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

Abstract

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′,2̶-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 tri-ketone (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-dihydronaphtha - len-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-2ξ,10a-dimethyl-3-oxo-1,2,3,9,10,10a-hexahydrophenanthrene-4-acetic acid (33) which readily afforded the corresponding enol lactone (35).

Highly Regioselective Construction of Spirocycles via Phosphine-Catalyzed [3 + 2]-Cycloaddition

“…6-Methoxy-2-methylene-3,4-dihydro-2 H -naphthalen-1-one (1b): white solid; mp 44−45.5 °C (ethyl acetate−petroleum ether); IR (KBr) ν 1664, 1597 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 7.99 (d, J = 8.7 Hz, 1 H), 6.76 (dd, J = 8.7, 2.4 Hz, 1H), 6.61 (d, J = 2.1 Hz, 1H), 6.10 (br s, 1H), 5.31 (br s, 1H), 3.76 (s, 3H), 2.87 (t, J = 5.9 Hz, 2H), 2.74 (m, 2H); MS ( m / z ) 188 (M + , 100), 160, 148, 145, 120, 115, 91. Anal.…”

Synthesis of 7a-Substituted Hajos−Wiechert Ketone Analogues

“…During these cyclizations the formation of diketone 3 was often observed, which accounts for the modest yields in some reactions. This retro-Michael reaction has been previously reported in the study of intramolecular cyclizations of a triketone similar to 2 …”

“…This retro-Michael reaction has been previously reported in the study of intramolecular cyclizations of a triketone similar to 2. 22 These optimized conditions were then applied to the preparation of HW-ketone analogues (Figure 4). All of these compounds were prepared in good yield (except for the sterically demanding 1g) and moderate to excellent enantiopurity as determined by chiral HPLC.…”