Mannich Bases as Enone Precursors for Water-Mediated Efficient Synthesis of 2,3,6-Trisubstituted Pyridines and 5,6,7,8-Tetrahydroquinolines

Abstract

A highly efficient, regioselective and environmentally-friendly method has been developed for water mediated synthesis of 2,3,6-trisubstituted pyridines and 5,6,7,8-tetrahydroquinolines. The introduced method allows easy preparation of various polysubstituted pyridines and 5,6,7,8-tetrahydroquinolines via domino reaction of an enolizable ketone, ammonia and enones derived from different Mannich bases in mild reaction conditions. Montmorillonite K-10 promoted this one-pot three-component reaction and gave both new and known 2,3,6-trisubstituted pyridines and 5,6,7,8-tetrahydroquinolines in good yields. The reaction protocol provides a wide array of functionality in construction of polysubstituted pyridines and 5,6,7,8-tetrahydroquinolines from commercially available starting materials in easily applicable and environmentally-friendly conditions.

Progress in the Chemistry of Tetrahydroquinolines

“…A highly efficient water-mediated, three-component reaction was developed for the synthesis of polysubstituted pyridines and 5,6,7,8-tetrahydroquinolines. As shown in Scheme , the reaction between enolizable ketones 1439 , Mannich bases 1440 , and ammonium acetate afforded 5,6,7,8-tetrahydroquinolines 1441 in the presence of montmorillonite K-10 in water at 80 °C, in high yields (up to 96%) . Enone A , generated in situ from Mannich bases 1440 , and enamine B , arising form ketone 1439 and ammonium acetate, are the key intermediates for the formation of the target compounds.…”

“…Mannich bases 1440, and ammonium acetate afforded 5,6,7,8-tetrahydroquinolines 1441 in the presence of montmorillonite K-10 in water at 80 °C, in high yields (up to 96%) 608. Enone A, generated in situ from Mannich bases 1440, and enamine B, arising form ketone 1439 and ammonium acetate, are the key intermediates for the formation of the target compounds.Shang, Song, and co-workers developed a Yb(OTf) 3catalyzed four-component reaction for the synthesis of antimicrobial 5,6,7,8-tetrahydroquinolines (Scheme 392) 609.…”

An efficient water-mediated synthetic route for the alkylation of heteroarenes

“…Vinyl ketones are generally unstable and high-cost starting materials; therefore, we previously used Mannich bases as enone precursors. 21 Here, our strategy began with the reaction of 1 H -indole (3) with Mannich base 1a in water (Scheme 2). The reaction furnished target molecule 4a with quite a high yield (50%) under catalyst-free conditions.…”

Synthesis of Phosphorus(V)-Substituted Six-Membered N-Heterocycles: Recent Progress and Challenges

“…Hanashalshahaby and Unaleroglue [ 66 ] showed that pyridine-3-phosphonates 10 can be obtained by three-component oxidative coupling of diethyl (2-oxobutyl)phosphonate ( 8 ) with Mannich bases 9 and ammonium acetate ( 1 ) in the presence of catalyst K-10 ( Scheme 2 ). The product yields are reasonable both for aryl- and alkyl-substituted Mannich bases.…”