Ireland-Claisen Rearrangement - Michael Addition Sequence to δ-Amino Acids

Significance

Described is a one-pot route to optically active δ-amino acids 2 followed by a diastereoselective synthesis of piperidines 4 involving an Ireland-Claisen rearrangement and an asymmetric Michael addition from readily accessible trisubstituted olefins 1. Thus the Michael addition products 2, upon hydrogenolysis followed by in situ lactamization, gave the piperidin-2-ones 3 which, upon reduction, furnished the piperidines 4. Single diastereoisomers of 2 and 4 were obtained by column chromatography. A standard Ireland-Claisen rearrangement transition state allows rationalization of the stereochemical course of the process. Compounds 1 were prepared by the Baylis-Hillman reaction, then subsequent acetylation and isomerization using DABCO furnished the trisubstituted olefins 1 (P. H. Mason, N. D. Emslie Tetrahedron 1994, 50, 12001).