Alkali-Metal Base Catalyzed Electrocyclization of Isoprene Derivatives

The catalytic electrocyclization of heptatrienes represents an attractive strategy to access seven-membered carbocycles from acyclic precursors, whose medium-size cyclic saturated hydrocarbon counterparts display physicochemical properties of interest for jet-fuel applications. Here we uncover the potential of alkali-metal amides to enable an efficient, high-yielding and multigram-scale electrocyclization of biobased ocimene and related trienes derived from isoprene. Experimental results show that both the nature of alkali metal (Li vs Na) and coordination by PMDETA (N,N,N',N″,N″-pentamethyldiethylenetriamine) play a decisive role in enabling efficient turnovers. Trapping and structural authentication of key metalated intermediates, together with DFT calculations, provide valuable mechanistic insights into the cyclization pathway and the factors governing reactivity. The transformation can proceed catalytically at relatively low loadings in neat conditions, with lithium-based catalysis providing selectively 1,1,4-trimethylcycloheptadienes albeit at higher catalyst loadings of 10 mol%, whereas sodium-based systems can operate at lower loadings of 2 mol% and can promote the isomerization/cyclization of other trienes.