SYNTHESIS OF 6-METHOXY-2-METHYL-2-[(1'-METHYL-2',5'-DIOXOCYCLOPENTYL)METHYL]-3,4-DIHYDRO-NAPHTHALEN-1(2H)-ONE - ITS NOVEL BASE-CATALYZED REARRANGEMENT TO A HYDROPHENANTHRENE KETO ACID
Collins, DJ; Fallon, GD; Skene, CE
Reaction of 2-dimethylaminomethyl-6-methoxy-3,4 dihydronaphthalen-1(2H)-one (7) with 2-methylcyclopentane-1,3-dione gave 64% of 6-methoxy-2 [(1'-methyl-2',5'-dioxocyclopentyl) methyl]-3,4-dihydronaphthalen-1(2H)-one(6a), which with 1
equiv. of ethylene glycol in refluxing benzene in the presence of 4-toluenesulfonic acid yielded
a diastereomeric mixture of the. 2',2'-ethylenedioxy derivatives (13a,b); the major
diastereomer (13a) was shown to have 1'SR,2RS stereochemistry by X-ray crystallography. With an
excess of ethylene glycol and prolonged reflux the triketone (6a) underwent aldol
cyclization/acetalization to give 9,9,12,12-bis(ethylenedioxy)-3-methoxy-8-methyl-5,6,8,9,10,11-
hexahydro-8,11-methano-7H-cyclohepta[a]naphthalene (19). With pyridinium 4-toluenesulfonate as
catalyst, aldol cyclization was avoided, and the triketone (6a) afforded 2-[(2',2',5',5'-bis
(ethylenedioxy)-1'-methylcyclopentyl)methyl]-6-methoxy-3,4-dihydronaphthalen-1(2H)-one (15). The
triketone (6a) and its monoacetal (13a,b) were susceptible to reverse Michael cleavage in
reactions with nucleophiles under either acidic or basic conditions. Methylation of the keto
diacetal (15), followed by acid hydrolysis, gave 6-methoxy-2-methyl-2-[(1'-methyl-2',5'-
dioxocyclopentyl)methyl]-3,4-dihydronaphthalen-1(2H)-one (6b); 2-[(2',2'-ethylenedioxy-
1'methyl-5'-oxocyclopentyl)methyl]-6-methoxy-2-methyl-3,4-dihydronaphthalen-1(2H)-one (32),
resulting from incomplete hydrolysis, was shown to have 1'RS,2RS stereochemistry by X-ray
crystallography. The triketone (6b) underwent a novel base-catalysed rearrangement reaction to
give 7-methoxy-2xi,10a-dimethyl-3-oxo-1,2,3,9,10,10a-hexahydrophenanthrene-4-acetic acid (33)
which readily afforded the corresponding enol lactone (35).