High pressure Diels-Alder approach to hydroxy-substituted 6a-cyano-tetrahydro-6H-benzo[c]chromen-6-ones: a route to delta(6)-cis-cannabidiol.
Diels-Alder cycloaddition reactions of 3-cyanocoumarin, hydroxy-substituted 3-cyanocoumarins and mesyl-substituted 3-cyano-coumarins with methyl-1,3-butadienes carried out under high pressure (11 kbar) are reported. Activation by high pressure allows these reactions to proceed satisfactorily under mild conditions to produce 6a-cyano-hydroxy- and 6a-cyano-mesyl-tetrahydro-6H-benzo[c]chromen-6-ones in moderate to excellent yield. The synthesis of cis-1-hydroxy-9-methyl-3-pentyl-6a,7,10,10a-tetrahydro-benzo[c]chromen-6-one as precursor of Delta(6)-3,4-cis-cannabidiol (Delta(6)-cis-CBD) and Delta(8)-cis-tetrahydrocannabinol (Delta(8)-cis-THC) is outlined.
Ballerini
Eleonora
E
Dipartimento di Chimica, Università degli Studi di Perugia, via Elce di Sotto 8, 06123 Perugia, Italy.
Minuti
Lucio
L
Piermatti
Oriana
O
Pizzo
Ferdinando
F
D001578:Benzopyrans / Q000138:chemical synthesis*; D002185:Cannabidiol / Q000138:chemical synthesis*; D003374:Coumarins / Q000737:chemistry; D006900:Hydroxylation; D011312:Pressure
D001578:Benzopyrans; D003374:Coumarins; D002185:Cannabidiol