Cyclizations using Selenium Chemistry for Substituted 3-Hydroxypiperidines and 3-Hydroxypyrrolidines

The development of new methods for the stereoselective synthesis of nitrogen heterocycles is of current interest because of increasing demands for the syntheses of biologically important alkaloids and related compounds. It is shown that selenium-induced cyclization of 4-hydroxy-5-pentenylamines occurs regio- and stereo-selectively to afford cis-3-hydroxy-2-phenylselenomethylpyrrolidines, whereas 5-hydroxy-6-hexenylamines cyclize and give trans-3-hydroxy-2-phenylselenomethylpiperidines, with some compounds forming stable hydrates. In all cases cyclization proceeds regioselectively to give only the exo adducts with moderate to good diastereoselectivity. The reaction appeared to be under kinetic control as product ratios did not alter with time and the separated diastereomers did not interconvert when resubjected to the reaction conditions. These phenylseleno-substituted compounds could be transformed to diols by substitution of the corresponding selenone with a hydroxide ion. Substituted pyrrolidines and piperidines were thus afforded from unsaturated protected amines by electrophilic activation with SeII, followed by oxidation of the intermediate to SeVI and substitution with nucleophiles.