Scalable Synthesis of the Amber Odorant 9-<i>epi</i>-Ambrox through a Biomimetic Cationic Cyclization/Nucleophilic Bromination Reaction

A novel biomimetic nucleophilic bromocyclization reaction is used in the key step of a new and straightforward synthesis of 9-<i>epi</i>-Ambrox, an organic compound of high interest and value in the context of fragrances. This strategic reaction allows access to 9-<i>epi</i>-Ambrox on a gram scale from a dienyne derivative, easily available from geraniol, following a sequence of seven steps (35% global yield) with just one purification process. Both enantiomers of the molecule were obtained by a challenging enzymatic resolution

Synthesis of Cyclohexanones through a Catalytic Cationic Cyclization of Alkynols or Enynes

A novel procedure for the synthesis of cyclohexanones from alkynol or enyne derivatives through a cationic cyclization has been developed. The key points to obtain the six-membered ring derivatives are the use of starting materials containing a terminal alkyne, the use of tetrafluoroboric acid as a promoter of the cationic cyclization, and the appropriate selection of 1,1,1,3,3,3-hexa­fluoro­propan-2-ol (HFIP) as solvent. This strategy can be extended to the biomimetic cationic cyclization of several terpene-derived polyenynes

Synthesis of Functionalized 1<i>H</i>‑Indenes and Benzofulvenes through Iodocyclization of <i>o</i>‑(Alkynyl)styrenes

A convenient method for the preparation of synthetically useful 3-iodoindene derivatives has been developed. This protocol, based on the 5-endo iodocyclization reaction of <i>o</i>-(alkynyl)­styrenes, represents one of the scarce examples of halocyclizations using olefins as nucleophilic counterparts and allows the synthesis of both 3-iodo-1<i>H</i>-indenes (from β-alkyl-β-alkyl/aryl-<i>o</i>-(alkynyl)­styrenes) and 3-iodobenzofulvenes (from β,β-diaryl-<i>o</i>-(alkynyl)­styrenes) in good yields under mild reaction conditions. In addition, related alkoxyiodocyclization processes are described, which are particularly interesting in their intramolecular version because they allow the synthesis of heteropolycyclic structures containing the indene core. Finally, the usefulness of the prepared 3-iodoindenes has been demonstrated by the synthesis of several polysubstituted indene derivatives through conventional palladium-catalyzed cross-coupling reactions and iodine–lithium exchange processes