A Formylation-Cyclization Method of Synthesis of Cycloalkenones from Unsaturated Ketones. 2. Simple Synthesis of Some Functionalized Bicyclononane Derivatives

Article abstract of DOI:10.1021/jo00225a054

The potential generality of formylation-cyclization of a variety of γ,δ-unsaturated methyl ketones as a route to some functionalized bicyclo<3.3.1>nonane derivatives has been examined.Thus, perchloric acid catalyzed reactions of β-diethoxyethyl ketones 2a-c and 14a-c, derived from the 2-acetyl-2-methylhexahydrophenanthrenes and tetrahydrofluorenes 1a-c and 13a-c, respectively, in the absence and presence of triethyl orthoformate, afforded the corresponding bridged dienones 3a-c and 15a-c and enones 4a-c and 16a-c in excellent yields.The bridged enones 4a-c and 16a-c are also formed by direct reaction of the methyl ketones 1b,c and 13a-c with triethyl orthoformate and perchloric acid, similar to that with 1a, reported earlier.While similar perchloric acid catalyzed reaction of 2b and 13a,b with trimethyl orthoformate gives the dienones 3b and 15a,b, the respective p-methoxystyrenoid derivatives 1c and 13c under identical conditions lead to the bicyclo<2.2.2>octanones 22 and 23.Unlike the aforementioned 2-methyl 2-acetyl substrates, the desmethyl ketones 18a,b and 20 and the respective β-diethoxyethyl derivatives 24a,b and 25 on reaction with triethyl orthoformate and perchloric acid give only the respective bridged cyclodienones 26a,b and 27 in good yield.Similarly, perchloric acid catalyzed reactions of β-diethoxyethyl ketones 31a-d derived from 1-acetyl-4-arylcyclohex-3-enes (30a-d) in the presence or absence of triethyl orthoformate lead to the respective 6-arylbicyclo<3.3.1>nona-3,6-dien-2-ones (32a-d).The carbonyl conjugated double bond in the dienones 3a-c, 15a-d, and 32c,d undergoes chemoselective catalytic hydrogenation using piperidine and palladium-charcoal, affording the respective enones 4a-c, 16a-c, and 33c,d.