The a-hydroxyglycine 1 -readily accessible from glyoxylic acid hydrate and benzyl ~arbaminate[~I---was converted into the ethyl ether 2. Successive reaction with PCI3 and triethyl phosphite led to ethyl 2-benzyloxycarbonylamino-2-diethyloxyphosphorylacetate 3 (yield 80%). N-Acyl-2-(diethyloxyphosphoryl)glycine esters having various N-protecting groups are accessible by catalytic hydrogenolysis of the protecting group and acylation.
The phosphoryl ester 3 can be metalated by NaH in tetrahydrofuran (THF) and converted in high yields into Nbenzyloxycarbonyldehydroamino acid esters 6a -6d (Table 1) by condensation with aromatic aldehydes. Steric hindrance of the condensation by o-substituents is not observed. For the synthesis of aliphatic dehydroamino acid esters, metalation of 3 with lithium diisopropylamide and condensation with aliphatic aldehydes at -75 "C is the method of choice. By analogy, aromatic and aliphatic Ntert-butoxycarbonyldehydroamino acid esters are accessible from the phosphoryl ester 5 . The condensation products are formed as E/Z-mixtures and can be rearranged to afford mainly the (a-olefins.
The dehydroamino acid esters 6 can be catalytically hydrogenated to the corresponding amino acid esters in quantitative yield. Because of the very mild reaction conditions amino acids with acid-labile functional groups, such as e . g . 7 (yield from the corresponding aldehyde: 62%) can be synthesized in this way. The metalated phosphoryl esters 3 and 5 can also be smoothly C-alkylated, e.g. to 8.