The Friedlander reaction is the most commonly used method to synthesis substituted quinolines,
the essential intermediates in the medicine industry. A facile one-pot approach for synthesizing
substituted quinolines by the reaction of isoxazoles, ammonium formate-Pd/C, concentrated sulfuric
acid, methanol and ketones using Friedlander reaction conditions is reported. Procedures for the synthesis
of quinoline derivatives were optimized, and the yield was up to 90.4%. The yield of aromatic
ketones bearing electron-withdrawing groups was better than the ones with electron-donating substituents.
The structures of eight substituted quinolines were characterized by MS, IR, H-NMR and 13CNMR,
which were in agreement with the expected structures. The mechanism for the conversion was
proposed, which involved the Pd/C catalytic hydrogen transfer reduction of unsaturated five-membered
ring of isoxazole to produce ortho-amino aromatic ketones. Then the nucleophilic addition of with carbonyl
of the ketones generated Schiff base in situ, which underwent an intermolecular aldol reaction
followed by the elimination of H2O to give production of substituted quinolines. This new strategy can
be readily applied for the construction of quinolines utilizing a diverse range of ketones and avoids the
post-reaction separation of the o-amino aromatic ketone compounds. The conventionally used o-amino
aromatic ketone compounds in Friedlander reaction to prepare substituted quinoline are laborious to
synthesize and are apt to self-polymerize. While oxazole adopted in this work can be prepared at ease
by the condensation of benzoacetonitrile and nitrobenzene derivatives under the catalysis of a strong
base. Moreover, the key features of this protocol are readily available starting materials, excellent functional
group tolerance, mild reaction conditions, operational simplicity, and feasibility for scaling up.
Highly Enantioselective Phenylacetylene Addition to Aromatic Ketones Catalyzed by Cinchona Alkaloid—Aluminum Complexes.