Terpenylations using (R)-(–)-α-phellandrene. Synthesis of the (3S,4R)-8,9-dihydro-o- and -p-cannabidiols, their iso-THC's, and the natural dihydrochalcone (3S,4R)-(+)-linderatin

Abstract

Catalysed by toluene-p-sulphonic acid at 5 °C,(R)-(–)-α-phellandrene reacts with olivetol to give (3S,4R)-8,9-dihydro-p- and -o-cannabidiols. At 80 °C under the acid conditions the latter retrogresses substantially to the former and both cyclise giving 51% of (1S,3S,4R)-8,9-dihydro-p-iso-tetrahydrocannabinol and only 3% of the corresponding o-isomer. ¹H N.m.r. and ¹³C N.m.r. data show that (3S,4R)-8,9-dihydro-p-cannabidiol (but not o-) is undergoing restricted rotation near room temperature. By terpenylation of a suitably substituted dihydrochalcone using (R)-(–)-α-phellandrene the natural meroterpene linderatin was synthesized in 46% yield and shown to be the (3S,4R)-(+)-stereoisomer.