Synthesis of Highly Functionalized Amino Acid and Hydroxy Acid Derivatives from γ‐Aminoalkyl‐Substituted α‐Methylene‐γ‐butyrolactones

Abstract

Addition of C-, S-, N- and O-nucleophiles to α-amino acid derived α-methylene-γ-butyrolactones provided the corresponding Michael adducts. Addition of cuprates or cyanide, respectively, could be achieved with excellent selectivities. Addition of malonate anion or methoxide could be performed with good yields, but with rather poor selectivities. Addition of N-nucleophiles was achieved with N-benzylhydroxylamine. Further reductive cleavage of the hydroxy and the benzyl groups under hydrogenolytic conditions afforded a diaminocarboxylic acid derivative. Addition of S-nucleophiles furnished the corresponding 1,4 adducts in excellent yields and with good selectivities, especially when a cysteine derivative was used as nucleophile. Hydrogenation of the α-methylene-γ-butyrolactones provided α-methyl-substituted lactones, and ozonolysis yielded the corresponding α,β-dicarbonyl compounds. An isomerization of the exocyclic double bond to an endocyclic double bond was achieved with rhodium chloride as catalyst. The configurations of all products were established by X-ray crystallographic analyses and NMR spectroscopy, including NOE experiments.