Lewis acid-catalyzed cyclisations of homogeranyl carbamates

Geraniol, a member of the terpenoid family known for its various pleasant aromas, has widespread applications in the cosmetic and perfume industry. Many terpenoid derivatives derived from geraniol are known in the literature. In our study, various alkyl and aryl homogeranyl carbamates derived from geraniol and their sequential cyclizations through iodine-mediated reactions were presented. To synthesize homogeranyl carbamates, first, homogeranylamine was obtained through a series of reactions, including radical bromination, nucleophilic displacement, and reduction. Subsequently, obtained homogeranylamine was transformed into homogeranyl carbamates through a nucleophilic addition-elimination. Then, on these homogeranyl carbamate derivatives, iodine-catalyzed electrophilic sequential cyclizations, also known as green chemistry, were performed as described in the literature. Out of the resulting iodotrimethyl octahydroindole carbamates, five compounds were selected and converted into trimethyl octahydroindole carbamates through palladium or tributyltin hydride-catalyzed reduction reactions. The structures of all target compounds were confirmed using various spectroscopic methods such as IR, proton and carbon-13 NMR, and HRMS. The olfactory properties of 33 products were determined by expert evaluators (perfumers), and their in vitro cytotoxicity tests were performed and completed.