A high yielding oxidation method for the preparation of substituted 2,3-dihydro-4-pyridones from 4-piperidones

Abstract

N-Alkyl substituted 4-piperidones readily undergo oxidation in high yield upon reaction with mercuric acetate. Application of the oxidation to the synthesis of the skeletal framework of several alkaloids is described.

Synthesis of 2,3-Dihydro-4-pyridones and 4-Pyridones by the Cyclization Reaction of Ester-Tethered Enaminones

“…2,3-Dihydro-4-pyridones are experimentally accessible via two main routes: chemical modification of a preformed nitrogen heterocycle and de novo construction of the heterocycle usually by the intramolecular cyclization of an acyclic intermediate. The first approach involves the addition of organometallic reagents to N -acyl salts of 4-methoxypyridine, developed by Comins,e.g., dehydrogenation of the corresponding saturated heterocycle, conjugate addition of the Grignard reagent on N -carbamoyl-4-pyridones, and reaction of 2,3-dihydropyran-4-ones with ammonia and primary amines . The second approach includes reactions of imines with dienes; cyclizations of primary amines with α,ß-unsaturated-1,3-diketones, dienones, and α-alkenoyl ketene dithioacetals; cyclizations of nitrogen-containing ynones; , reactions of amino esters with β-keto esters; [5 + 1] cycloaddition of N -formylmethyl-substituted tertiary enamides to isocyanides; [4 + 2] cycloaddition of 3-phenylcyclobutanones with nitriles; and cyclizations involving enaminones …”