Internal activation of acrylate-type dienophiles for the Diels-Alder reaction. Stereoselective synthesis of conformationally constrained glutamate analogs

The [4+2] cycloaddition reaction of the unreactive acrylate-type dienophiles such as 5a and 6a was accomplished by introducing an electronegative or electron-withdrawing group as the ester counterpart. Among them, the pentafluorophenyl (PFP) group was found to be an excellent ester counterpart in view of its rate acceleration and chemical stability under the reaction conditions. The C-13 NMR spectral data of the dienophiles with the PFP group suggested that the conjugated CC-double bond was strongly polarized. The internal activation was found to be effective for the related dienophile or other dienes, in particular, unstable to Lewis acid catalysts. A successful application of this method is demonstrated by the syntheses of conformationally restricted analogs of L-glutamate, 3 and 4. (C) 1998 Elsevier Science Ltd. All rights reserved.