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.
Three-component acid-catalyzed cyclocondensation of isomeric phenylenediamines with aldehydes and cyclopentadiene (CPD) was studied. In the M06-2X//B3LYP/6-311 + G(d,p) + IEFPCM(SMD) approximation, a quantum chemical model was developed, energies of the PES stationary points were determined, and activation barriers were found for the CPD addition to the protonated Schiff base (rate-limiting step) and for electrophilic carbocation cyclization to give endo, endo (syn)-or endo, exo (anti)-cyclopentene-annulated octahydropyridoquinoline-and octahydrophenanthroline-based cycloadducts.
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