Synthesis of Chiral Tetrahydropyridines via a Three-Component Reaction

Significance

Described is the one-pot synthesis of chiral tetrahydro-7H-[1,3]oxazolo[3,2-a]pyridine derivatives 4a,b via a three-component condensation of acrolein (1), (S)-2-phenylglycinol (2) and 1,3-dicarbonyl compounds 3. The addition of molecular sieves to the reaction mixture was found to be crucial to reduce the formation of unwanted by-products. The desired tetrahydropyridines were isolated in moderate to good yields as inseparable mixtures of diastereoisomers. Reductive cleavage of the oxazolidine ring was demonstrated in one case to give 5 as a single isomer, which was assigned as (2R,3R) by ^¹H NMR spectroscopy. Although substrate scope with respect to the 1,3-dicarbonyl component was adequately examined, further examination of the aldehyde and amine components is desirable.