-abundant, low toxicity transition metal with excellent redox properties.2 In this communication, we present several applications of iron-based DESs, including: a) the Meyer-Schuster rearrangement of propargylic alcohols at room temperature and under aerobic conditions (Figure 1a);3 b) the oxidation of secondary alcohols (Figure 1b);4 and c) the synthesis of amides and arylsulfonamide derivatives (Figure 1c).4 Notably, we recently demonstrated the efficacy of a FeCl₃·6H₂O/glycerol eutectic mixture (3:1 mol/mol) as a highly effective medium for the Ritter reaction of aliphatic and aromatic secondary and tertiary alcohols with both aliphatic and aromatic nitriles. The protocol is operationally simple, scalable, and generally proceeds at 40 °C within 4 h, affording the corresponding amides in yields of up to 98% through straightforward crystallization (Figure 1d). The eutectic mixture can be effectively reused for up to eight consecutive cycles. The robustness and sustainability of the method were further demonstrated through the multigram-scale synthesis of the drug Chlodantane under these conditions