Efficient syntheses of α-cedrene (1), α-pipitzol (2), and sec-cedrenol (3) were carried out using a new method, which was inspired by the proposed biosynthesis of the tricyclic skeleton of cedrol (12). The key transformation begins with the oxidative dearomatization of curcuphenol (5a) followed by an intramolecular [5 + 2] cycloaddition of the respective phenoxonium intermediate across the tethered olefin. The benzylic stereocenter effectively guides the formation of the first two stereocenters during the [5 + 2] reaction. The cascade then terminates with the selective incorporation of acetic acid to generate a third stereocenter, setting it apart from other previous cationic [5 + 2] reactions. The phenolic precursors (5a-h) are constructed from readily available salicylaldehydes, either as the racemate (one pot) or as a specific enantiomer (four pots) by a modification to our method for the generation of ortho-quinone methides (o-QMs).

Stereodivergent total syntheses of ent-heliespirone A and C were both completed in 11 vessels and ∼24% combined overall yield (A + C). These syntheses employed an identical inverse demand Diels-Alder reaction between a surrogate for an extendedly conjugated γ-δ unsaturated ortho-quinone methide and L-lactic-acid-derived exocyclic enol ether. Novel reactions of special note include a diastereoselective reduction of a chroman spiroketal by combination of borontrifluoride etherate and triethyl silane, along with oxidative rupture of a chroman etherial ring into the corresponding p-quinone by argentic oxide (AgO). In addition, an unusual intramolecular etherification of a 3° alcohol caused by cerium ammonium nitrate was observed.

Total syntheses of two structures purported as (+)-heliananes were completed in six pots. Spectral comparisons, between the synthetic and natural compounds, revealed a misassignment of the eight-membered ring in the heliananes. The key step in the syntheses of the proposed structures and the confirmation of their actual structures was a diastereoselective inverse-demand Diels-Alder reaction between an optically active enol ether and an ortho-quinone methide species, which was generated in situ at low temperature by the sequential addition of methylmagnesium bromide and di-tert-butyl dicarbonate to a salicylaldehyde.

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An acid-catalyzed intramolecular [4 + 2] cycloaddition of a non-natural bisabolene is reported. The key cyclocondensation was developed to access cyclic sesquiterpenes from linear phenolic precursors by generating a reactive o-quinone methide intermediate to initiate a cascade reaction. The new method was applied to the first total synthesis of (±)-heliol.