Chirality retention in Friedel–Crafts spiroannulation for iterative synthesis of spiro-bridged conjugated carbocycles

Abstract

The formation of chiral organic molecules from Friedel–Crafts reactions of chiral alcohols has been deemed impractical due to racemization via carbocation formation. Here we demonstrate the preservation of stereochemistry in intramolecular Friedel–Crafts alkylation reactions, expanding the boundaries of accessible chiral chemistry. Mechanistic investigations show that the retention of stereochemistry stems from the chirality memory of transient, axially chiral carbocation intermediates. This finding allows the synthesis of axially chiral spirocarbon-bridged conjugated carbocycles. Leveraging a rhodium-catalysed regioselective C–H activation–annulation approach, the reaction of thiobenzamide with phenylethynyl tertiary alcohol is a crucial step in expanding the spiro-bridged skeleton. We used this approach to develop an iterative synthetic sequence to construct enantiopure spirocarbon-bridged pure-hydrocarbon oligo(trans-stilbene) compounds. Notably, in the concluding step of the iterative synthesis, all chiral tertiary alcohol units undergo a stereospecific one-shot conversion to form multiple spirocyclic structures, resembling a ‘zipping up’ process. This synthetic strategy facilitates both the longitudinal and lateral extension of spiro-bridged conjugated structures, with promising applications in circularly polarized lasers. A strategy that preserves stereochemistry in intramolecular Friedel–Crafts alkylation is reported. An iterative synthetic approach to extend spiro-bridged molecular skeletons via C–H activation–annulation is developed, where the stereoretentive one-shot conversion to form multiple spirocarbon-bridged carbocycles resembles a ‘zipping up’ process.