Studies towards the synthesis of trehalamine and the effect of adjacent chiral tertiary and quaternary centers on the metal-catalyzed allylic substitution reaction

Abstract

Studies were conducted towards advancing a trans-epoxy alcohol, derived from an amino-substituted cyclobutanone, to trehalamine. Efforts to manipulate the epoxy alcohol under standard conditions were hindered by the extraordinary propensity of the system to undergo the Payne rearrangement and the steric environment shielding both the hydroxyl group and the epoxide.

Metal-catalyzed allylic substitution reactions of allylic esters containing chiral quaternary and tertiary centers adjacent to the allyl system were examined. Reaction with stabilized nucleophiles led to exclusive attack at the less hindered allylic terminus and the stereoselectivity varied with the bidentate ligand used but favored retention. The yields and reaction times were improved with the use of microwaves. Application of standard conditions for transmetallation afforded starting material or decomposition. Conversely, vinyl and phenylstannatranes reacted cleanly and gave the opposite regio- and stereoselectivity than was observed with stabilized anions. Catalysts containing metals other than palladium were completely unreactive and led to recovered starting material.