In this paper we will disclose a chemistry story that started
with a single molecule, the monoterpene grandisol, used in
protecting cotton crops from an important pest, Anthonomus
grandis Boheman. Initially, efforts were aimed at giving ever
more practicality, versatility, and efficiency to a synthetic
scheme that was centered on the key role of the 2,5-dimethylbicyclo[3.2.0]heptan-endo-2-ol, available from intermolecular photocyclization and methylation or, better and more
conveniently, by an intramolecular copper(I)-catalyzed photobicyclization of the 3,6-dimethylhepta-1,6-dien-3-ol. We have
developed an enantiospecific synthesis of both enantiomers of
grandisol although some drawbacks would preclude scale up
and commercialisation. The major limits of this original single-target synthetic scheme are pointed out along with the changed
landscape resulting from recent developments in the fields of
bioorganic chemistry and entomology. These changes prompted
the elaboration of a new strategy focused on the conception
and the development of a practical and efficient preparation
bicyclo[3.2.0]hept-2-en-6-ones. The “bicyclo[3.2.0]hept-2-en-6-one approach” stems from a very convenient and general
preparation, without photochemical steps, of bicyclo[3.2.0]hept-2-en-6-ones. These compounds proved to be amenable to
selective manipulations to prepare not only grandisol but also
other important molecules such as lineatin, filifolone, and
raikovenal in multitarget and versatile synthetic schemes.
Moreover, through resolution of the bicyclo[3.2.0]hept-2-en-6-ones, the procedures can be used to produce enantiomerically
pure products. The bismethylation of the carbon atom adiacent
to the carbonyl group as well as the conversion into the
corresponding unsaturated bicyclic lactones are two important
reactions that amplify the potential utility of bicyclo[3.2.0]hept-2-en-6-ones. Their peculiar reactivity, ascribed to the fact that
the carbonyl group and the carbon−carbon double bond are
attached to the same bridge-head carbon atom, has been
demonstrated by the high chemio-, regio-, and stereoselectivity
of the NBS-induced lactonization.