N,OHighly 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

Article abstract of DOI:10.1002/jlac.199719970722

Palladium(0)-catalyzed allylic alkylation of diethyl (acetylamino)malonate (6), ethyl (diphenylmethyleneamino)acetate (7), and (diphenylmethyleneamino)acetonitrile (8), respectively, with the acrolein-derived 1-dialkoxyphosphinyl-substituted carbonates 5 provides the α-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. VCH Verlagsgesellschaft mbH, 1997.