Synthesis of 4‐Aryl‐8‐fluoro‐3a,4,5,9b‐tetrahydro‐3H‐cyclopenta[c]quinolines and Their Ozonides

Abstract

4-Aryl -8-fluoro-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolines are synthesized by acid-catalyzed (CF 3 CO 2 H) three-component cyclocondensation of 4-fluoroaniline with aromatic aldehydes and cyclopentadiene. Stable ozonides with (1R*,4S*,5aR*,6S*,11bS*)-configurations are obtained by ozonolysis of corresponding trifluoroacetyl derivatives.Introduction. -The tetrahydroquinoline skeleton is often used for the design of many synthetic compounds with diverse pharmacological properties. The fluorinated heterocyclic compounds possess a broad spectrum of biological activities [1] [2]. A special interest is focused on derivatives of 6-fluoroquinolines. Due to interesting chemical or biological properties of F-bearing tetrahydroquinolines, the synthesis of this class of azaheterocyclic compounds has attracted broad interest [3 -5].The aza-DielsÀAlder reaction (Povarov reaction; cyclocondensation of aromatic Schiff bases (anils) with electron-rich olefins) provides great opportunities in the formation of the quinoline skeleton [6] [7]. One-step three-component reaction of substituted anilines with aldehydes and cyclopentadiene as a dienophile is one of the synthetically most attractive approachs [8]. This method opens a simple route to the synthesis of substituted tetrahydroquinolines [9].Ozonolytic cleavage of the cycloalkenyl C¼C bond in tetrahydroquinoline fused with cyclopentene affords the ozonides of aza-heterocycles [10]. To improve antimalaria or antiviral activity of synthetic peroxides and ozonides, their conjugates containing weakly basic functional groups and heterocycles were obtained [11].Within this context, we report here a one-pot three-component cyclocondensation of 4-fluoroaniline with aromatic aldehydes and cyclopentadiene to synthesize 6fluorotetrahydroquinoline annulated with cyclopentene for the following possibility to obtain their stable ozonides.

Toward understanding the regioselectivity of the one‐pot reaction of phenylene diamines with aldehydes and cyclopentadiene (Povarov reaction). Combined experimental and theoretical approaches

“…The Lewis acid‐catalyzed reaction of Schiff bases with CPD or the alternative three‐component reaction of aromatic amine, aldehyde, and CPD catalyzed by trifluoroacetic acid selectively affords the endo , cis ‐isomer as the major product [13, 14]. In view of these data, the reactions involving p ‐ ( 1 ) and m ‐phenylenediamines ( 2 ), in which two ortho ‐positions around each amino group are vacant, are expected to give two regioisomeric bis‐adducts with a tetrahydroquinoline moiety exo ( endo )‐annulated to cyclopentene.…”