Hexafluoroisopropanol (HFIP) has recently become a very popular solvent with uses in many different applications; analysis shows that it possesses a wide range of interesting and unique properties. In this Perspective we detail the main uses of HFIP in the natural sciences and disclose the underlying principles that give it such wide appeal. Accordingly, we will show the broad usage and beneficial effects of HFIP in different fields such as organic, inorganic or physical chemistry, chemical biology and polymer science.

Hexafluoroisopropan-2-ol (HFIP) has been found to be an unusually beneficial solvent for undertaking hypervalent iodine-initiated [2+2] cycloaddition of styrenes. For the initiator phenyliodine(III) diacetate (PIDA), voltammetric data demonstrate that the enhanced reactivity in HFIP is due to its greater oxidizing abilities in this fluorinated solvent such that in HFIP the reactivity of PIDA is comparable if not superior to its fluorinated analog phenyliodine(III) bis(trifluoroacetate). These results contrast with the often reported view that the role of the fluoroalcohol is to stabilize a radical cation formed by single electron transfer. Moreover, combined NMR and HRMS results reveal the formation of a strong H-bonded adduct between the solvent and oxidizing reagent which is the physical origin of the observed altered synthetic reactivity.

The continuous consumption of chemical energy powers biological systems so that they can operate functional supramolecular structures. A goal of modern science is to understand how simple chemical mixtures may transition from non-living components to truly emergent systems and the production of new lifelike materials and machines. In this work a replicator can be maintained out-of-equilibrium by the continuous consumption of chemical energy. The system is driven by the autocatalytic formation of a metastable surfactant whose breakdown products are converted back into building blocks by a chemical fuel. The consumption of fuel allows the high-energy replicators to persist at a steady state, much like a simple metabolic cycle. Thermodynamically-driven reactions effect a unidirectional substrate flux as the system tries to regain equilibrium. The metastable replicator persists at a higher concentration than achieved even transiently in a closed system, and its concentration is responsive to the rate of fuel supply.

Complementary cyclisation reactions of hex-2-ene-1,6-diamine derivatives were exploited in the synthesis of alternative molecular scaffolds. The value of the synthetic approach was analysed using LLAMA, an open-access computational tool for assessing the lead-likeness and novelty of molecular scaffolds.

Developing physical models of complex dynamic systems showing emergent behaviour is key to informing on persistence and replication in biology, how living matter emerges from chemistry, and how to design systems with new properties. Herein we report a fully synthetic small molecule system in which a surfactant replicator is formed from two phase-separated reactants using an alkene metathesis catalyst. The replicator self-assembles into aggregates, which catalyse their own formation, and is thermodynamically unstable. Rather than replicating until the reactants are fully consumed, the metastable replicator is depleted in a second metathesis reaction, and closed system equilibrium is eventually reached. Mechanistic experiments suggest phase separation is responsible for both replicator formation and destruction.