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.

A short (10 step) and efficient (15% overall yield) synthesis of the natural product (-)-(3 R)-inthomycin C is reported. The key steps comprise three C-C bond-forming reactions: (i) a vinylogous Mukaiyama aldol, (ii) an olefin cross-metathesis reaction, and (iii) an asymmetric Mukaiyama-Kiyooka aldol. This route is notable for its brevity and has the advantage of lacking stoichiometric tin-promoted cross-coupling reactions present in previous approaches. Initial investigations on the biological activity of (-)-(3 R)-inthomycin C and structural analogues on human cancer cell lines are also described for the first time.

Pd(II)-catalysed ortho-arylation of benzylic heterocycles with arylboronic acid pinacol esters (Ar-BPin) via directed C-H bond activation to generate the desired biaryl products is reported. This methodology is efficient and applicable to a wide range of functionalised Ar-BPin and benzylic heterocycles, allowing the direct synthesis of important biaryl motifs in modest to good yield.

Key enolate alkynylation and ring closing Heck reactions have been used to make the core of the taiwanschirin natural products.