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

Abstract

Keywords: Amino acids / Lactones / Michael additions / Synthetic methods / Radical reactionsAddition 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

Indium in Organic Synthesis

“…63,64 These have further been used in the synthesis of γ-aminoalkyl-substituted αmethylene γ-butyrolactones. 64,65,67 When the carbamate protection was replaced by a phthaloyl protection, the anti-product was formed predominantly, suggesting that no chelation was present in the transition state (…”

Formal Enantioselective Synthesis of (+)-Compactin

“…Michael addition of a vinyl copper reagent onto the less hindered top face ( re face) of the exocyclic ( Z )-α,β-unsaturated lactones 4a and 4b afforded the desired lactones 3a and 3b with diastereoselectivities of 6.4:1 and 6.7:1, respectively. The relative stereochemistry of the chiral center α to the lactone ( 3b ) was confirmed by NMR as a large NOE was observed between the allylic methine of the side chain with the proximal angular proton.…”