Unlocking enhanced reactivity of hexafluoroisopropanol: a sustainable atom economical approach to selective cascade di-π-functionalization of allenamides†

Abstract

Hexafluoroisopropanol (HFIP) mediated di-π-activation of allenamides allows metal-free regioselective intermolecular interception of 4-hydroxycoumarin, establishing a general cascade C–C and C–O bond formation process for accessing novel pyranocoumarins. This method exhibits broad substrate scope, and the feasibility of late-stage functionalization underscores the practicality of this approach. Most significantly, this method is made more resilient and sustainable by a novel precipitation technique that eliminates the use of column chromatography for product isolation. This protocol would be an appropriate means to reach this fascinating chemical space, yet it remains limited to the regioselective 1,2- and 2,3-functionalization, arising from the difficulty associated with the selective functionalization of allenamides and the in situ generated enamide π-bond. The underlying mechanism was unveiled by a combination of control experiments, isotopic labelling experiments and computational investigations, which showcased the critical role of HFIP as a superior mediator for proton-transfer events as well as the pivotal role of the hydrogen bonding interaction with the substrates and intermediates.