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Catalyst and pressure dependent reductive cyclizations for the diastereo‐selective synthesis of hexahydropyrrolo[1,2‐ a ]quinoline‐5‐carboxylic esters
Author(s) -
Bunce Richard A.,
Schammerhorn James E.,
Slaughter Legrande M.
Publication year - 2006
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570430613
Subject(s) - chemistry , quinoline , reductive amination , hydroxylamine , catalysis , adduct , alkylation , ozonolysis , medicinal chemistry , hydrogen , amination , organic chemistry
A diastereoselective synthesis of 1,2,3,3a,4,5‐hexahydropyrrolo[1,2‐ a ]quinoline‐5‐carboxylic esters has been developed using a tandem reduction‐double reductive amination reaction. The nitro dicarbonyl cyclization substrates were synthesized by alkylation of methyl (2‐nitrophenyl)acetate with 2‐bromomethyl‐1,5‐hexadiene derivatives, followed by ozonolysis. Catalytic hydrogenation of each substrate gave the target heterocycle, along with a deacylated product and an adduct resulting from capture of the intermediate hydroxylamine by the side chain carbonyls. The product ratio varied dramatically with the catalyst and the hydrogen pressure. Cyclization to the title compounds was highly diastereoselective, producing each hexahydropyrrolo[1,2‐ a ]‐quinoline as a single stereoisomer with the all‐ cis geometry. The competing processes have not been observed in previous heterocyclization studies but can be attributed to greater strain in the system, which slows the final ring closure.