Studies On Catalytic Synthesis Of 2,5-Disubstituted Dihydropyridones

Aza Diels-Alder (ADA) reactions have been one of the cornerstone reactions in organic chemistry for the construction of nitrogen-containing six-membered rings and the formation of nitrogen-carbon bonds. While recent advances have been made in a number of Lewis acid-catalyzed aza Diels-Alder reactions in organic solvents and aqueous media, asymmetric versions using chiral catalysts have also been reported. Among these reactions imino dienophiles have different imino-nitrogen protecting groups including N-phosphoryl, N-tosyl, or N-aryl and alkyl, which can activate the imine towards the aza Diels-Alder reaction. While there is no effective catalytic research reported for the aza Diels-Alder reaction with N-benzhydryl imines as dienophiles, which have been widely used in Strecker (cyanation of imines) reaction with HCN or TMSCN affording the corresponding α-amino nitriles. In this dissertation, aza Diels-Alder reactions between N-benzhydryl imines and trans-1-methoxy-2-methyl-3-trimethylsiloxybuta-1,3 diene were systematically carried out catalyzed by Yb(OTf)3 to give 2,5-disubstituted 2,3-dihydro -4-pyridones in high yields. Three-component reactions of diene with aldehydes and amines were also performed smoothly to afford the desired cycloadducts under solvent-free condition in 51-86% yields. Several key factors including relationship betweenLewis acids and activity, solvents and catalyst loading have been discussed. A Diels-Alder mechanism based on experimental phenomena and studies has been proposed.Some chiral ligands include Schiff base ligands and Binol derivates were prepared and used for the asymmetric aza Diels-Alder reactions between diene and imines. Preliminary trials of the asymmetric reaction showed that (R)-Br-BINOL-Al was a promising system with moderate enantioselectivity and good reactivity.