Asymmetric Diels–Alder Cycloaddition of 1‐Aminocyclohexadiene to Chiral Acrylate: Synthesis of Enantiopure Bridgehead‐Aminobicyclo[2.2.2]octane‐2‐carboxylic Acid Derivatives

Abstract

AbstractThe acrylate derivative of the (R)‐4‐(3‐hydroxy‐4,4‐dimethyl‐2‐oxopyrrolidin‐1‐yl)benzoic acid benzyl ester (R)‐2 reacted with 1‐(benzyloxycarbonylamino)cyclohexadiene 3 under microwave irradation in solvent‐free conditions to yield [4+2] cycloadducts in good yields (91 %). The reaction proceeded with moderate endo selectivity (67 %) and good facial selectivity (90 %). The major cycloadducts were isolated and transformed to afford three enantiopure bicyclic β‐amino acids: (1S,2R,4R)‐1‐(benzyloxycarbonylamino)bicyclo[2.2.2]oct‐5‐ene‐2‐carboxylic acid [(1S,2R,4R)‐4], (1R,2R,4S)‐1‐(benzyloxycarbonylamino)bicyclo[2.2.2]oct‐5‐ene‐2‐carboxylic acid [(1R,2R,4S)‐5] and (R)‐1‐aminobicyclo[2.2.2]octane‐2‐carboxylic acid [(R)‐6]. This work has led to the preparation of these enantiopure bicyclic β‐amino acids and provides a rare example of an asymmetric Diels–Alder reaction by microwave activation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)