N,O Highly Regio‐ and Stereoselective Alkylation of Nucleophilic Glycine Equivalents with Carbonates of Allylic α‐Hydroxyphosphonates: A Convenient Route to Racemic 2‐Amino‐5‐phosphono‐4‐pentenoic Acids

Abstract

AbstractPalladium(0)‐catalyzed allylic alkylation of diethyl (acetyl‐amino)malonate (6), ethyl (diphenylmethyleneamino)acetate (7), and (diphenylmethyleneamino)acetonitrile (8), respectively, with the acrolein‐derived 1‐dialkoxyphosphinyl‐substituted carbonates 5 provides the γ‐substituted vinylphosphonates 9–11 in very good yields and with high regioselectivity. The stereochemical outcome is dependent on the mode of nucleophilic activation of the glycine equivalents 6–8: When the reactions are performed in the presence of N,O‐bis(trimethylsilyl)acetamide (BSA) the (Z) isomers (Z)‐9–(Z)‐11 are highly favoured, while in the absence of any additional activation of the nucleophiles the corresponding (E) isomers predominate. In the latter case, upon alkylation of the Schiff base derivatives 7 and 8, up to 30% of the α‐substitution products 12 and 13, respectively, are isolated as by‐products. The vinylphosphonates 9–11 are easily converted to the racemic 2‐amino‐5‐phosphono‐4‐pentenoic acids (Z)‐3 and (E)‐3, and to the saturated analogue 1.